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Cigarette smoking and the risk of venous thromboembolism: The Tromso Study
Abstract
Background: Conflicting findings have been reported on the association between smoking and the risk of venous thromboembolism (VTE).
Objectives: To conduct a prospective, population-based cohort study to investigate the association between cigarette smoking and the risk of incident VTE.
Patients/Methods: Information on smoking habits was assessed by self-administered questionnaires in 24 576 subjects, aged 25–96 years, participating in the fourth Tromsø Study in 1994–1995. Incident cases of VTE were registered until the end of follow-up at 1 September 2007.
Results: A total of 389 incident VTE events (1.61 per 1000 person-years) were registered during follow-up (median of 12.5 years). Heavy smokers (> 20 pack-years) had a hazard ratio (HR) of 1.46 (95% confidence interval [CI] 1.04–2.05) for total VTE, and and an HR of 1.75 (95% CI 1.14–2.69) for provoked VTE, as compared with never smokers. The risk of provoked VTE increased with more pack-years of smoking (P = 0.02). Smoking was not associated with risk of unprovoked VTE. The number of pack-years was associated with increased risk of cancer and myocardial infarction, whereas the association between pack-years of smoking and VTE disappeared when failure times were censored at the occurrence of cancer or myocardial infarction.
Conclusions: Heavy smoking was apparently a risk factor for provoked VTE in analyses with VTE events as the only outcome. The lack of association between smoking and risk of VTE in analyses censored at the occurrence of cancer or myocardial infarction may suggest that smoking-attributable diseases or other predisposing factors are essential for smoking to convey a risk of VTE.
... Most prior studies among PWH with VTE are limited by the lack of adjudicated outcomes (which increase accuracy), have a small number of events, and were not focused on smoking and alcohol, particularly different patterns of use. Tobacco smoking has a wellknown association with arterial thrombosis in the general population and likely has a similar association with VTE [18][19][20][21][22][23][24]. Many studies of the general population have suggested that both former and current smokers have an increased risk of VTE [19,20,24]. ...
... Many studies of the general population have suggested that both former and current smokers have an increased risk of VTE [19,20,24]. The mechanisms underlying the association between smoking and VTE remain unclear, and may be complicated by long-term consequences of smoking such as myocardial infarction, chronic obstructive pulmonary disease, or cancer [21,25,26]. ...
... These are novel findings that identify potential risk factors that may increase VTE risk in PWH. We hypothesize that these findings may be explained by chronic vascular damage and subsequent comorbidities This study builds on studies in the general population which have suggested smoking is associated with VTE [19][20][21]23,24]. We demonstrated current smoking is associated with VTE among PWH, and former smoking was associated with VTE in a similar, but non-statistically significant manner. ...
Background
People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH.
Methods
We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time‐updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack‐years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency.
Results
During a median of 3.6 years of follow‐up, 213 PWH developed a VTE. One‐third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02–2.03) and former (HR: 1.44, 95% CI: 0.99–2.07) smokers compared to PWH who never smoked. Additionally, total pack‐years among ever‐smokers (HR: 1.10 per 5 pack‐years; 95% CI: 1.03–1.18) was associated with incident VTE in a dose‐dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11–1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE.
Conclusions
Current smoking and pack‐year smoking history were dose‐dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.
... Individual risk factors (RF, risk ratio, RR) for TED development used for calculations were taken from studies from the Czech Republic or Central Europe. Where several studies reported various values, mean values were used for calculation [21][22][23][24][25]. ...
... The risk of a TED event is up to 35× higher (mean value among studies 27.5×) than in the general population in women using OCs and up to 100× (mean 90×) higher in FV Leiden heterozygotes and homozygotes using OC, respectively [22,23]. As the FV Leiden heterozygote:homozygote ratio in the Czech population is approximately 30:1 [24], we can calculate with a weighted mean of the risk factor being 29.5. ...
... As the risk factors for women carrying mutation while using OC and smoking at the same time were not known, we used a simple additive calculation instead of synergistic action (thus, again, keeping at the conservative side of things). Risk factors for smokers were acquired from the study by Enga et al. [23]. In addition, we used simple arithmetic means where the results of several studies were available. ...
Background:
Thrombophilic mutations in genes for factor V Leiden and factor II prothrombin are among the most important risk factors for developing the thromboembolic disease (TED), along with the use of oral contraceptives (OCs) or smoking.
Aim:
This study aimed to investigate the occurrence of risk factors in young women using droplet digital PCR (ddPCR) and, based on the results of this investigation, to perform a cost-benefit analysis of ddPCR-based screening in young women starting to take OCs compared to the treatment costs of patients who develop preventable TED in the Czech Republic.
Methods:
In this cross-sectional study, female university students filled in a questionnaire and provided a blood sample for DNA isolation and ddPCR analysis of both aforementioned genetic risk factors. The results, along with data from literature and web search, were used for cost-benefit analysis valid for the Czech Republic.
Results:
Out of 148 participants, 30 (20%) were smokers and 49 (33%) took OCs. A mutation was confirmed in 6 women (4.1%) in the factor V gene and in 3 women (2%) in the factor II gene, respectively. A model calculation on a cohort of 50,000 women starting to use contraceptives in the Czech Republic every year showed that at maximum compliance, (i.e., non-use of OC and smoking cessation), screening could prevent 68 cases of TED over the course of the mean period of OC use (5.7 years). Economically, the costs of testing in this cohort (2.25 mil. USD) would be significantly lower than prevented treatment costs (16 mil. USD at maximum compliance); the cost-benefit break-even point would be at 14.1% compliance.
Conclusion:
The cost-benefit analysis based on our results indicates that screening for factor V Leiden and factor II prothrombin in young women before starting to use OCs would, in the conditions of the Czech Republic, likely be highly economically effective.
... Accordingly, astragalin may inhibit smoking-induced oxidative stress and block the MAPK signaling-inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism (Figure 8). The detrimental effects of cigarette smoking concerning cardiovascular diseases are well established [28,29]. However, the association between cigarette smoking and venous thromboembolism remains unclear. ...
... It has been reported that TF is the main initiator of the extrinsic coagulation pathway and plays a central role via producing proinflammatory cytokines, thereby initiating coagulation and downstream cellular signaling pathways [34,35]. This study showed that cigarette smoke enhanced the lung The detrimental effects of cigarette smoking concerning cardiovascular diseases are well established [28,29]. However, the association between cigarette smoking and venous thromboembolism remains unclear. ...
... The detrimental effects of cigarette smoking concerning cardiovascular diseases are well established [28,29]. However, the association between cigarette smoking and venous thromboembolism remains unclear. ...
Epidemiological evidence shows that smoking causes a thrombophilic milieu that may play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD) as well as pulmonary thromboembolism. The increased nicotine level induces a prothrombotic status and abnormal blood coagulation in smokers. Since several anticoagulants increase bleeding risk, alternative therapies need to be identified to protect against thrombosis without affecting hemostasis. Astragalin is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities of antioxidant and anti-inflammation. The current study investigated that astragalin attenuated smoking-induced pulmonary thrombosis and alveolar inflammation. In addition, it was explored that molecular links between thrombosis and inflammation entailed protease-activated receptor (PAR) activation and oxidative stress-responsive mitogen-activated protein kinase (MAPK)-signaling. BALB/c mice were orally administrated with 10–20 mg/kg astragalin and exposed to cigarette smoke for 8 weeks. For the in vitro study, 10 U/mL thrombin was added to alveolar epithelial A549 cells in the presence of 1–20 µM astragalin. The cigarette smoking-induced the expression of PAR-1 and PAR-2 in lung tissues, which was attenuated by the administration of ≥10 mg/kg astragalin. The oral supplementation of ≥10 mg/kg astragalin to cigarette smoke-challenged mice attenuated the protein induction of urokinase plasminogen activator, plasminogen activator inhibitor-1and tissue factor, and instead enhanced the induction of tissue plasminogen activator in lung tissues. The astragalin treatment alleviated cigarette smoke-induced lung emphysema and pulmonary thrombosis. Astragalin caused lymphocytosis and neutrophilia in bronchoalveolar lavage fluid due to cigarette smoke but curtailed infiltration of neutrophils and macrophages in airways. Furthermore, this compound retarded thrombin-induced activation of PAR proteins and expression of inflammatory mediators in alveolar cells. Treating astragalin interrupted PAR proteins-activated reactive oxygen species production and MAPK signaling leading to alveolar inflammation. Accordingly, astragalin may interrupt the smoking-induced oxidative stress–MAPK signaling–inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism.
... Previous studies with conflicting results have assessed the association between VTE and smoke [5,6,11,12]. In an old systematic review and meta-analysis of the literature by Ageno et al., smoke did not appear to be associated with a first episode of VTE [5]. ...
... In the Tromsø Study, information on smoking habits was assessed by self-administered questionnaires in 24.576 subjects aged 25-96 years [11]. After a mean follow-up of 12.5 years, heavy smoking was found to be a risk factor for provoked VTE in the analyses with VTE events as the only outcome, but the lack of association between smoking and VTE risk in the analyses censored at the occurrence of cancer [13] or myocardial infarction, suggests that smoking-attributable diseases or other predisposing factors are essential to convey a risk of VTE. ...
Background and Objectives: The influence of smoking habits on mortality, VTE recurrence, and major bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated. Materials and Methods: We used data from the RIETE (Registro Enfermedad TromboEmbólica) registry to compare mortality, VTE recurrence, and major bleeding risk in smoking versus non-smoking patients with acute VTE. Results: 50,881 patients (43,426 non-smoking and 7455 smoking patients) were included. After a median follow-up of 8.8 months, 7110 patients died (fatal PE 292 and fatal bleeding 281), 3243 presented VTE recurrence, and 1579 had major bleeding. At multivariate analysis, smoking behavior was associated with a higher hazard of death, (HR: 1.28; 95% CI: 1.19–1.40). The risk of VTE recurrence was marginally increased in smoking patients compared to non-smoking patients (1.14; 95% CI: 1.02–1.27). Major bleeding did not differ in smoking and non-smoking patients (1.15; 95% CI: 0.96–1.38). The presence of cancer did not appear to influence the association between smoking habits and death (HR: 1.34; 95% CI: 1.22–1.47 in cancer patients and HR: 1.23; 95% CI: 1.04, 1.45 in non-cancer patients, respectively) Conclusions: the risk of death after an acute episode of VTE appeared to be higher in smoking than in non-smoking patients and this risk is higher between patients presenting PE at the onset of symptoms.
... However, smoking was not a risk factor for delayed VTE prescription (data not shown). Smoking is contentious as a cause of VTE, with studies suggesting that it may be a confounding factor and that comorbid conditions such as malignancy may increase risk of VTE [19,20]. While this debate is outside the scope of this paper, previous literature has suggested that a history of heavy smoking is a risk factor for VTE only in patients with other antecedent major risk factors, a subset which would include patients in this study [20]. ...
... Smoking is contentious as a cause of VTE, with studies suggesting that it may be a confounding factor and that comorbid conditions such as malignancy may increase risk of VTE [19,20]. While this debate is outside the scope of this paper, previous literature has suggested that a history of heavy smoking is a risk factor for VTE only in patients with other antecedent major risk factors, a subset which would include patients in this study [20]. ...
The aim of this study was to describe the timing of venous thromboembolism diagnosis in patients with severe burns and determine the relationship between venous thromboembolism prophylaxis and venous thromboembolism development in a large trauma hospital. A retrospective cohort study over 10 years from 2009 to 2019 was conducted. Records of 226 patients with >20% total body surface area burns were surveyed, and 20 patients with symptoms suggestive of venous thromboembolism had a diagnosis of VTE confirmed on imaging. Enoxaparin was the most common primary thromboprophylaxis (85%, n = 192), followed by heparin (13.71%, n = 31) and sequential compression devices (0.88%, n = 2). Compared with patients who did not develop a venous thromboembolism, patients who developed a venous thromboembolism had a mean difference in time from admission to thromboprophylaxis prescription of 1.72 days (95% CI = −1.50 to 4.92, p > 0.05) and 10.51 days in those who developed a pulmonary embolus (mean difference = 10.51, 95% CI = 3.73 to 17.32, p = 0.0006). A threshold of 4 days was identified by which 96% of patients who never developed venous thromboembolism during admission were prescribed prophylaxis, compared with 32% of those who developed a pulmonary embolus. No bleeding or adverse events were recorded. Timely prescription of thromboprophylaxis in patients with severe burns is critical in reducing venous thromboembolism incidence. Avoidance of delay post injury is especially critical in preventing venous thromboembolism development. Guidelines on thromboprophylaxis must be considered on an individualised patient basis, considering likely surgical requirements and obesity.
... Additionally, our patient has a smoking history of 30 pack years. Smoking is originally known as a major risk factor for VTE; however, a cohort study conducted in the municipality of Tromsø, Norway, by Enga et al. in 2008, which included 24,576 participants, revealed that there should be an additional predisposing factor for smoking to convey a risk of VTE; this includes cancer or smoking-related diseases [20]. ...
Multiple myeloma patients are recognized to have a higher risk of venous thrombosis. The cause of this could be attributed to several risk factors, such as circulating prothrombotic microparticles, disease-specific variables, and alterations in coagulation and fibrinolysis factors. Recent research has revealed that these individuals also experience greater arterial thrombosis, including acute myocardial infarction and stroke. In this case report, we present the clinical profile and management of a 42-year-old patient who presented with signs and symptoms of deep venous thrombosis (DVT) and was diagnosed with multiple myeloma. The aim of this case report is to highlight a rare clinical presentation and diagnostic workup in a patient with multiple myeloma. Additionally, we discuss the possible factors provoking the development of DVT as a first presentation before treatment initiation and their possible mechanisms.
... TEV poate fi privit ca parte a continuumului bolilor cardiovasculare, iar factorii de risc comuni -cum ar fi fumatul, obezitatea, hipercolesterolemia, hipertensiunea arterială și diabetul zaharat [8] își împart contribuţia cu boală arterială, în special ateroscleroza [9]. Cu toate acestea, cel puţin în parte, acest lucru poate fi o asociere indirectă, mediată de efectele bolii coronariene și, în cazul fumatului de cancer [10,11]. Infarctul miocardic și insuficienţă cardiacă cresc riscul de EP [12]. ...
The purpose of the study was to present a clinical case of pulmonary embolism in a young patient of 26 years, with a brief review of the literature. The particularity of the presented case with the pulmonary embolism was the association with the acute thrombosis of the deep venous system venous system on background of combined oral contraceptives use.
... This thought origina ted from studies revealing clots in histopathologic examinations of CCM 27,28 , as well as probable protective factor of antithrombotic therapy in such patients 6,28 . Nicotine has been shown to increase the risk of stroke and venous thrombosis 29,30 . The same risk has been also previous ly discussed in patients suffering from diabetes 31,32 . ...
Background and purpose:
Investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period.
Methods:
We performed a retrospective review of our CM institutional database spanning from 2003 to 2021.
Inclusion criteria:
non-missing serial magnetic resonance imaging (MRI) studies and clinical baseline metrics such as vascular risk factors.
Exclusion criteria:
Patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10-year) of hemorrhage.
Results:
89 patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10-years of follow-up in patients using nicotine (HR: 2.11 [95% CI, 0.86-5.21]), and patients with diabetes (HR: 3.25 [95% CI, 0.71-14.81]). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risk of bleeding was observed: arterial hypertension = 42.9% (18.8%- 70.4%); diabetes = 66.7% (12.5%-98.2%); hyperlipidemia = 30% (8.1%-64.6%); active nicotine abuse = 50% (24.1%-76%); and obesity = 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%- 41.1%).
Conclusions:
The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.
... A metanalysis that included participants without cardiovascular disease or VTE at baseline showed that current smoking was associated with an increased VTE risk (HR 1.38 95%CI, 1.20-1.58). The HR remained similar after excluding patients diagnosed with cancer [57], that is, in contrast with previous studies linking excess VTE risk to an increased hospitalization for smoking-related diseases, including cancer [58,59]. A more recent metanalysis has shown that current smoking was significantly associated with VTE prevalence in case-control studies (OR 1.34, 95%CI, 1.01-1.77), ...
Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.
... Smoking is a risk factor for VTE as well as other cardiovascular events, therefore, smoking cessation should be advised in IRDs. 108 The use of estrogen-containing oral contraceptive pills should be avoided in those female patients with IRDs at a high risk of developing VTE. 109 SUMMARY VTE risk is increased in most IRDs, based on data from systematic reviews or from individual observational studies. ...
Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a cardiovascular event whose risk is increased in most inflammatory rheumatic diseases (IRDs). Mechanisms that increase VTE risk include antiphospholipid antibodies (APLs), particularly anticardiolipin antibodies, anti-beta2glycoprotein I antibodies and lupus anticoagulant present together, and inflammation-mediated endothelial injury. Patients with IRDs should receive long-term anticoagulation drugs when the risk of VTE recurrence is high. In the light of recent warnings from regulatory agencies regarding heightened VTE risk with Janus kinase inhibitors, these drugs should be initiated only after a careful assessment of VTE risk in those with IRDs.
... and 1.08 (95% CI 0.90-1.29), respectively 13 , with similar findings in other studies 8,121 . The stronger association between smoking and provoked VTE might be explained by the well-known association between smoking and numerous health conditions (such as cancer, respiratory illnesses, myocardial infarction and stroke), which can lead to hospitalization and/or immobilization. ...
Venous thromboembolism, that consists of the interrelated conditions deep-vein thrombosis and pulmonary embolism, is an under-appreciated vascular disease. In Western regions, approximately 1 in 12 individuals will be diagnosed with venous thromboembolism in their lifetime. Rates of venous thromboembolism are lower in Asia, but data from other regions are sparse. Numerous risk factors for venous thromboembolism have been identified, which can be classified as acute or subacute triggers (provoking factors that increase the risk of venous thromboembolism) and basal or acquired risk factors (which can be modifiable or static). Approximately 20% of individuals who have a venous thromboembolism event die within 1 year (although often from the provoking condition), and complications are common among survivors. Fortunately, opportunities exist for primordial prevention (prevention of the development of underlying risk factors), primary prevention (management of risk factors among individuals at high risk of the condition) and secondary prevention (prevention of recurrent events) of venous thromboembolism. In this Review, we describe the epidemiology of venous thromboembolism, including the incidence, risk factors, outcomes and opportunities for prevention. Meaningful health disparities exist in both the incidence and outcomes of venous thromboembolism. We also discuss these disparities as well as opportunities to reduce them.
... Categorization as minor and major provoking risk factors was based on the guidance provided by the International Society on Thrombosis and Haemostasis (ISTH) [36]. In addition to the ISTH-based criteria, the presence of an intravenous catheter [37] and May-Thurner syndrome (>70% iliofemoral compression) [38] were categorized as major risk factors, whereas immobilization > 4 h [39] and heavy smoking (>20 pack years) [40] as minor risk factors. VTE in the presence of merely an environmental risk factor (male sex and older age) was categorized as unprovoked thromboembolism. ...
(1) Background: Thrombophilia testing utility has remained controversial since its clinical introduction, because data on its influence on treatment decisions are limited. (2) Methods: We conducted a single-center retrospective cohort study of 3550 unselected patients referred for thrombophilia consultation at the Bern University Hospital in Switzerland from January 2010 to October 2020. We studied the influence of thrombophilia testing results on treatment decisions and evaluated the association between thrombophilia and thromboembolic and pregnancy-related morbidity events after testing up to 03/2021. (3) Results: In 1192/3550 patients (34%), at least one case of thrombophilia was found and 366 (10%) had high-risk thrombophilia. A total of 211/3550 (6%) work-ups (111/826 (13%) with low-risk thrombophilia and 100/366 (27%) with high-risk thrombophilia) led to an appropriate decision to extend or initiate anticoagulation, and 189 (5%) negative results led to the withholding of anticoagulation therapy inappropriately. A total of 2492 patients (69%) were followed up for >30 days, with a median follow-up of 49 months (range, 1–183 months). Patients with high-risk thrombophilia had a higher risk of subsequent venous thromboembolic events and pregnancy-related morbidity compared to those without thrombophilia. (4) Conclusions: Our study demonstrated the limited usefulness of thrombophilia work-up in clinical decision-making. High-risk thrombophilia was associated with subsequent venous thromboembolism and pregnancy-related morbidity.
... 28 Within this study, there was no increase in d-dimer levels noted, even with active or previous smokers being a significant characteristic within our baseline population. 29 It is important to note some biochemistry data such as the limited increase of total cholesterol in patients treated with raloxifene 60 mg, that could be correlated with the medication's agonistic action at ERs within adipose tissues, leading to protection against a possible increased risk for vascular accidents. 30 This study presents several limitations that deserve acknowledgement. ...
Background
Current available therapeutic options for Coronavirus Disease-2019 (COVID-19) are primarily focused on treating hospitalized patients, and there is a lack of oral therapeutic options to treat mild to moderate outpatient COVID-19 and prevent clinical progression. Raloxifene was found as a promising molecule to treat COVID-19 due to its activity to modulate the replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and act as an immunomodulator to decrease proinflammatory cytokines.
Methods
This was a phase 2 multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of raloxifene in adult patients with mild to moderate COVID-19 between October 2020 to June 2021 in five centers located in Italy. This was a planned 2/3 adaptive study, but due to operational difficulties, the study was discontinued during the phase 2 study segment. Participants were randomized 1:1:1 to receive oral placebo, raloxifene 60 mg, or raloxifene 120 mg by self-administration for a maximum of two weeks. The primary outcomes were the proportion of patients with undetectable SARS-CoV-2 via nasopharyngeal swabs at day 7 and the proportion of patients who did not require supplemental oxygen therapy or mechanical ventilation on day 14. Safety was assessed. The trial is registered (EudraCT 2021–002,476–39, and ClinicalTrials.gov: NCT05172050).
Findings
A total of 68 participants were enrolled and randomized to placebo (n = 21), raloxifene 60 mg (n = 24), and raloxifene 120 mg (n = 23). The proportion of participants with undetectable SARS-CoV-2 after seven days of treatment with raloxifene 60 mg [36.8%, 7/19 vs. 0.0%, 0/14] and 120 mg [22.2%, 4/18 vs. 0.0%, 0/14] was better compared to placebo, [risk difference (RD) = 0·37 (95% C.I.:0·09–0·59)] and [RD = 0·22 (95% C.I.: -0·03–0·45)], respectively. There was no evidence of effect for requirement of supplemental oxygen and/or mechanical ventilation with effects for raloxifene 60 mg and raloxifene 120 mg over placebo, [RD = 0·09 (95% C.I.: -0·22–0·37)], and [RD = 0·03 (95% C.I.: -0·28–0·33)], respectively. Raloxifene was well tolerated at both doses, and there was no evidence of any difference in the occurrence of serious adverse events.
Interpretation
Raloxifene showed evidence of effect in the primary virologic endpoint in the treatment of early mild to moderate COVID-19 patients shortening the time of viral shedding. The safety profile was consistent with that reported for other indications. Raloxifene may represent a promising pharmacological option to prevent or mitigate COVID-19 disease progression.
Funding
The study was funded by Dompé Farmaceutici SpA and supported by the funds from the European Commission – Health and Consumers Directorate General, for the Action under the Emergency Support Instrument- Grant to support clinical testing of repurposed medicines to treat SARS-COV-2 patients (PPPA-ESI-CTRM-2020-SI2.837140), and by the COVID-2020–12,371,675 Ricerca finalizzata and line 1 Ricerca Corrente COVID both funded by Italian Ministry of Health.
... Это и курение, и ожирение, и сахарный диабет, и дислипидемии, и артериальная гипертония. Некоторые авторы предлагают рассматривать ТЭЛА как часть континуума сердечнососудистой патологии, поскольку существует прямая взаимосвязь между увеличением частоты ВТЭ у пациентов с ИМ и сердечной недостаточностью, и наоборот, у пациентов с легочными эмболиями повышены риски развития ИМ и инсультов [10][11][12][13]. ...
The prevalence and mortality due to venous thromboembolism (VTE) occupies a leading position among the population throughout the world. The incidence and severity of VTE increases the older the patient. The emergence of a new group of direct oral anticoagulants significant changed the management of these groups of patients. The article touches upon the problem of choice, efficacy and safety of oral anticoagulants in elderly and senile patients with VTE, in particular in pulmonary embolism (PE). An analysis of randomized clinical trials and prospective cohort studies is given. In addition, rational recommendations are given on the optimal choice of oral anticoagulant in these categories of patients. Apixaban and rivaroxaban are highly effective drugs of choice with a reliable safety profile in patients of the senile age group in the prevention and treatment of VTE, including PE, and apixaban has the most optimal profile and safety class among all other oral anticoagulants when used in elderly and senile patients.
... Additionally, the risk of PE increases 6-fold among obese individuals compared with normal weight individuals (19). VTE risk is 1.3-1.7 times higher among current cigarette smokers than among non-smokers (20)(21)(22). Similarly, cigarette smoking was related to an absolute risk increase of 24.3 VTE cases per 100,000 person/year (22). ...
Background: Interactions between genetic and environmental risk factors (GxE) contribute to an increased risk of venous thromboembolism (VTE). Understanding how these factors interact provides insight for the early identification of at-risk groups within a population and creates an opportunity to apply appropriate preventive and curative measures.
Objective: To estimate and compare GxE for VTE risk in the general Hungarian and Roma populations.
Methods: The study was based on data extracted from a database consisting of results previously obtained from a complex health survey with three pillars (questionnaire-based, physical, and laboratory examinations) involving 406 general Hungarian and 395 Roma subjects. DNA was genotyped for rs121909567 (SERPINC1), rs1799963 (F2), rs2036914 (F11), rs2066865 (FGG), rs6025 (F5), and rs8176719 (ABO) polymorphisms. After allele frequency comparisons, the odds ratio (OR) was calculated for individual SNPs. Furthermore, genetic risk scores (weighted GRS, unweighted GRS) were computed to estimate the joint effect of the genetic factors. Multivariable linear regression analysis was applied to test the impact of GxE on VTE risk after interaction terms were created between genetic and VTE risk factors [diabetes mellitus (DM), cancer, chronic kidney diseases (CKD), coronary artery diseases (CAD), migraine, depression, obesity, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein (HDL-C), triglyceride (TG), and smoking].
Results: Interestingly, the rs121909567 (SERPINC1, ATBp3 mutation) SNP was not present in the general population at all. However, the risk allele frequency was 1% among the Roma population, which might suggest a founder effect in this minority. This polymorphism multiplicatively interacted with CAD, CKD, cancer, DM, depression, migraine, and obesity. Even though interactions were not statistically significant, the trend of interaction showed the probability of an incremental VTE risk among the Roma population. The risk of VTE was 4.7 times higher ( p > 0.05) for Roma subjects who had ≥3 wGRS (median value) compared with individuals having lower wGRS values but lower for the general subjects (OR = 3.1 × 10 ⁻⁸ ). Additionally, the risk of VTE was 6.6 times higher in the Roma population that had ≥3 risk alleles (median value) than in individuals with the 0–1 risk allele, and the overall risk was much higher for the Roma population (OR = 6.6; p > 0.05) than for the general Hungarian population (OR = 1.5; p > 0.05). Five positive and significant GxE interactions were identified in the Roma population. The risk of VTE was higher among depressive Roma subjects who carried the risk variant rs2036914 (β = 0.819, p = 0.02); however, this interaction was not significant for the general subjects. The joint presence of high levels of LDL-C and rs2066865 (FGG) increased the VTE risk only among Roma individuals (β = 0.389, p = 0.002). The possibility of VTE risk increment, as a result of a multiplicative interaction between rs8176719 (ABO) and cancer, was identified, which was higher for the Roma population (β = 0.370, p < 0.001) than for the general population (β = −0.042, p = 0.6). The VTE risk increased in the Roma population (β = 0.280, p = 0.001), but was higher in the general population (β = 0.423, p = 0.001) as a result of the multiplicative interaction between CAD and rs2036914 (F11). The presence of a multiplicative interaction between rs2066865 (FGG) and CAD increased the VTE risk for the Roma population (β = 0.143, p = 0.046) but not for the general population (β = −0.329, p < 0.001).
Conclusions: rs121909567 (SERPINC1, ATBp3) was confirmed as a founder mutation in the Roma population. Our study revealed some evidence on the burden of the joint presence of genetic and environmental risk factors on VTE, although the finding is highly subjected to the selection and observational biases due to the very small number of VTE cases and the observational nature of the study design, respectively. As a result of higher genetic load and GxE interactions, this minority Roma population is at higher risk of VTE than the general Hungarian population. Thus, our results suggest the need for an intensive search for the rs121909567 (SERPINC1; ATBp3) founder mutation, which might be an important factor for the assessment of thrombotic disease susceptibility among the Roma population. In addition, we strongly recommend further studies among a large number of VTE cases to explore the more precise impact of genetic and environmental risk factors on VTE in the study populations.
... [10] Only 6 patients had a ≥20 packs-a-year smoking history. Smoking has been shown to be a risk factor for VTE [58,59] in conjunction with other risk factors such as HIV. [5] Seven patients in our present study were diagnosed with a malignant process, 5 of whom had HIVrelated Kaposi sarcoma (8.5% of HIV-positive group). ...
Background:
HIV and tuberculosis (TB) independently cause an increased risk for venous thromboembolic disease (VTE): deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Data from high HIV and TB burden settings describing VTE are scarce. The Wells' DVT and PE scores are widely used but their utility in these settings has not been reported on extensively.
Objectives:
To evaluate new onset VTE, compare clinical characteristics by HIV status, and the presence or absence of TB disease in our setting. We also calculate the Wells' score for all patients.
Methods:
A prospective cohort of adult in-patients with radiologically confirmed VTE were recruited into the study between September 2015 and May 2016. Demographics, presence of TB, HIV status, duration of treatment, CD4 count, viral load, VTE risk factors, and parameters to calculate the Wells' score were collected.
Results:
We recruited 100 patients. Most of the patients were HIV-infected (n=59), 39 had TB disease and 32 were HIV/TB co-infected. Most of the patients had DVT only (n=83); 11 had PE, and 6 had both DVT and PE. More than a third of patients on antiretroviral treatment (ART) (43%; n=18/42) were on treatment for <6 months. Half of the patients (51%; n=20/39) were on TB treatment for <1 month. The median (interquartile range (IQR)) DVT and PE Wells' score in all sub-groups was 3.0 (1.0 - 4.0) and 3.0 (2.5 - 4.5), respectively.
Conclusion:
HIV/TB co-infection appears to confer a risk for VTE, especially early after initiation of ART and/or TB treatment, and therefore requires careful monitoring for VTE and early initiation of thrombo-prophylaxis.
... However, other studies have reported an increased risk of VTE among current and formers smokers 13 , among current smokers only 14,15 , and among heavy smokers only [16][17][18][19] . Furthermore, some studies have reported an association only between smoking and provoked VTE 21,43 . The diverging results could be attributed to differences in the distribution of patients with cancer and other co-morbid conditions associated with VTE. ...
Smoking is a well-established risk factor for cancer, and cancer patients have a high risk of venous thromboembolism (VTE). Conflicting results have been reported on the association between smoking and risk of VTE, and the effect of smoking on VTE-risk in subjects with cancer is scarcely studied. We aimed to investigate the association between smoking and VTE in subjects with and without cancer in a large population-based cohort. The Scandinavian Thrombosis and Cancer (STAC) cohort included 144,952 participants followed from 1993–1997 to 2008–2012. Information on smoking habits was derived from self-administered questionnaires. Active cancer was defined as the first two years following the date of cancer diagnosis. Former smokers (n = 35,890) and those with missing information on smoking status (n = 3680) at baseline were excluded. During a mean follow up of 11 years, 10,181 participants were diagnosed with cancer, and 1611 developed incident VTE, of which 214 were cancer-related. Smoking was associated with a 50% increased risk of VTE (HR 1.49, 95% CI 1.12–1.98) in cancer patients, whereas no association was found in cancer-free subjects (HR 1.07, 95% CI 0.96–1.20). In cancer patients, the risk of VTE among smokers remained unchanged after adjustment for cancer site and metastasis. Stratified analyses showed that smoking was a risk factor for VTE among those with smoking-related and advanced cancers. In conclusion, smoking was associated with increased VTE risk in subjects with active cancer, but not in those without cancer. Our findings imply a biological interaction between cancer and smoking on the risk of VTE.
... [19][20][21] Although previous studies have identified smoking as a potential risk factor for VTE in adult patients with comorbidities, it was not significantly associated with VTE development in this study. 22 Insufficient time for smoking to have increased coagulative risk could explain the lack of association in this study's pediatric population, and the NTDB does not provide pack-year data to probe this hypothesis further. Age, sex, race, ethnicity, and insurance status were all found to have no significant association with VTE development within our cohort. ...
OBJECTIVE
Venous thromboembolism (VTE) can cause significant morbidity and mortality in hospitalized patients, and may disproportionately occur in patients with limited mobility following spinal trauma. The authors aimed to characterize the epidemiology and clinical predictors of VTE in pediatric patients following traumatic spinal injuries (TSIs).
METHODS
The authors conducted a retrospective cohort analysis of children who experienced TSI, including spinal fractures and spinal cord injuries, encoded within the National Trauma Data Bank from 2011 to 2014.
RESULTS
Of the 22,752 pediatric patients with TSI, 192 (0.8%) experienced VTE during initial hospitalization. Proportionally, more patients in the VTE group (77%) than in the non-VTE group (68%) presented following a motor vehicle accident. Patients developing VTE had greater odds of presenting with moderate (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.4–4.8) or severe Glasgow Coma Scale scores (aOR 4.3, 95% CI 3.0–6.1), epidural hematoma (aOR 2.8, 95% CI 1.4–5.7), and concomitant abdominal (aOR 2.4, 95% CI 1.8–3.3) and/or lower extremity (aOR 1.5, 95% CI 1.1–2.0) injuries. They also had greater odds of being obese (aOR 2.9, 95% CI 1.6–5.5). Neither cervical, thoracic, nor lumbar spine injuries were significantly associated with VTE. However, involvement of more than one spinal level was predictive of VTE (aOR 1.3, 95% CI 1.0–1.7). Spinal cord injury at any level was also significantly associated with developing VTE (aOR 2.5, 95% CI 1.8–3.5). Patients with VTE stayed in the hospital an adjusted average of 19 days longer than non-VTE patients. They also had greater odds of discharge to a rehabilitative facility or home with rehabilitative services (aOR 2.6, 95% CI 1.8–3.6).
CONCLUSIONS
VTE occurs in a low percentage of hospitalized pediatric patients with TSI. Injury severity is broadly associated with increased odds of developing VTE; specific risk factors include concomitant injuries such as cranial epidural hematoma, spinal cord injury, and lower extremity injury. Patients with VTE also require hospital-based and rehabilitative care at greater rates than other patients with TSI.
... VTE can be considered as a part of cardiovascular continuum, as classic risk factors -smoking, obesity, hypercolesterolaemia, hypertension and diabetes mellitus (10,11) -are also risk factors for atherosclerotic disease (12). Yet, it may be the cause of an indirect association through the complications of ischemic coronary disease and, regarding smoking, through neoplasia (13). The recent myocardial infarction and heart failure increase the PE risk (14). ...
The pulmonary embolism (PE) represents a medical condition with increasing incidence. The various clinical forms of PE have different prognosis, related to the presence of markers of right ventricle (RV) dysfunction (biochemical or imagistic). Material and method. In this study we included 82 consecutive patients with intermediate-high risk PE, assessing the main risk factors distribution. We divided the patients in two groups, study group - receiving thrombolytic therapy (ateplase (t-Pa)) associated to anticoagulation (unfractionated heparin (UFH)) – and control group – receiving anticoagulation alone -. The inclusion in study group was indicated by the high bleeding risk, in this group being included patients without contraindications for thrombolysis, patients without severe renal dysfunction and patients with body mass index (BMI) 18.5-29.9 kg/m2. We assessed the gender distribution in the two groups, the medium age distribution and the main PE risk factors in the two groups. Also, we assessed the effect of the both therapies on the hemodynamic instability rate on 7 day from admission (defined by systolic blood pressure (SBP) < 100 mmHg or a SBP drop >40 mmHg from inclusion value). The statistical analysis was made using SPSS program, by comparing the association between risk factors and the two groups, by Chi-squared test, while the gender and age distribution was made using the Shapiro Wilk test for the evenly data distribution and Wilk test (as the data were unevenly distributed). Results. We found no correlation between the risk factors and the study groups. There was no statistical significance regarding the gender distribution, but the medium age was higher in control group (61.82 y.o vs. 71.28 y.o, p < 0.001. Regarding the hemodynamic instability rate the Chi-squared test proved a statistical significant higher incidence in the control group (p = 0.03).
... In this study, we observed no association between smoking, and the risk of VTE. This is in opposition to previous studies [43,44] including the large UK biobank study that observed convincing associations between smoking and the risk of VTE [9]. A previous metaanalysis [7] of 32 observational studies has shown that smoking is associated with an increased risk of VTE, with a risk ratio of 1.19 as well as linear responses from pack-years and cigarettes per day. ...
Background
Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI.
Methods
We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism.
Results
During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI.
Conclusions
Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.
... Although we found no significant link in the univariate analysis between current smoking and postoperative DVT (p = 0.095), this association was strengthened with further adjustment for potential confounders in the multivariate logistics regression model, which suggested that smoking was independently associated with DVT in patients undergoing surgery for FSF, with a 2.9-fold elevated risk of DVT in smokers compared with nonsmokers. Previous investigations on the relationship between smoking and DVT were inconsistently reported and greatly varied [18,19], while smoking has been shown to act synergistically with other predisposing factors (e.g., cancer, older age, cardiovascular diseases) in the development of the provoked DVT [20,21]. In addition, it has been well-established that cigarette smoking was significantly associated with high plasma fibrinogen levels, leading to prolonged coagulation propensity [22,23]. ...
Background
There is still a lack of data on deep vein thrombosis (DVT) following surgically treated femoral shaft fracture (FSF). The goal of this study was to investigate the characteristics of postoperative DVT and the association between the occurrence of DVT and risk factors in patients undergoing surgical treatment for FSF.
Methods
This observational retrospective case-control study reviewed 308 patients who received surgical treatment of FSF between January 2016 and October 2020 at a university hospital. Univariate analyses were performed on the data of demographics, comorbidities, laboratory biomarkers, and operation-related indexes. The receiver operating characteristic (ROC) curve analysis, univariate analyses, and multivariate logistic regression analysis were employed to identify the independent risk factors associated with DVT.
Results
In total, 308 patients with surgically treated FSF were included, among whom 48 (15.6%) patients had postoperative DVTs. The univariate analyses showing significant differences regarding DVT were American Society of Anesthesiologists (ASA) classification, diabetes mellitus, current smoking, aspartate transaminase (AST), and very-low-density lipoprotein (VLDL) level among the 34 factors. According to the ROC results, the optimal cutoff values for intraoperative blood loss, d -dimer, and age were 350 ml, 1.08 μg/ml, and 35 years, respectively. The multivariable model demonstrated 4 significantly independent associations with postoperative DVT, including current smoking, intraoperative blood loss (> 550 ml), age (> 35 years), and d -dimer > 1.09 μg/ml.
Conclusion
These risk factors as screening tools contribute to risk stratification of the occurrence of thromboembolic events. In addition, our findings would help orthopedic surgeons make a cross-specialty decision and implement targeted precaution measures for patients with FSF.
... In this study, we observed no association between smoking, and the risk of VTE. This is in opposition to previous studies 43, 44 including the large UK biobank study that observed convincing associations between smoking and the risk of VTE 9 . A previous meta-analysis 7 of 32 observational studies has shown that smoking is associated with an increased risk of VTE, with a risk ratio of 1.19 as well as linear responses from pack-years and cigarettes per day. ...
Background
Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI.
Methods
We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism.
Results
During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1,000 PY. This included 505 cases of pulmonary embolism and 1,144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI.
Conclusions
Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism. Hypertension, dyslipidaemia and diabetes should not be considered risk-factors for venous thromboembolism.
... Já o modelo B, com a não inclusão da variável 'instituição notificadora', permitiu observar que, de fato, acentuou-se a associação das comorbidades com o óbito, conforme relatos de outros estudos. 10,11 Percebe-se que não foi o fato de estar internado em uma instituição pública ou privada que determinou o desfecho 'óbito' e sim as condições prévias à entrada no sistema de saúde, entre as quais as comorbidades associadas à COVID-19, como tabagismo, diabetes 15 Da mesma forma, foi observado maior número de comorbidades e média de idade superior em casos atendidos por instituições públicas e que evoluíram para óbito. Se é razoável supor a presença de maior número de comorbidades entre pessoas de maior média de idade, também é preciso questionar se, de fato, indivíduos provenientes da rede pública chegaram em estado mais grave, se a prevenção e controle das comorbidades nas instituições públicas é menos adequada. ...
Objetivo
Analisar os fatores associados ao óbito em indivíduos internados por COVID-19 em hospitais do Espírito Santo, Brasil.
Métodos
Estudo transversal, com dados secundários. Modelos de regressão logística foram empregados para estimar razões de chance (odds ratio: OR) brutas e ajustadas.
Resultados
Até 14 de maio de 2020, 200 indivíduos receberam alta e 220 foram a óbito. Do total de pessoas estudadas, 57,1% eram do sexo masculino, 46,4% maiores de 60 anos de idade, 57,9% foram notificados por instituição privada e 61,7% apresentaram mais de 1 comorbidade. Na análise ajustada, a mortalidade hospitalar foi maior entre aqueles nas faixas etárias de 51 a 60 (OR=4,33 – IC95% 1,50;12,46) e mais de 60 anos (OR=11,84 – IC95% 4,31;32,54), notificados por instituição pública (OR=8,23 – IC95% 4,84;13,99) e com maior número de comorbidades (duas [OR=2,74 – IC95% 1,40;5,34] e três [OR=2,90 – IC95% 1,07;7,81]).
Conclusão
Observa-se maior mortalidade em idosos, com comorbidades e usuários de hospitais públicos.
... Although haemoglobin was associated with VTE in the bivariate analysis, differences between patients who later had a thrombotic event and those who did not were not large. Advanced disease is considered a risk factor for VTE in lung cancer [17], and active smoking has also been associated with VTE risk [18]. Elevated FVIII (%) and D-dimer levels may reflect a hypercoagulable state, and sP-selectin may reflect endothelial and platelet expression of P-selectin, which is in the intersection between the coagulant and inflammatory pathways [19,20]. ...
Introduction:
Venous thromboembolism (VTE) is common in non-small cell lung cancer (NSCLC) patients undergoing systemic chemotherapy. The usefulness of Khorana score (KRS) to predict risk in lung cancer patients is limited, and the identification of patients who would benefit most from thromboprophylaxis is challenging. We aimed to identify variables whose values before chemotherapy helped in predicting VTE occurrence, and build a model to assess VTE risk.
Materials and methods:
A cohort of newly diagnosed NSCLC patients to undergo outpatient chemotherapy, not under anticoagulant treatment, was recruited. Pre-chemotherapy demographic, clinical, analytical and tumor-specific variables were collected. Patients were prospectively followed-up for 12 months to record VTE events. Bivariate and multivariate analyses were performed to identify VTE-associated variables, and a prediction model was built and compared with KRS.
Results:
90 patients were recruited, 18 of whom had a VTE event during follow-up. High baseline levels of factor VIII (FVIII) and, especially, soluble P-selectin (sP-selectin), were independently associated with VTE risk (hazard ratio [HR] 4.15, 95% confidence interval [CI] 1.17-14.71, and 66.40 [8.70-506.69], respectively). Our so-called Thrombo-NSCLC risk score, which assigns 1 and 3 points to high FVIII and sP-selectin values, respectively, was significantly better than KRS in predicting VTE (area under the curve [AUC] 0.93 vs. 0.55, sensitivity 94.4 vs. 35.0%, specificity 93.1 vs. 60.0%). Our prediction model showed significant discriminating capacity between high risk vs. intermediate/low risk patients, while KRS did not.
Conclusions:
The Thrombo-NSCLC risk score may be useful to identify those NSCLC patients who would benefit most from thromboprophylaxis.
... We also assessed the following secondary outcomes: operative time (OR), length of hospital stay (LoS), emergency department (ED) visits within 30 days postoperative, 30-day readmission, 30-day intervention, 30-day reoperation, leak rate (defined as drain present > 30 days, organ space surgical site infection, leak-related 30-day readmission, or leakrelated 30-day reoperation or intervention), bleeding event (defined as bleed-related 30-day readmission, bleed-related 30-day reoperation, or transfusion required within 72 h postoperatively), and 30-day morbidity (including unplanned admission rate to Intensive Care Unit within 30 days, pulmonary embolism, space surgical site infections, progressive renal insufficiency, postoperative sepsis, unplanned intubation, postoperative urinary tract infections, vein thrombosis requiring therapy, acute renal failure, postoperative cardiac arrest requiring CPR, coma over 24 h, stroke or cerebrovascular accident, postoperative deep incisional surgical site infections, postoperative myocardial infarction, postoperative ventilation, intraoperative nerve injury, pneumonia, postoperative septic shock, unplanned intubation, Clostridium difficile infection, and wound disruption). In the literature, there are pieces of evidence of increased vein thrombosis formation and postoperative pneumonia in smokers versus non-smokers [10,11]. To re-assess the observations, we decided to investigate vein thrombosis requiring therapy, pulmonary embolism, and pneumonia as separate outcomes. ...
Background
The exact impact of smoking within the last 12 months on the safety outcome of sleeve gastrectomy and Roux-Y gastric bypass is not well known. The study aimed to assess the effects of smoking on 30-day surgical outcomes.Methods
Preoperative characteristics and outcomes from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program dataset 2015–2018 were selected for all patients who underwent primary sleeve gastrectomy or Roux-Y gastric bypass. 30-day postoperative outcomes were assessed. We used propensity score matching to control for potential confounding.ResultsIn laparoscopic sleeve gastrectomy group, 29 165 pairs were included in the analysis. Smoking increased risk for inpatients readmission rate (3.67% vs. 3.10%; RR, 1.18; 95%CI 1.08–1.29, p < 0.001), intervention rate (1.03% vs. 0.84%; RR, 1.22; 95%CI 1.00–1.24, p = 0.020), reoperation rate (0.99% vs. 0.79%; RR, 1.25; 95%CI 1.05–1.48, p = 0.010), and leak rate (0.59% vs. 0.32%; RR, 1.83; 95%CI 1.43–2.37, p < 0.001). In laparoscopic Roux-Y gastric bypass cohort,11 895 pairs were included in the ultimate analysis. Smoking increased risk for inpatients readmission rate (7.54% vs. 5.88%; RR, 1.28; 95%CI 1.16–1.41, p < 0.001), intervention rate (3.53% vs. 2.30%; RR, 1.54; 95%CI 1.32–1.80, p < 001), reoperation rate (3.17% vs. 1.86%; RR, 1.70; 95%CI 1.45–2.00, p < 0.001), leak rate (1.05% vs. 0.59%; RR, 1.78; 95%CI 1.33–2.39, p < 0.001), bleed rate (2.03% vs. 1.45%; RR, 1.39; 95%CI 1.15–1.69, p < 0.001), and morbidity (4.20% vs. 3.38%; RR, 1.24; 95%CI 1.09–1.41, p = 0.001).Conclusion
Smoking cigarettes at any point within the 12 months before admission for surgery increased the risk for surgical short-term complications in bariatric patients. The effect was the most significant regarding leaks.
... The Tromsø study showed that heavy smokers (>20 pack-years) had an increased risk for total VTE (hazard ratio [HR] 1.46) and provoked VTE (HR 1.75) compared to never smokers. 31 Similarly, the Multiple Environmental and Genetic Assessment of risk factors for VTE (MEGA study) reported that overweight and obese individuals were associated with a 1.7-and 2.4-fold increase in VTE, respectively, compared to individuals of healthy weight. 32 Many of the patients included in this review presented with risk factors identified in these studies. ...
Background: Thrombosis, well known as a condition of the elderly, is occurring in the otherwise healthy adolescent population. Immobility is a significant risk factor for venous thromboembolism (VTE), and adolescents who play video games are immobile for extended periods of time. Some are presenting with VTE. When other risk factors such as obesity are present, the risk of VTE formation increases. We provide a review of published case reports regarding gaming and thrombosis.
Methods: We searched PubMed, Scopus, Web of Science, and EBSCO for articles published through July 2019, using the keywords “computer game thrombosis,” “computer game pulmonary embolism,” “computer game deep vein thrombosis,” “video game thrombosis,” “video game pulmonary embolism,” and “video game deep vein thrombosis.”
Results: Of the 26 articles we identified, we included 12 articles in our review that report a total of 15 cases, of which 2 resulted in fatalities. Modifiable risk factors included cigarette use, being overweight, birth control use, and prolonged immobility. Anticoagulation was the principal treatment modality in patients presenting with gaming thrombosis.
Conclusion: We strongly encourage screening gamers for possible VTEs if clinically warranted.
... 2,3 These malignancies of the upper GI tract share common lifestyle risk factors such as tobacco smoking, alcohol, and obesity, which are also associated with the development of venous thrombosis. [4][5][6] There exists significant discordance in the published literature regarding the incidence, risks, and timing of VTE events in patients undergoing surgery for esophageal or gastric cancer. 3,7 Additionally, for each of esophageal and gastric cancer surgery, it has not been shown if variation in risk exists between different age groups, comorbidity, and gender. ...
To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32–219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44–267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49–15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.
... 23,42 In children, PE is usually associated with DVT and is rarely unprovoked. Serious chronic medical conditions and central venous lines are considered likely triggers of PE. 43 VTE may be viewed as part of the cardiovascular disease continuum, and common risk factors-such as cigarette smoking, obesity, hypercholesterolaemia, hypertension, and diabetes 52,53 Myocardial infarction and heart failure increase the risk of PE. 54,55 Conversely, patients with VTE have an increased risk of subsequent myocardial infarction and stroke, or peripheral arterial embolization. 56 ...
... VTE may be viewed as part of the cardiovascular disease continuum, and common risk factors-such as cigarette smoking, obesity, hypercholesterolaemia, hypertension, and diabetes mellitus [44][45][46][47]-are shared with arterial disease, notably atherosclerosis [48][49][50][51]. However, this may be an indirect association mediated, at least in part, by the complications of coronary artery disease and, in the case of smoking, cancer [52,53]. Myocardial infarction and heart failure increase the risk of PE [54,55]. ...
Background Given the current debate in clinical research about the relationship between tobacco smoking and the risk of venous thromboembolism (VTE), a Mendelian randomization (MR) study was conducted aimed at elucidating the causal associations of current and past tobacco smoking with the risk of VTE, from the perspective of genetics.
Methods Two-sample univariate and multivariable MR analyses were designed, using summary-level data from large genome-wide association studies involving European individuals. Causality was primarily assessed using multiplicative fixed-effects or random-effects model and inverse variance weighting, supplemented by MR–Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out for sensitivity analysis to test the reliability of the results.
Results In the univariate MR analysis, no significant causal effects were found between current tobacco smoking and the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE). Similarly, no significant causal effects were found between past smoking and VTE, DVT, and PE. As for the multivariable MR analysis, results were consistent with univariate MR analysis, with no significant causal effect of either current or past tobacco smoking on the risk of VTE, DVT, and PE.
Conclusion Evidence from both univariate and multivariable MR analyses demonstrated no significant causal relationships between current and past tobacco smoking and VTE, DVT, and PE. This contradicts positive correlations reported in some previous observational studies, which may be explained by other confounding factors. This provided genetic evidence for the conclusion reported in other observational studies that smoking did not affect VTE risk.
Objective
Pulmonary embolisms (PE) are clinically challenging because of their high morbidity and mortality. This study aimed to create a nomogram to accurately predict the risk of PE in respiratory department patients in order to enhance their medical treatment and management.
Methods
This study utilized a retrospective method to collect information on medical history, complications, specific clinical characteristics, and laboratory biomarker results of suspected PE patients who were admitted to the respiratory department at Affiliated Dongyang Hospital of Wenzhou Medical University between January 2012 and December 2021. This study involved a total of 3,511 patients who were randomly divided into a training group (six parts) and a validation group (four parts) based on a 6:4 ratio. The LASSO regression and multivariate logistic regression were used to develop a scoring model using a nomogram. The performance of the model was evaluated using receiver operating characteristic curve (AUC), calibration curve, and clinical decision curve.
Results
Our research included more than 50 features from 3,511 patients. The nomogram-based scoring model was established using six predictive features including age, smoke, temperature, systolic pressure, D-dimer, and fibrinogen, which achieved AUC values of 0.746 in the training cohort (95% CI 0.720–0.765) and 0.724 in the validation cohort (95% CI 0.695–0.753). The results of the calibration curve revealed a strong consistency between probability predicted by the nomogram and actual probability. The decision curve analysis (DCA) also demonstrated that the nomogram-based scoring model produced a favorable net clinical benefit.
Conclusion
In this study, we successfully developed a novel numerical model that can predict the risk of PE in respiratory department patients suspected of PE, which can not only appropriately select PE prevention strategies but also decrease unnecessary computed tomographic pulmonary angiography (CTPA) scans and their adverse effects.
Background
Whether sex‐specific differences exist for risk factors for pulmonary embolism (PE) and deep venous thrombosis (DVT), with the exception of pregnancy and estrogen therapy, has been sparsely studied. We aimed to study whether sex‐specific differences of risk factors exist for noncancer‐related DVT and PE in middle‐aged and older individuals without cardiovascular history or previous diagnosis in a population‐based historical (retrospective) cohort.
Methods and Results
Potential venous thromboembolism (VTE) risk factors were registered at baseline in 15 807 women and 9996 men aged 44 to 74 years, who participated in the Malmö Diet and Cancer study (1991–1996). We excluded subjects with a previous history of VTE, cancer, a diagnosis of cardiovascular disease, or a diagnosis of cancer‐associated VTE during follow‐up. Patients were followed up from baseline until the first event of PE or DVT, death, or December 31, 2018. During the follow‐up period, 365 (2.3%) women and 168 (1.7%) men were affected by first DVT, and 309 (2.0%) women and 154 (1.5%) men were affected by first PE. In the multivariable Cox regression models, the anthropometric obesity markers of weight, body mass index, waist and hip circumference, fat percentage, and muscle weight were in a dose‐dependent way associated with DVT and PE among women but not men. In an analysis that included patients with cardiovascular disease and cancer‐related VTE, the results were similar for women. For men, several obesity measures became significantly associated with PE or DVT but were weaker than in women, especially for DVT.
Conclusions
Anthropometric obesity measures are more important risk factors for both DVT and PE among women than men, especially for individuals without cardiovascular history or previous diagnosis or cancer‐related VTE.
Venous thromboembolism (VTE) is a frequent disease affecting more than 1 in 12 individuals during their lifetime. VTE is associated with a substantial disease burden due to long-term complications such as recurrence, the post-thrombotic syndrome, and the post-pulmonary embolism syndrome. Despite the knowledge of several risk factors and triggers, more than one third of the VTE events occur in the absence of an obvious provoking factor. In this narrative review, we summarize studies presenting time trends in incidence rates of VTE after year 2000 and discuss potential reasons for the incidence trends as well as challenges for VTE prevention at the population level. Studies from US, Europe and Asia indicate that the incidence rates of VTE have increased slightly during the last twenty years. Of note, this increase has persisted beyond the implementation of computed tomography pulmonary angiography (CTPA) into routine clinical practice. The persisting rates are likely attributed to the concomitant increase in major risk factors for VTE, such as obesity, major surgery, and cancer. Apparently, more widespread use of thromboprophylaxis to high-risk groups have not counteracted the rates noticeably, indicating that an approach to change the risk factor profile in the general population may be warranted. Obesity is recognized as the strongest causal lifestyle factor for VTE with a population attributable fraction of 10–30%. However, the mechanisms by which obesity increases the VTE risk are poorly understood. By integrating multi-omics and system biology approaches, future epidemiological studies should focus on identifying biological pathways that drive thrombogenesis to reveal disease mechanisms and potential targets for prevention.
Introduction
The collected evidence on thrombophilia guidelines is scarce and data about their impact on clinical decisions are unknown. We aimed to investigate the adherence to thrombophilia testing guidelines, its therapeutic impact in patients with guideline-adherent and non-adherent testing and identify the patients' clinical characteristics mostly associated with treatment decisions.
Materials and methods
We conducted a single-center cross-sectional study of patients referred for thrombophilia testing at the outpatient clinic of a tertiary hospital between 01/2010–10/2020. We systematically evaluated the adherence of thrombophilia testing to internal guidelines and the influence of test results on anticoagulation therapy. Using multivariable logistic regression, we evaluated the association between clinical characteristics and influence of thrombophilia tests on anticoagulation therapy in the entire cohort and by indication for referral.
Results
Of 3686 included patients, mostly referred for venous thromboembolism (2407, 65 %) or arterial thrombosis (591, 16 %), 3550 patients (96 %) underwent thrombophilia testing. Indication for testing was according to guidelines in 1208 patients (33 %). Test results influenced treatment decisions in 56 of 1102 work-ups (5.1 %) that were adherent to guidelines, and in 237 of 2448 (9.7 %) non-adherent work-ups (absolute difference, 4.3 %; 95 % confidence interval, 2.9–6.3 %). Age < 50 years, female sex, absence of risk factors and co-morbidities, weakly provoked venous thromboembolism and referral indication other than venous thromboembolism were associated with influence on anticoagulation therapy.
Conclusions
Adherence to guidelines for thrombophilia testing was poor and did not have an impact on treatment decisions. Refinement of selection criteria is needed to increase the therapeutic impact of thrombophilia testing.
Background
Several studies agree that high socioeconomic position is protective against risk of PE. However, socioeconomic impact on outcomes from PE is not known. In this paper we aimed to compare differences in risk of recurrence and mortality within the first year following a first-time PE across level of education.
Methods
Using Danish national registers, patients ≥18 years of age hospitalized with a first-time PE between 1998 and 2018 were registered. Based on International Standard Classification of Education system 2011 patients were divided into four levels of education. Risk of recurrence and death across educational level were assessed by cumulative incidence curves and multivariable adjusted absolute risk regression analyses.
Results
In total, 22,708 patients with basic education (60 % women, median age 73 years), 19,809 with high school/vocational education (43 % women, median age 67 years), 7257 with short/medium higher education (54 % women, median age 65 years) and 2410 with long higher education (34 % women, median age 64 years) were hospitalized for PE. Risk of recurrence was not influenced by increasing educational level (relative absolute risk (RAR) 0.97, [95 % confidence interval (CI), 0.85–1.11], RAR 1.01 [95 % CI, 0.85–1.19], RAR 0.81 [95 % CI, 0.60–1.09]) compared to basic education, however, risk of death decreased with increasing level of education (RAR 0.93 [95 % CI, 0.90–0.96], RAR 0.88 [95 % CI, 0.83–0.92], RAR 0.83 [95 % CI, 0.76–0.89]).
Conclusion
Significant educational differences exist in mortality following PE, warranting a need for socially differentiated efforts targeted towards patients with low educational status.
Background
There are limited data on venous thromboembolism (VTE) incidence and predictive factors in non-small cell lung cancer (NSCLC) across first-line therapies.
Objective
To evaluate VTE incidence rates and identify predictive factors in NSCLC patients receiving first-line systemic therapies, including immune checkpoint inhibitors (ICIs).
Patients/methods
This is a single institution retrospective study of adult NSCLC patients who received first-line treatment, including chemotherapy, ICIs (pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab), and/or targeted therapies (TTs) (erlotinib, gefitinib, afatinib, osimertinib, crizotinib, alectinib, ceritinib). Risk factors included Khorana score, cancer stage, central venous catheter, pacemaker, comorbidities, and prior VTE. The primary objective - cumulative incidence of VTE at 6- and 12-months by treatment group – was compared using Gray's test. Univariable and multivariable competing risk analyses were used to identify predictors.
Results
Of 1587 evaluable patients, 53% were male, 79% white, 18% black, median age was 66; 58% had adenocarcinoma, 32% squamous cell carcinoma, and 47% metastatic disease; 1043 received chemotherapy, 171 ICIs, 157 chemotherapy plus concomitant ICI, 107 chemotherapy and durvalumab maintenance, and 109 TTs. The 6-month cumulative incidence of VTE by treatment type was 5.0%, 7.6%, 9.9%, 9.4%, and 11.1%; 12-month incidence was 6.5%, 9.0%, 12.8%, 12.2%, and 13.1% per arm, respectively (p = 0.01). Treatment type (p = 0.034) and nicotine dependence (p = 0.048) were significantly associated with time to VTE in multivariable analyses.
Conclusion
Treatment type and smoking status were predictive of time to VTE in NSCLC patients receiving various first-line therapies. Cumulative incidence was highest in those receiving TTs and combination chemotherapy plus ICI.
Background:
Surgery, which is a major risk factor for venous thrombosis, has rarely been considered a risk factor for arterial thrombosis. Recent studies have suggested that venous and arterial thromboses share common risk factors and have a bidirectional relationship. Accordingly, there is a growing interest in the risk of arterial thrombosis after surgery. We report a case of acute bilateral lower extremity arterial thromboses that developed after a prolonged surgery.
Case summary:
A 59-year-old man was hospitalized for intraocular foreign body removal surgery. He was a heavy-drinking smoker and had untreated hypertension and varicose veins in both legs. The operation was unexpectedly prolonged, lasting 4 h and 45 min. Immediately after emergence from general anesthesia, the patient complained of extreme pain in both legs. After the surgical drape was removed, cyanosis was evident in both feet of the patient. The pulse was not palpable, and continuous-wave Doppler signals were inaudible in the bilateral dorsalis pedis and posterior tibial arteries. Computed tomography angiography confirmed acute bilateral thrombotic occlusion of the popliteal arteries, proximal anterior tibial arteries, and tibioperoneal trunks. Arterial pulse returned in both lower limbs after 6 h of heparin initiation. The patient was discharged on postoperative day 26 without any sequelae.
Conclusion:
Acute lower extremity arterial thrombosis can occur after surgery. Anesthesiologists should pay particular attention to patients with risk factors for thrombosis.
Our aim was to evaluate the risk of venous thromboembolism (VTE) with tamoxifen and aromatase inhibitor in older women with breast cancer in the United States. The SEER-Medicare-linked database (2007--2013) was used for women of at least 65 years of age diagnosed with breast cancer in the United States. Logistic regression was used to examine unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CIs) for the risk of VTE. There were 178 059 women aged at least 65 years with breast cancer in the United States. Twenty-two thousand and forty-two (12.4%) women received tamoxifen, 64 384 (36.2%) women received aromatase inhibitors and 17 419 (9.8%) women received chemotherapy. Adjusted OR = 1.18 (95% CI 1.05--1.32) for VTE with tamoxifen for 3 years or less compared with tamoxifen use more than 3 years and OR = 1.07 (95% CI 1.05--1.16) for VTE with aromatase inhibitors 4 years or less compared with aromatase inhibitors use for more than 4 years. White women had OR = 1.19 (95% CI 1.05--1.35) and black women had OR = 1.07 (95% CI 0.76--1.51) for VTE with 3 years or less tamoxifen use compared with longer use. White women had OR = 1.09 (95% CI 1.00--1.18) and black women had OR = 1.07 (95% CI 0.86--1.34) for VTE with 4 years or less aromatase inhibitors use compared with longer use. Chemotherapy was associated with an increased risk of VTE (OR = 1.77, 95% CI 1.69--1.86). Chemotherapy combined with tamoxifen had OR = 1.64 (95% CI 1.45--1.86) and chemotherapy combined with aromatase inhibitors had OR = 1.71 95% CI 1.59-1.84). The study may help to identify a treatment profile for VTE risk that may facilitate VTE prevention.
Much of the focus in the venous thromboembolism (VTE) literature focuses on the care of the hospitalized acute pulmonary embolism (PE) patient. However, the care after hospital discharge is critical. In the post-PE outpatient setting, a number of decisions remain. These involve assessment of symptoms, anticoagulation risk/benefit and dosing, thrombophilia testing, decisions regarding surveillance for recurrent VTE, and ultimately monitoring for chronic thromboembolic disease. Very useful guidelines exist for the acutely ill PE patient but published guidelines and specific protocols for many aspects of post-PE care are lacking. We hope that we can offer a framework for post-discharge PE care by which the outpatient provider can provide a logical approach using the latest available evidence. We believe that the increasing research and published data in the realm of post-PE care mandates the involvement of VTE experts in the regular or at least periodic care of post-PE patients.
The incidence of venous thromboembolism is increasing in children, and along with neonates, the adolescent age group is among the most dramatically affected. Adolescent females are at particularly increased risk due to potential exposure to estrogen through pregnancy or hormonal supplementation for various reasons, as well as the predilection for some systemic inflammatory diseases to arise during this stage. Additionally, substance abuse and mental health disorders, conditions also associated with increased thrombosis risk, may be present at this time. This chapter explores venous thromboembolism prevalence, patient characteristics, and risk factors in this population.
Objectives:
Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age.
Results:
A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ± 15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others.
Conclusion:
This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.
Venous thromboembolism (VTE) is generally considered a process very different from arterial atherosclerosis. The role of tobacco is well known in arterial thrombosis. However, its role in VTE is less obvious and remains controversial. In this mini review, we analysed the literature to identify the role of active or passive smoking in perioperative VTE and the relationship between arterial atherosclerosis and VTE. We carried an Internet search in French and English including the following keywords: deep vein thrombosis, tobacco, cigarette smoking, pulmonary embolism, postoperative, postoperative, atherosclerosis. Regarding the relationship between tobacco and VTE, a total of 9 studies were identified. Studies were ranked by the risk of VTE in relation to active or passive smoking. In conclusion, the management of smoking during the perioperative period for a short-term arrest (minimum 4-8 weeks before the intervention), or long term, allows among others a reduction of arterial or venous thrombotic events. However, it is clear that the training of anaesthesiologists in the management of smoking will contribute to the reduction of this public health problem.
Background: There has been little interest in the association between floor level and cardiovascular disease (CVD). The only previous study that has been found, observed a negative association. Suggested explanations were: the vertical distribution of air pollution and environmental noise; use of stairs; and selection of individuals of different socioeconomic status to different floor levels. A positive association has also been suggested, with basis in theory about the atmosphere’s electric properties. The public health relevance of increasing the knowledge is given by globally increasing urbanization and growth in high-rise residencies. The aim of this study has been to investigate the association between residence floor level and prevalence of CVD, with emphasis on stroke.
Methods: We used cross-sectional data from the Health and Environment in Oslo study (HELMILO) conducted in 2009, with a representative sample (N=12.479) of the inhabitants of Oslo, Norway, aged 39-85 years. Three self-reported health outcomes representing prevalence were included: stroke, venous thromboembolism (VTE) and intermittent claudication (IC). We studied bivariate associations between floor of bedroom (0-1,2-3,4-5,6-10 and ≥11) and health outcomes with chi square tests. Potential confounders (measures of socio-demography, socioeconomic status (SES) (education and occupational status) and health behaviors) were controlled for in multivariate logistic regression methods. We also fitted separate models for block apartment residents, tested for the presence of linear trends, and whether time at address (1-10 years versus >10 years) modified any of the associations.
Result: The prevalence of all health outcomes differed across floor levels (p<0.01 in all instances). In adjusted analyses, residents of 6-10th floor had an increased odds of VTE history (OR 1.720; 95 % CI 1.174-2.518) and residents of 11th floor or higher had an increased odds of IC history (OR 2.318; 95 % CI 1.237-4.345), compared to basement and 1st floor. We also found significant trends of increasing disease prevalence by floor level for all outcomes, including stroke. The associations disappeared upon investigations of block apartment residents separately, except for a higher odds of VTE history in residents of 6th floor or higher (OR 1.504; 95 % CI 1.007-2.247). Time at address did not modify any associations.
Conclusion: Floor level is positively associated with prevalence of CVD among inhabitants of Oslo. The disappearance of trends when we investigated block apartments separately may indicate residual confounding by building height and SES (income). The remaining association between floor level and VTE may point to an effect of floor level per se, although further residual confounding by income, building height and possibly psychosocial factors seems more plausible. The findings can hardly be taken in support of any of the earlier proposed mechanisms for an association between floor level and CVD, and indicate a need for more studies.
Abstract
Venous thromboembolism (VTE) is generally considered a process very different from arterial atherosclerosis. The role of tobacco is well known in arterial thrombosis. However, its role in VTE is less obvious and remains controversial. In this mini review, we analysed the literature to identify the role of active or passive smoking in perioperative VTE and the relationship between arterial atherosclerosis and VTE. We carried an Internet search in French and English including the following keywords: deep vein thrombosis, tobacco, cigarette smoking, pulmonary embolism, postoperative, postoperative, atherosclerosis. Regarding the relationship between tobacco and VTE, a total of 9 studies were identified. Studies were ranked by the risk of VTE in relation to active or passive smoking. In conclusion, the management of smoking during the perioperative period for a short-term arrest (minimum 4–8 weeks before the intervention), or long term, allows among others a reduction of arterial or venous thrombotic events. However, it is clear that the training of anaesthesiologists in the management of smoking will contribute to the reduction of this public health problem.
Apart from obesity, it remains controversial whether atherosclerosis and its cardiovascular risk disease (CVD) factors are associated with risk of venous thromboembolism (VTE). Using data from the Atherosclerosis Risk in Communities study (ARIC), we evaluated associations between CVD risk factors and incident VTE in a cohort of 15,340 participants who were free a history of VTE and/or anticoagulant use on enrolment. The CVD risk factors were updated during the follow-up period. Over a mean follow-up time of 15.5 years (237,375 person-years), 468 participants had VTE events. Adjusting for demographic variables and body mass index (BMI), current smokers were at greater risk [HR of 1.44 (95% CI: 1.12-1.86)] compared to non-smokers. There was a positive monotonic association between BMI and VTE risk. Individuals with a BMI ≥35 kg/m² had a HR for VTE of 3.09 (95%CI: 2.26-4.23) compared to those with normal BMI (<25 kg/m²). Greater physical activity was associated with lower VTE risk in a demographic adjusted model; however, this association became non-significant following adjustment for BMI. Alcohol intake, diabetes, hypertension, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were not associated with VTE risk. In conclusion, among the well-established CVD risk factors, only current smoking and obesity were independently associated with VTE risk in this large cohort where risk factors were updated serially during follow-up. This finding corroborates that the pathogenesis of venous disease differs from that of atherosclerotic disease.
Venous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice.
We sought to document incidence, case-fatality, and recurrence rates of venous thromboembolism (VTE) in women and to explore the relationship of demographic, lifestyle, and anthropometric factors to VTE incidence.
Data from participants aged 55 to 69 years in the Iowa Women's Health Study were linked to Medicare data for 1986 through 2004 (n = 40 377) to identify hospitalized VTE patients.
A total of 2137 women developed VTE, yielding an incidence rate of 4.04 per 1000 person-years. The 28-day case-fatality rate was 7.7%, and the 1-year recurrence rate was 3.4%. Educational attainment, physical activity, and age at menopause were inversely associated with VTE. Risk of secondary (particularly cancer-related) VTE was higher among smokers than among those who had never smoked. Body mass index, waist circumference, waist-to-hip ratio, height, and diabetes were positively associated with VTE risk. Hormone replacement therapy use was associated with increased risk of idiopathic VTE.
VTE is a significant source of morbidity and mortality in older women. Risk was elevated among women who were smokers, physically inactive, overweight, and diabetic, indicating that lifestyle contributes to VTE risk.
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In prospective studies, disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey. However, because of "regression dilution," this generally tends to underestimate the real associations of disease rates with the "usual" levels of such risk factors during some particular exposure period. The "regression dilution ratio" describes the ratio of the steepness of the uncorrected association to that of the real association. To assess the relevance of the usual value of a risk factor during particular exposure periods (e.g., first, second, and third decades) to disease risks, regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period (e.g., at 5, 15, and 25 years, respectively). This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol. The analyses were based on biennial remeasurements over 30 years for participants in the Framingham Study (Framingham, Massachusetts) and a 26-year resurvey for a sample of men in the Whitehall Study (London, England). They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third, the second decade by about one-half, and the third decade by about two-thirds. Hence, to correct appropriately for regression dilution, replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants.
Risk factors for deep vein thrombosis and pulmonary embolism are mostly derived from case-control studies of hospitalized patients, and there are few long-term population-based studies.
To study the long-term risk factors for deep vein thrombosis and pulmonary embolism among middle-aged men.
A prospective cohort study.
General community, "The Study of Men Born in 1913."
A random population sample of 855 men, all aged 50 years at baseline.
Eight-hundred fifty-five men participated in a screening examination in 1963 at the age of 50 years, and 792 of these men were reexamined in 1967 at the age of 54. All the men were followed up with periodic examinations until the age of 80. Objective methods were used to ascertain a diagnosis of deep vein thrombosis or pulmonary embolism.
Waist circumference (P=.004) and smoking (P = .02) predicted a venous thromboembolic event in multivariate survival analysis. Men in the highest decile of waist circumference (> or =100 cm) had an adjusted relative risk of 3.92 (95% confidence interval, 2.10-7.29; P<.001) compared with men with a waist circumference of less than 100 cm. For men who smoked 15 g of tobacco (15 cigarettes) a day or more, the adjusted relative risk was 2.82 (95% confidence interval, 1.30-6.13; P= .009) compared with nonsmokers.
Smoking and abdominal obesity were independent risk factors for venous thromboembolic events during follow-up. In addition to the prevention of smoking and obesity, a more aggressive strategy regarding the use of prophylactic agents among smokers and obese patients, in various risk situations, may be justified.
The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies.
To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998.
There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95% CI, 1.0-2.1]).
Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.
Tobacco use is the single most important preventable health risk in the developed world, and an important cause of premature death worldwide. Smoking causes a wide range of diseases, including many types of cancer, chronic obstructive pulmonary disease, coronary heart disease, stroke, peripheral vascular disease, and peptic ulcer disease. In addition, smoking during pregnancy adversely affects fetal and neonatal growth and development. Recent decades have seen a massive expansion in tobacco use in the developing world and accelerating growth in smoking among women in the developed world. Globally, smoking-related mortality is set to rise from 3 million annually (1995 estimate) to 10 million annually by 2030, with 70% of these deaths occurring in developing countries. Many of the adverse health effects of smoking are reversible, and smoking cessation treatments represent some of the most cost effective of all healthcare interventions. Although the greatest benefit accrues from ceasing smoking when young, even quitting in middle age avoids much of the excess healthcare risk associated with smoking. In order to improve smoking cessation rates, effective behavioural and pharmacological treatments, coupled with professional counselling and advice, are required. Since smoking duration is the principal risk factor for smoking-related morbidity, the treatment goal should be early cessation and prevention of relapse.
Epidemiological studies of the validity and reliability of self-reported information on important risk factors for non-communicable chronic diseases are scarce in Brazil.
We evaluated the test-retest reliability of information--overall and stratified by gender, age and education--on active and passive smoking, alcohol intake and aspects of dietary habits.
Test-retest reliability.
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
192 University employees.
Self-administered questionnaires were completed on two occasions, two weeks apart.
Kappa Statistics; Intraclass Correlation Coefficient.
Information on smoking status and pack-years smoked had almost perfect levels of agreement, respectively, kappa = 0.97 (95% CI, 0.92-1.00), and intraclass correlation coefficient = 0.93 (CI 95%, 0.89-0.96). Characteristics of alcohol intake yielded substantial levels of agreement (kappa ranging from 0.62 to 0.69). The reproducibility of the information on dietary habits varied from 0.67 to 0.79 (kappa). No clear-cut patterns could be identified comparing information by age or gender. There was a slight tendency towards greater reliability among people with higher levels of education.
The reproducibility of information on smoking, drinking, and dietary patterns ranged from substantial to excellent, as investigated in the Pró-Saúde Study, a longitudinal investigation recently launched in Rio de Janeiro.
Lung cancer remains a devastating disease associated with substantial morbidity and mortality. Recent research has suggested that lung cancer screening with spiral computed tomography scans might reduce lung cancer mortality. Studies of lung cancer screening have also suggested that significant numbers of participants quit smoking after screening. However, most have relied solely on self-reported smoking behavior, which may be less accurate among participants in lung cancer screening. To assess the validity of self-reported smoking status among participants in a lung cancer screening trial, this study compared self-reported smoking status against urinary cotinine levels. The sample included 55 consecutive participants enrolled in a randomized clinical trial comparing annual spiral computed tomography and chest X-ray for lung cancer screening. Participants were a mean of 59 years of age and predominantly Caucasian (96%) and male (55%). Self-reported smoking status was assessed before and after participants learned of the purpose of the biochemical verification study. Using urinary cotinine as the "gold standard," the sensitivity and specificity of self-reported smoking status were 91% and 95%, respectively (kappa = 0.85, P < 0.001, 95% confidence interval = 0.71-0.99). Total misclassification rate was 7%. However, three of the four misclassified participants reported concurrent use of nicotine replacement strategies. Eliminating these cases from the analysis revealed sensitivity of 100% and specificity of 95% (kappa = 0.96, P < 0.001, 95% confidence interval = 0.88-1.00). In conclusion, self-reported smoking status among participants in a lung cancer screening trial was highly consistent with urinary cotinine test results.
Background
Risk factors for deep vein thrombosis and pulmonary embolism are mostly derived from case-control studies of hospitalized patients, and there are few long-term population-based studies.
Objective
To study the long-term risk factors for deep vein thrombosis and pulmonary embolism among middle-aged men.
Design
A prospective cohort study.
Setting
General community, "The Study of Men Born in 1913."
Subjects
A random population sample of 855 men, all aged 50 years at baseline.
Main Outcome Measures
Eight-hundred fifty-five men participated in a screening examination in 1963 at the age of 50 years, and 792 of these men were reexamined in 1967 at the age of 54. All the men were followed up with periodic examinations until the age of 80. Objective methods were used to ascertain a diagnosis of deep vein thrombosis or pulmonary embolism.
Results
Waist circumference (P=.004) and smoking (P=.02) predicted a venous thromboembolic event in multivariate survival analysis. Men in the highest decile of waist circumference (≥100 cm) had an adjusted relative risk of 3.92 (95% confidence interval, 2.10-7.29; P<.001) compared with men with a waist circumference of less than 100 cm. For men who smoked 15 g of tobacco (15 cigarettes) a day or more, the adjusted relative risk was 2.82 (95% confidence interval, 1.30-6.13; P=.009) compared with nonsmokers.
Conclusions
Smoking and abdominal obesity were independent risk factors for venous thromboembolic events during follow-up. In addition to the prevention of smoking and obesity, a more aggressive strategy regarding the use of prophylactic agents among smokers and obese patients, in various risk situations, may be justified.
Objective.
—To investigate risk factors for pulmonary embolism in women.Design.
—Prospective study based on biennial, mailed questionnaires.Setting.
—Nurses' Health Study with 16 years of follow-up from 1976 to 1992.Patients.
—A group of 112 822 women aged 30 to 55 years in 1976, free from diagnosed cardiovascular disease or cancer at baseline. Overall, there were 1 619770 person-years of follow-up.Measurements.
—Based on self-report and medical records, we documented 280 cases of pulmonary embolism, of which 125 were primary (no identified antecedent cancer, trauma, surgery, or immobilization). Information on height, weight, cigarette smoking, hypertension, diabetes, and hypercholesterolemia was collected by questionnaire.Results.
—In multivariate analysis, obesity, cigarette smoking, and hypertension were independent predictors of pulmonary embolism. Specifically, obese women (body mass index ≥ 29.0 kg/m2) had an increased risk of primary pulmonary embolism (multivariate relative risk=2.9; 95% confidence interval [CI], 1.5-5.4). Heavy cigarette smokers also had an increased risk of primary pulmonary embolism. The relative risk (RR) of primary pulmonary embolism was 1.9 (95% CI, 0.9-3.7) for women currently smoking 25 to 34 cigarettes per day and 3.3 (95% CI, 1.7-6.5) for those smoking 35 cigarettes or more daily as compared with never smokers. Hypertension, even after adjustment for body mass index, was also associated with an increased risk of primary pulmonary embolism (RR=1.9; 95% CI, 1.2-2.8). High serum cholesterol levels (RR=1.1; 95% CI, 0.62-1.8) and diabetes (RR=0.7; 95% CI, 0.3-1.9) did not appear to be related to primary pulmonary embolism.Conclusion.
—These prospective data indicate that obesity, cigarette smoking, and hypertension are associated with increased risk of pulmonary embolism in women. Control of these risk factors will decrease risks of pulmonary embolism as well as coronary heart disease.
Tobacco use is the single most important preventable health risk in the developed world, and an important cause of premature death worldwide. Smoking causes a wide range of diseases, including many types of cancer, chronic obstructive pulmonary disease, coronary heart disease, stroke, peripheral vascular disease, and peptic ulcer disease. In addition, smoking during pregnancy adversely affects fetal and neonatal growth and development. Recent decades have seen a massive expansion in tobacco use in the developing world and accelerating growth in smoking among women in the developed world. Globally, smoking-related mortality is set to rise from 3 million annually (1995 estimate) to 10 million annually by 2030, with 70% of these deaths occurring in developing countries.
Many of the adverse health effects of smoking are reversible, and smoking cessation treatments represent some of the most cost effective of all healthcare interventions. Although the greatest benefit accrues from ceasing smoking when young, even quitting in middle age avoids much of the excess healthcare risk associated with smoking. In order to improve smoking cessation rates, effective behavioural and pharmacological treatments, coupled with professional counselling and advice, are required. Since smoking duration is the principal risk factor for smoking-related morbidity, the treatment goal should be early cessation and prevention of relapse.
Summary Background In some studies, venous thromboembolism has been associated with atherosclerosis and with the risk of arterial cardiovascular events such as myocardial infarction and stroke. Other studies, however, do not show this association. To help clarify these discrepant fi ndings, we aimed to investigate the risk of arterial cardiovascular events in patients who were diagnosed with venous thromboembolism. Methods We undertook a 20-year population-based cohort study using data from nationwide Danish medical databases. After excluding those with known cardiovascular disease, we assessed the risk of myocardial infarction and stroke in 25 199 patients with deep venous thrombosis, 16 925 patients with pulmonary embolism, and 163 566 population controls. Findings For patients with deep venous thrombosis, the relative risks varied from 1·60 for myocardial infarction (95% CI 1·35–1·91) to 2·19 (1·85–2·60) for stroke in the fi rst year after the thrombotic event. For patients with pulmonary embolism, the relative risks in that year were 2·60 (2·14–3·14) for myocardial infarction and 2·93 (2·34–3·66) for stroke. The relative risks were also raised, though less markedly, during the subsequent 20 years of follow-up, with 20–40% increases in risk for arterial cardiovascular events. Relative risks were similar for those with provoked and unprovoked deep venous thrombosis and pulmonary embolism.
Competing risks observations, in which patients are subject to a number of potential failure events, are a feature of most clinical cancer studies. With competing risks, several modeling approaches are available to evaluate the relationship of covariates to cause-specific failures. We discuss the use and interpretation of commonly used competing risks regression models.
For competing risks analysis, the influence of covariate can be evaluated in relation to cause-specific hazard or on the cumulative incidence of the failure types. We present simulation studies to illustrate how covariate effects differ between these approaches. We then show the implications of model choice in an example from a Radiation Therapy Oncology Group (RTOG) clinical trial for prostate cancer.
The simulation studies illustrate that, depending on the relationship of a covariate to both the failure type of principal interest and the competing failure type, different models can result in substantially different effects. For example, a covariate that has no direct influence on the hazard of a primary event can still be significantly associated with the cumulative probability of that event, if the covariate influences the hazard of a competing event. This is a logical consequence of a fundamental difference between the model formulations. The example from RTOG similarly shows differences in the influence of age and tumor grade depending on the endpoint and the model type used.
Competing risks regression modeling requires that one considers the specific question of interest and subsequent choice of the best model to address it.
Venous thromboembolism (VTE), defined as deep vein thrombosis, pulmonary embolism, or both, affects an estimated 300,000-600,000 individuals in the U.S. each year, causing considerable morbidity and mortality. It is a disorder that can occur in all races and ethnicities, all age groups, and both genders. With many of the known risk factors-advanced age, immobility, surgery, obesity-increasing in society, VTE is an important and growing public health problem. Recently, a marked increase has occurred in federal and national efforts to raise awareness and acknowledge the need for VTE prevention. Yet, many basic public health functions-surveillance, research, and awareness-are still needed. Learning and understanding more about the burden and causes of VTE, and raising awareness among the public and healthcare providers through a comprehensive public health approach, has enormous potential to prevent and reduce death and morbidity from deep vein thrombosis and pulmonary embolism throughout the U.S.
Osteoprotegerin (OPG) concentration in serum is associated with the presence and severity of atherosclerosis.
To investigate the association between serum osteoprotegerin and the risk of a future myocardial infarction, ischemic stroke and mortality in a general population.
OPG was measured in serum collected from 6265 subjects recruited from a general population without a prior myocardial infarction and ischemic stroke (the Tromsø Study). Incident myocardial infarction, ischemic stroke and mortality were registered during follow-up. Cox regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals (HR; 95% CI).
There were 575 myocardial infarctions, 284 ischemic strokes and 824 deaths (146 deaths as a result of ischemic heart disease, 78 deaths because of stroke and 600 deaths due to other causes) in the cohort during a median of 10.6 years of follow-up. Serum OPG (per SD [1.13 ng mL(-1)] increase in OPG) was associated with an increased risk of a myocardial infarction (1.20; 1.11-1.31), ischemic stroke (1.32; 1.18-1.47), total mortality (1.34; 1.26-1.42), death because of ischemic heart disease, (1.35; 1.18-1.54), stroke (1.44; 1.19-1.75) and non-vascular causes (1.31; 1.22-1.41) after adjustment for age, gender, current smoking, systolic blood pressure, body mass index, high density lipoprotein cholesterol, total cholesterol, creatinine, high sensitivity C-reactive protein (CRP) and diabetes mellitus or HbA1c > 6.1%. No association was detected between OPG and incident hemorrhagic stroke (1.02; 0.73-1.43).
Serum OPG was associated with future risk of myocardial infarction, ischemic stroke, total mortality, mortality of ischemic heart disease, stroke and of non-vascular causes independent of traditional cardiovascular risk factors.
Studies have suggested a link between risk factors for atherosclerotic disease and venous thromboembolism (VTE), but results are heterogeneous. We sought to identify risk factors for VTE with a focus on risk factors for atherosclerotic disease.
Data were taken from the Copenhagen City Heart Study, a prospective cohort study of a random, age-stratified sample of people living in a defined area in Copenhagen, Denmark, started in 1976 with follow-up until 2007. First VTE (deep vein thrombosis and pulmonary embolism) diagnosis was retrieved from electronic national registries from study baseline to 2007. Of 18 954 subjects (median follow-up, 19.5 years) representing 360 399 person-years of follow-up, 969 subjects experienced at least 1 VTE, corresponding to a crude incidence rate of 2.69 (95% confidence interval [CI], 2.52 to 2.86) per 1000 person-years. The variables found to be significantly associated with VTE in a multivariable model adjusted for age and calendar time were as follows: body mass index (hazard ratio [HR] for >or=35 versus <20=2.10 [95% CI, 1.39 to 3.16]); smoking (HR for >or=25 g tobacco per day versus never smoker=1.52 [95% CI, 1.15 to 2.01]); gender (HR for men versus women=1.24 [95% CI, 1.08 to 1.42]); household income (HR for medium versus low=0.82 [95% CI, 0.70 to 0.95]); and diastolic blood pressure (HR for >100 versus <80 mm Hg=1.34 [95% CI, 1.08 to 1.66]). Other cardiovascular risk factors including total/high-density lipoprotein/low-density lipoprotein cholesterol levels, triglyceride levels, and diabetes mellitus were not associated with VTE.
Obesity and smoking were both found to be important risk factors for VTE whereas total/high-density lipoprotein/low-density lipoprotein cholesterol levels, triglyceride levels, and diabetes mellitus were not.
Previous large epidemiological studies reporting on the association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases mainly focussed on prevalent diseases rather than on the incidence of newly diagnosed cardiovascular outcomes. We used the UK-based General Practice Research Database (GPRD) to assess the prevalence and incidence of cardiovascular diseases in COPD patients aged 40-79 between 1995 and 2005, and we randomly matched COPD-free comparison patients to COPD patients. In nested-case control analyses, we compared the risks of developing an incident diagnosis of cardiac arrhythmias, venous thromboembolism, myocardial infarction, or stroke between patients with and without COPD, stratifying the analyses by COPD-severity, using COPD-treatment as proxy for disease severity. We identified 35,772 patients with COPD and the same number of COPD-free patients. Most cardiovascular diseases were more prevalent among COPD patients than among the comparison group of COPD-free patients. The relative risk estimates of developing an incident diagnosis of cardiac arrhythmia (OR 1.19, 95% CI 0.98-1.43), deep vein thrombosis (OR 1.35, 95% CI 0.97-1.89), pulmonary embolism (OR 2.51, 95% CI 1.62-3.87), myocardial infarction (OR 1.40, 95% CI 1.13-1.73), or stroke (OR 1.13, 95% CI 0.92-1.38), tended to be increased for patients with COPD as compared to COPD-free controls. The findings of this large observational study provide further evidence that patients with COPD are at increased risk for most cardiovascular diseases.
It is generally accepted that socio-economic status (SES) influences dietary habits as well as human health. Three main parameters have been most often used to define SES, i.e., occupation, education and income. These characteristics cover different aspects of the socio-economic structure of people. The aim of this review is to present the current knowledge regarding the relationships between SES, dietary habits and health-related outcomes in various parts of the world.
Large-scale prospective studies are needed to assess whether smoking is associated with venous thromboembolism (VTE) (i.e. deep venous thrombosis and pulmonary embolism) independently of established risk factors.
To investigate the association between smoking and the risk of VTE among middle-aged men and women.
From 1993 to 1997, 27,178 men and 29,875 women, aged 50-64 years and born in Denmark, were recruited into the Danish prospective study 'Diet, Cancer and Health'. During follow-up, VTE cases were identified in the Danish National Patient Registry. Medical records were reviewed and only verified VTE cases were included in the study. Baseline data on smoking and potential confounders were included in gender stratified Cox proportional hazard models to asses the association between smoking and the risk of VTE. The analyses were adjusted for alcohol intake, body mass index, physical activity, and in women also for use of hormone replacement therapy.
During follow-up, 641 incident cases of VTE were verified. We found a positive association between current smoking and VTE, with a hazard ratio of 1.52 (95% CI, 1.15-2.00) for smoking women and 1.32 (95% CI, 1.00-1.74) for smoking men, and a positive dose-response relationship. Former smokers had the same hazard as never smokers.
Smoking was an independent risk factor for VTE among middle-aged men and women. Former smokers have the same risk of VTE as never smokers, indicating acute effects of smoking, and underscoring the potential benefits of smoking cessation.
There has been a great advance in our knowledge of the role that thrombophilic factors play in the risk of venous thromboembolic events (VTE). However, the effect of lifestyle factors on VTE has been inadequately explored in large scale studies of women. This cohort study comprised one thousand native Swedish women for each age year between 25 and 64 inclusive (total = 40,000) drawn from the South Swedish population registry for 1990 (n = 40,000), who were followed for a mean of eleven years. Seventy-four percent completed a questionnaire at the inception of the study (n = 29,518) and 24,098 women responded to a follow-up inquiry between the years 2000-2002. The main outcome was the relationship between VTE and physical exercise, smoking habits, and alcohol consumption. Moderate drinkers of alcohol (10-15 g/d) and women engaged in strenuous exercise were at half the risk of VTE compared to those who consumed little or no alcohol or lived a sedentary life. Heavy smoking was associated with a 30% increased risk of VTE. Lifestyle factors have a major impact on the risk of VTE. Women non-smokers who were physically active and who consumed alcohol in moderation were at a lower risk of VTE.
Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI.
The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population-based study.
Traditional cardiovascular risk factors and family history of MI were registered in 21,330 subjects, aged 25-96 years, enrolled in the Tromsø study in 1994-95. First-lifetime VTE events during follow-up were registered up to 1 September 2007.
There were 327 VTE events (1.40 per 1000 person-years), 138 (42%) unprovoked, during a mean of 10.9 years of follow-up. In age- and gender-adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82-2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01-1.55), body mass index (BMI; HR per 3 kg m(-2), 1.21; 95% CI, 1.13-1.31), and family history of MI (HR, 1.31; 95% CI, 1.04-1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01-1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03-2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL-cholesterol, triglycerides, and smoking were not independently associated with total VTE.
Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.
To assess potential long-term risk factors for major pulmonary embolism, 46 subjects from the Framingham Heart Study with autopsy-confirmed and clinically significant pulmonary embolism were identified in whom age, systolic blood pressure, cholesterol level, cigarette use, glucose level, Metropolitan relative weight, and varicose veins were ascertained at entry into the Study. These variables were compared among these 46 subjects, all 3,470 subjects in whom these variables were measured at the inception of the Study, and the 998 of these subjects who died within 26 years of follow-up. In multivariate analysis of subjects with autopsy-confirmed major pulmonary embolism and all subjects who died, only Metropolitan relative weight was significantly and independently associated with pulmonary embolism and only among women (p less than 0.001). These findings indicate that, in this cohort, increased adiposity in women is an important long-term factor for significant pulmonary embolism at autopsy. This raises the possibility that weight reduction in obese women may decrease the chances of pulmonary embolism.
To investigate risk factors for pulmonary embolism in women.
Prospective study based on biennial, mailed questionnaires.
Nurses' Health Study with 16 years of follow-up from 1976 to 1992.
A group of 112822 women aged 30 to 55 years in 1976, free from diagnosed cardiovascular disease or cancer at baseline. Overall, there were 1619770 person-years of follow-up.
Based on self-report and medical records, we documented 280 cases of pulmonary embolism, of which 125 were primary (no identified antecedent cancer, trauma, surgery, or immobilization). Information on height, weight, cigarette smoking, hypertension, diabetes, and hypercholesterolemia was collected by questionnaire.
In multivariate analysis, obesity, cigarette smoking, and hypertension were independent predictors of pulmonary embolism. Specifically, obese women (body mass index > or = 29.0 kg/m2) had an increased risk of primary pulmonary embolism (multivariate relative risk=2.9; 95% confidence interval [CI], 1.5-5.4). Heavy cigarette smokers also had an increased risk of primary pulmonary embolism. The relative risk (RR) of primary pulmonary embolism was 1.9 (95% CI, 0.9-3.7) for women currently smoking 25 to 34 cigarettes per day and 3.3 (95% CI, 1.7-6.5) for those smoking 35 cigarettes or more daily as compared with never smokers. Hypertension, even after adjustment for body mass index, was also associated with an increased risk of primary pulmonary embolism (RR=1.9; 95% CI, 1.2-2.8). High serum cholesterol levels (RR=1.1; 95% CI, 0.62-1.8) and diabetes (RR=0.7; 95% CI, 0.3-1.9) did not appear to be related to primary pulmonary embolism.
These prospective data indicate that obesity, cigarette smoking, and hypertension are associated with increased risk of pulmonary embolism in women. Control of these risk factors will decrease risks of pulmonary embolism as well as coronary heart disease.
The risk factors for venous thrombosis differ from those for arterial vascular disease. During the past 5 years, knowledge about the aetiology of venous thrombosis has advanced with the discovery of several factors that contribute to the incidence of thrombosis, particularly the role of coagulation abnormalities. These abnormalities are common in the general population and therefore will be present simultaneously in some individuals. The resultant gene-gene and gene-environment interactions between risk factors are the key to the understanding of why a certain person develops thrombosis at a specific point in time.
Venous thromboembolism (VTE) occurs for the first time in approximately 100 persons per 100,000 each year in the United States, and rises exponentially from <5 cases per 100,000 persons <15 years old to approximately 500 cases (0.5%) per 100,000 persons at age 80 years. Approximately one third of patients with symptomatic VTE manifest pulmonary embolism (PE), whereas two thirds manifest deep vein thrombosis (DVT) alone. Despite anticoagulant therapy, VTE recurs frequently in the first few months after the initial event, with a recurrence rate of approximately 7% at 6 months. Death occurs in approximately 6% of DVT cases and 12% of PE cases within 1 month of diagnosis. The time of year may affect the occurrence of VTE, with a higher incidence in the winter than in the summer. One major risk factor for VTE is ethnicity, with a significantly higher incidence among Caucasians and African Americans than among Hispanic persons and Asian-Pacific Islanders. Overall, approximately 25% to 50% of patient with first-time VTE have an idiopathic condition, without a readily identifiable risk factor. Early mortality after VTE is strongly associated with presentation as PE, advanced age, cancer, and underlying cardiovascular disease.
To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States.
The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review.
The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48% (175/366) of events. The 28-day case-fatality rate was 11% (29/265) after a first venous thromboembolism and 25% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7% per year (95% confidence interval [CI]: 4.5% to 10.9% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95% CI: 2.0 to 41.7).
The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.
The epidemiology of venous thromboembolism (VTE) in the community has important implications for VTE prevention and management. This review describes the disease burden (incidence), outcomes (survival, recurrence and complications) and risk factors for deep vein thrombosis and pulmonary embolism occurring in the community. Recent comprehensive studies of the epidemiology of VTE that reported the racial demography and included the full spectrum of disease occurring within a well-defined geographic area over time, separated by event type, incident vs. recurrent event and level of diagnostic certainty, were reviewed. Studies of VTE outcomes had to include a relevant duration of follow-up. VTE incidence among whites of European origin exceeded 1 per 1000; the incidence among persons of African and Asian origin may be higher and lower, respectively. VTE incidence over recent time remains unchanged. Survival after VTE is worse than expected, especially for pulmonary embolism. Thirty percent of patients develop VTE recurrence and venous stasis syndrome. Exposures can identify populations at risk but have a low predictive value for the individual. An acquired or familial thrombophilia may predict the subset of exposed persons who actually develop symptomatic VTE. In conclusion, VTE is a common, lethal disease that recurs frequently and causes serious long-term complications. To improve survival and prevent complications, VTE occurrence must be reduced. Better individual risk stratification is needed in order to modify exposures and target primary and secondary prophylaxis to the person who would benefit most.
Methods for formal comparison of competing risks may clarify uncertainties about the associations of atherosclerotic risk
factors with the development of venous thromboembolism (VTE). For a median of 20.1 years, the Physicians' Health Study (1982–2003)
followed 18,662 US male physicians with no prior myocardial infarction, stroke, VTE, or cancer and for whom reported risk
factor information was available at baseline. The authors used methods of competing risk survival analysis to compare relative
hazard rates associated with age, hypertension, elevated cholesterol, diabetes, cigarette smoking, alcohol consumption, exercise
frequency, body mass index, and height. During follow-up, coronary heart disease (CHD) occurred first in 1,348 men, stroke
in 902 men, and VTE in 358 men. Incidence of all three outcomes increased with age, but the rate of increase was strongest
for stroke. Hypertension, elevated cholesterol, diabetes, and smoking were associated with increased rates of CHD and stroke,
with comparable magnitudes, but had no association with VTE. Conversely, higher body mass index was more strongly associated
with risk of VTE than of either CHD or stroke, and taller men had a significantly increased risk of VTE but a lower risk of
CHD. CHD and stroke have broadly comparable risk factor profiles that differ widely from the profile for VTE.
Whether atherosclerotic disease predisposes to venous thrombosis is uncertain.
To determine whether subclinical atherosclerosis, manifested as increased carotid intima-media thickness (IMT) or presence of carotid plaque, is associated with increased incidence of venous thromboembolism (VTE).
The Atherosclerosis Risk in Communities study is a prospective cohort of adults aged 45-64 years, examined at baseline (1987-89) and followed for cardiovascular events. Bilateral carotid ultrasound for IMT measurements was done at baseline for portions of the common and internal carotid arteries, and carotid bifurcation and also to detect the presence of carotid plaque. Exclusion criteria included baseline anticoagulant use, history of coronary heart disease, stroke, or VTE, and incomplete data. First VTE during follow-up was validated using abstracted medical records.
Among 13,081 individuals followed for a mean of 12.5 years, 225 first VTE events were identified. Unadjusted hazard ratios (HR) (95% CI) of VTE across quartiles of baseline IMT were 1.0, 1.16 (0.77-1.75), 1.64 (1.12-2.40), and 1.52 (1.03-2.25). However, this association disappeared after adjustment for age, sex, and ethnicity (HRs: 1.0, 1.06, 1.40, and 1.18). Further adjustment for body mass index and diabetes weakened the relative risks even further. Presence of carotid plaque at baseline also was not associated with VTE occurrence; adjusted HR = 0.97, 95% CI = 0.72-1.29.
Increased carotid IMT or presence of carotid plaque was not associated with an increased incidence of VTE in this middle-aged cohort, suggesting subclinical atherosclerosis itself is not a VTE risk factor.
The results of studies investigating the relationship of smoking with venous thrombosis are inconsistent. Therefore, in the MEGA study, a large population-based case-control study, we evaluated smoking as a risk factor for venous thrombosis and the joint effect with oral contraceptive use and the factor V Leiden mutation. Consecutive patients with a first venous thrombosis were included from six anticoagulation clinics. Partners of patients were asked to participate and additional controls were recruited using a random digit dialing method. Participants completed a standardized questionnaire. Individuals with known malignancies were excluded from the analyses, leaving a total of 3,989 patients and 4,900 controls. Current and former smoking resulted in a moderately increased risk of venous thrombosis (odds ratio (OR)(current) 1.43, 95% confidence interval (CI95) 1.28-1.60, OR(former) 1.23, CI95 1.09-1.38) compared with nonsmoking. Adjustment for fibrinogen levels did not substantially change these risk estimates. A high number of pack-years resulted in the highest risk among young current smokers (OR(>or=20 pack-years) 4.30, CI95 2.59-7.14) compared with young nonsmokers. Women who were current smokers and used oral contraceptives had an 8.8-fold higher risk (OR 8.79, CI95 5.73-13.49) than nonsmoking women who did not use oral contraceptives. Relative to nonsmoking noncarriers, the joint effect of factor V Leiden and current smoking led to a 5.0-fold increased risk; for the prothrombin 20210A mutation this was a 6.0-fold increased risk. In conclusion, smoking appears to be a risk factor for venous thrombosis with the greatest relative effect among young women using oral contraceptives.
In some studies, venous thromboembolism has been associated with atherosclerosis and with the risk of arterial cardiovascular events such as myocardial infarction and stroke. Other studies, however, do not show this association. To help clarify these discrepant findings, we aimed to investigate the risk of arterial cardiovascular events in patients who were diagnosed with venous thromboembolism.
We undertook a 20-year population-based cohort study using data from nationwide Danish medical databases. After excluding those with known cardiovascular disease, we assessed the risk of myocardial infarction and stroke in 25,199 patients with deep venous thrombosis, 16,925 patients with pulmonary embolism, and 163,566 population controls.
For patients with deep venous thrombosis, the relative risks varied from 1.60 for myocardial infarction (95% CI 1.35-1.91) to 2.19 (1.85-2.60) for stroke in the first year after the thrombotic event. For patients with pulmonary embolism, the relative risks in that year were 2.60 (2.14-3.14) for myocardial infarction and 2.93 (2.34-3.66) for stroke. The relative risks were also raised, though less markedly, during the subsequent 20 years of follow-up, with 20-40% increases in risk for arterial cardiovascular events. Relative risks were similar for those with provoked and unprovoked deep venous thrombosis and pulmonary embolism.
Patients with venous thromboembolism have a substantially increased long-term risk of subsequent arterial cardiovascular events.
The link between psychosocial factors and coronary heart disease is well established, but although effects on coagulation and fibrinolysis variables may be implicated, no population-based study has sought to determine whether venous thromboembolism is similarly related to psychosocial factors.
To determine whether venous thromboembolism (deep vein thrombosis or pulmonary embolism) is related to psychosocial factors.
A stress questionnaire was filled in by 6958 men at baseline from 1970 to 1973, participants in a cardiovascular intervention trial. Their occupation was used to determine socio-economic status.
After a maximum follow-up of 28.8 years, 358 cases of deep vein thrombosis and/or pulmonary embolism were identified through the Swedish hospital discharge and cause-specific death registries. In comparison with men who, at baseline, had no or moderate stress, men with persistent stress had increased risk of pulmonary embolism [hazard ratio (HR)=1.80, 95% CI: 1.21-2.67]. After multivariable adjustment, the HR decreased slightly to 1.66 (95% CI: 1.12-2.48). When compared with manual workers, men with white-collar jobs at intermediate or high level and professionals showed an inverse relationship between occupational class and pulmonary embolism (multiple-adjusted HR=0.57, 95% CI: 0.39-0.83). Deep vein thrombosis was not significantly related to either stress or occupational class.
Both persistent stress and low occupational class were independently related to future pulmonary embolism. The mechanisms are unknown, but effects on coagulation and fibrinolytic factors are likely.
33 Royal College of Physicians Nicotine Addiction in Britain: a Report of the Tobacco Advisatory Group of the Royal College of Physicians
33 Royal College of Physicians. Nicotine Addiction in Britain: a Report of
the Tobacco Advisatory Group of the Royal College of Physicians.
London: Royal College of Physicians; 2000.
Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study 20 WHO Tobacco Free Initiative. The role of health professionals in tobacco control
- Ag Holst
- G Jensen
- E Prescott
Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation
2010; 121: 1896–903.
20 WHO Tobacco Free Initiative. The role of health professionals in
tobacco control. Geneva: World Health Organization, 2005.
Cigarette smokingattributable morbidity -United States
Centers for Disease Control and Prevention. Cigarette smokingattributable morbidity -United States, 2000. MMWR 2003; 52: 842-4.
Annual smokingattributable mortality, years of potential life lost, and economic costs -United States
Centers for Disease Control and Prevention. Annual smokingattributable mortality, years of potential life lost, and economic costs -United States, 1995-1999. MMWR. 2002;51:300-3.
The role of health professionals in tobacco control. Geneva: World Health Organization
- Who Tobacco Free Initiative
WHO Tobacco Free Initiative. The role of health professionals in
tobacco control. Geneva: World Health Organization, 2005.
Percentage daily smokers and occasional smokers, by sex
- Statistics Norway
Statistics Norway. Percentage daily smokers and occasional
smokers, by sex. 2011. http://statbank.ssb.no//statistikkbanken/
default_fr.asp?PLanguage=1. Accessed 23 May 2011.
Annual smoking - attributable mortality, years of potential life lost, and economic costs - United States, 1995-1999
- Centers for Disease Control and Prevention