No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Coffee consumption is associated with a reduced risk of venous thrombosis that is mediated through hemostatic factor levels
Abstract
Background:
Coffee consumption is associated with a lower risk of venous thrombosis, but the role of confounding and the pathophysiology behind these findings are unclear.
Objective:
To assess the role of hemostatic factors in the relationship between coffee consumption and venous thrombosis.
Methods:
From a large case-control study, 1803 patients with a first venous thrombosis and 1803 partner controls were included. With conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for venous thrombosis were calculated for coffee consumption vs. no coffee consumption. In addition, mean differences in hemostatic factor levels between these groups were calculated in the controls.
Results:
Coffee consumption yielded a 30% lower risk of venous thrombosis than no coffee consumption (OR 0.7, 95% CI 0.5-0.9). Adjustment for several putative confounders (age, sex, body mass index, smoking, hormonal factors, statin, aspirin, alcohol, malignancy, and chronic disease) yielded an OR of 0.8 (95% CI 0.6-1.1). Results were similar for provoked and unprovoked events, and for deep vein thrombosis and pulmonary embolism. In controls, von Willebrand factor levels were 11 (3-19) IU dL(-1) lower and factor (F) VIII levels were 11 (1-21) IU dL(-1) lower in coffee consumers than in non-consumers. After adjustment of the risk estimates for these hemostatic factors, the inverse association between coffee consumption and venous thrombosis diminished (OR 1.0, 95% CI 0.7-1.4). There was no association between coffee consumption and anticoagulant proteins, fibrinogen levels, or fibrinolytic markers.
Conclusions:
Coffee consumption is associated with a lower risk of venous thrombosis, which seems to be mediated through von Willebrand factor and FVIII.
... In contrast, an earlier experiment demonstrated an immediate increase in fibrinolytic activity upon coffee intake [28]. A recent study discovered reduced levels of von Willebrand factor and factor VIII among coffee drinkers, but found no association with fibrinogen or anticoagulant proteins [29]. These disparate results highlight the complexity of the relationship between coffee and hemostatic factors. ...
This study aimed to explore the potential link between coffee and tea consumption and the risk of deep vein thrombosis (DVT) through Mendelian randomization (MR) analysis. Employing the MR, we identified 33 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for coffee intake and 38 SNPs for tea intake. The investigation employed the inverse-variance weighted (IVW) method to evaluate the causal impact of beverage consumption on DVT risk. Additionally, MR-Egger and MR-PRESSO tests were conducted to assess pleiotropy, while Cochran’s Q test gauged heterogeneity. Robustness analysis was performed through a leave-one-out approach. The MR analysis uncovered a significant association between coffee intake and an increased risk of DVT (odds ratio [OR] 1.008, 95% confidence interval [CI] = 1.001–1.015, P = 0.025). Conversely, no substantial causal effect of tea consumption on DVT was observed (OR 1.001, 95% CI = 0.995–1.007, P = 0.735). Importantly, no significant levels of heterogeneity, pleiotropy, or bias were detected in the instrumental variables used. In summary, our findings suggest a modestly heightened risk of DVT associated with coffee intake, while tea consumption did not exhibit a significant impact on DVT risk.
... The consumption of coffee purine-like alkaloids such as caffeine reduced the risk of venous thrombosis (30% lower risk) compared with the no coffee consumption group. These results seem to be associated with lowering hemostatic factors, including the von Willebrand factor and FVIII, in coffee consumers [101]. ...
Thromboembolism is the third leading vascular disease, with a high annual incidence of 1 to 2 cases per 1000 individuals
within the general population. The broader term venous thromboembolism generally refers to deep vein thrombosis, pulmonary embolism, and/or a combination of both. Therefore, thromboembolism can affect both – the central and peripheral veins.
Arterial thromboembolism causes systemic ischemia by disturbing blood flow and oxygen supply to organs, tissues, and cells
causing, therefore, apoptosis and/or necrosis in the affected tissues. Currently applied antithrombotic drugs used, e.g. to protect affected individuals against ischemic stroke, demonstrate significant limitations. For example, platelet inhibitors possess
only moderate efficacy. On the other hand, thrombolytics and anticoagulants significantly increase hemorrhage. Contextually, new approaches are extensively under consideration to develop next-generation antithrombotics with improved efficacy and
more personalized and targeted application. To this end, phytochemicals show potent antithrombotic efficacy demonstrated in numerous in vitro, ex vivo, and in vivo models as well as in clinical evaluations conducted on healthy individuals and persons at high risk of thrombotic events, such as pregnant women (primary care), cancer, and COVID-19-affected patients (secondary and tertiary care). Here, we hypothesized that specific antithrombotic and antiplatelet efects of plant-derived compounds might be of great clinical utility in primary, secondary, and tertiary care. To increase the efficacy, precise patient
stratification based on predictive diagnostics is essential for targeted protection and treatments tailored to the person in the framework of 3P medicine. Contextually, this paper aims at critical review toward the involvement of specific classes of phytochemicals in antiplatelet and anticoagulation adapted to clinical needs. The paper exemplifies selected plant-derived drugs, plant extracts, and whole plant foods/herbs demonstrating their specific antithrombotic, antiplatelet, and fibrinolytic activities relevant for primary, secondary, and tertiary care. One of the examples considered is antithrombotic and antiplatelet protection specifically relevant for COVID-19-affected patient groups.
... In a study on venous thrombosis, coffee consumers had lower coagulation factor VIII levels and a lower risk of thrombosis than nonconsumers. 29 A possible explanation could be that the anti-inflammatory properties of coffee and their effect on endothelial cells and thrombocytes lowers the level of the von Willebrand Factor which is in complex with factor VIII. 30 Although changes in hemostatic factors do not directly cause bleeding but rather turn a small bleed caused by the underlying small vessel disease into a large bleed, this might trigger ICH in patients with underlying small vessel disease. For straining, vigorous exercise, sexual activity, and heavy lifting, an increase in blood pressure also seems the likely pathophysiological process causing onset of ICH. ...
Background and purpose:
Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge on the pathophysiology of ICH. We assessed potential trigger factors and their risk for ICH onset.
Methods:
We included consecutive patients diagnosed with ICH between July 1, 2013, and December 31, 2019. We interviewed patients on their exposure to 12 potential trigger factors (eg, Valsalva maneuvers) in the (hazard) period soon before onset of ICH and their normal exposure to these trigger factors in the year before the ICH. We used the case-crossover design to calculate relative risks (RR) for potential trigger factors.
Results:
We interviewed 149 patients (mean age 64, 66% male) with ICH. Sixty-seven (45%) had a lobar hemorrhage, 60 (40%) had a deep hemorrhage, 19 (13%) had a cerebellar hemorrhage, and 3 (2%) had an intraventricular hemorrhage. For ICH in general, there was an increased risk within an hour after caffeine consumption (RR=2.5 [95% CI=1.8-3.6]), within an hour after coffee consumption alone (RR=4.8 [95% CI=3.3-6.9]), within an hour after lifting >25 kg (RR=6.6 [95% CI=2.2-19.9]), within an hour after minor head trauma (RR=10.1 [95% CI=1.7-60.2]), within an hour after sexual activity (RR=30.4 [95% CI=16.8-55.0]), within an hour after straining for defecation (RR=37.6 [95% CI=22.4-63.4]), and within an hour after vigorous exercise (RR=21.8 [95% CI=12.6-37.8]). Within 24 hours after flu-like disease or fever, the risk for ICH was also increased (RR=50.7 [95% CI=27.1-95.1]). Within an hour after Valsalva maneuvers, the RR for deep ICH was 3.5 (95% CI=1.7-6.9) and for lobar ICH the RR was 2.0 (95% CI=0.9-4.2).
Conclusions:
We identified one infection and several blood pressure related trigger factors for ICH onset, providing new insights into the pathophysiology of vessel rupture resulting in ICH.
... Alcohol consumption was not related to VTE in studies encompassing both women and men [11], whereas whether this association exists in women or men separately is inconclusive [11][12][13]. Data on coffee consumption [13][14][15] and diet [13,16,17] in relation to VTE are limited or conflicting. Although physical activity as a whole was inversely associated with VTE risk, the association of daily leisure time activity with VTE might differ due to the heterogeneity in types and amount of different physical activities [9]. ...
Introduction
Evidence on the associations of lifestyle factors with venous thromboembolism (VTE) is inconsistent. We aimed to investigate the associations of modifiable lifestyle factors with VTE in women and men.
Methods
We used data from two cohorts comprising 30,137 women and 36,193 men aged over 45 years and free of cancer and VTE. Information on lifestyle factors was collected in 1997 via a self-administrated questionnaire. VTE cases were ascertained by linkage with the National Patient Register until the end of 2019.
Results
During a mean of 16.9-years follow-up, 1784 women and 2043 men were diagnosed with VTE. Compared with individuals with <10 min/day of physical activity, the multivariable hazard ratios (HRs) of VTE were 0.67 (95% confidence interval (CI), 0.58, 0.79) and 0.78 (95% CI, 0.67, 0.92) in women and men with >60 min/day, respectively. Compared with individuals with the lowest adherence to a modified Dietary Approaches to Stop Hypertension diet, the multivariable HRs of VTE were 0.87 (95% CI, 0.75, 0.99) and 0.88 (95% CI, 0.80, 1.00) for women and men with the highest adherence. In women, the multivariable HRs of VTE were 1.16 (95% CI, 1.03, 1.29) for past smoker and 1.28 (95% CI, 1.14, 1.45) for current smoker compared with never smoker. Alcohol and coffee consumption were not associated with VTE.
Conclusions
This study suggests that being physically active and adhering to a healthy diet may lower the risk of VTE in women and men. Cigarette smoking was positively associated with VTE in women.
Background
Hemostatic abnormality has contributed to vascular access thrombosis in patients with chronic kidney disease (CKD). Previous studies have demonstrated that far-infrared radiation (FIR) therapy can maintain the patency and maturity of arteriovenous fistulas of patients undergoing hemodialysis (HD). However, prolonged access bleeding is observed once FIR is conducted at the end of dialysis. FIR can block the binding of platelet and von Willebrand factor (vWF), a predictor of hemostatic abnormality and vascular access thrombosis. However, clinical studies exploring FIR and vWF are sparse.
Methods
We recruited 20 HD patients, 21 CKD patients, and 20 controls to examine the alteration of vWF and a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) following a single 40-min session of FIR therapy. In addition, the alteration of these factors in the HD group was examined following a 40-min FIR session thrice a week for 3 months.
Results
A decreasing trend in the vWF activity-antigen ratio of participants in all groups following a single FIR session was observed. In addition, the ratio in the HD group was significantly lower following 3 months of FIR therapy. The subgroup analysis revealed a consistent trend and multiple regression analysis showed that participants not taking hydroxymethylglutaryl-coenzyme A reductase inhibitor, diabetes mellitus, and higher hemoglobin levels were the significant factors. The alteration of the vWF activity-antigen ratio correlated moderately to that of ADAMTS13 antigen and activity.
Conclusion
FIR may alter the ratio of ultra-large vWF multimers through ADAMTS13, contributing to inhibiting platelet-endothelium interactions of CKD patients.
Caffeine is a secondary metabolite extensively studied for its stimulatory properties and presumed association with specific pathologies. This alkaloid is typically consumed through coffee, tea, and other plant products but is also an additive in many medications and confectionaries. Nonetheless, despite its worldwide consumption and acceptance, there is controversial evidence as to whether its effects on the central nervous system should be interpreted as stimulatory or as an addiction in which typical withdrawal effects are canceled out with its daily consumption. The following discussion is the product of an extensive review of current scientific literature, which aims to describe the most salient topics associated with caffeine's purpose in nature, biosynthesis, metabolism, physiological effects, toxicity, extraction, industrial use and current plant breeding approaches for the development of new caffeine deficient varieties as a more economical option to the industrially decaffeinated coffees currently available to caffeine intolerant consumers. Keywords: biosynthesis, decaffeination, extraction, metabolism, physiological effects, plant breeding.
Impact of coffee consumption on risk of venous thromboembolism (VTE) is not extensively studied. To date, three observational studies have investigated the relation between coffee intake and risk of VTE, and all of these studies point toward an inverse association, i.e., coffee consumption seems to protect against VTE. However, these findings must be interpreted with caution because observational studies are subject to confounding and bias. Potential mechanisms for the inverse association between coffee intake and risk of VTE are not fully elucidated. Polyphenols in coffee may promote favorable alterations in the coagulation- and fibrinolytic systems, platelet functions, and endothelial functions that may protect against VTE. Overall, more epidemiological and mechanistic studies are warranted to determine the underlying mechanism(s) for the inverse relation between coffee consumption and risk of VTE.
Background: Among the various risk factors of venous thromboembolism (VTE), nutrients seem to play a significant role in the pathogenesis of this condition. This study aimed to clarify the relationship between coffee intake and venous thrombosis, and we performed a critical review of clinical studies that have been published so far.
Methods: An electronic search was carried out in Medline, Scopus and ISI Web of Science with the keywords “coffee” AND “venous thromboembolism” OR “deep vein thrombosis” OR “pulmonary embolism” in “Title/Abstract/Keywords”, with no language and date restriction.
Results: According to our criteria, three studies (two prospective and one case-control) were finally selected (inter-study heterogeneity: 78%; P<0.001). Cumulative data suggests that a modest intake of coffee (i.e., 1-4 cups/day) may be associated with an 11% increased risk of VTE compared to abstainers, whereas a larger intake (i.e., ≥5 coffee/day) may be associated with a 25% decreased risk.
Conclusions: Our analysis of published data seemingly confirm the existence of a U-shape relationship between coffee intake and VTE, thus exhibiting a trend that overlaps with that previously reported for cardiovascular disease (CVD).
Thrombosis is a complex human disease. It is the result of the interaction between the environment and genes. This interaction is manifested by «intermediary phenotypes». These intermediary phenotypes are useful for estimating the risk of developing the disease. The targets of current investigations are attempting to identify new mechanisms that underlie the classic Virchow's triad. Modern methodologies, such as genome wide association studies (GWAS) and high-throughput genotyping technology (massive sequencing techniques) are being used to identify genetic variants. The fields of epigenetics, transcriptomics and metabolomics are being developed to complement these studies. The vast amount of data to explain the environmental and genetic factors that predispose for the disease require informatic techniques, such as mathematical and bio-computer models to estimate the individual risk of thrombosis. The research area with the highest clinical application is the development of predictive models to estimate the individual risk of thrombosis.
Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear.
We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline.
During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline.
In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.).
Coffee is one of the most popular and heavily consumed beverages worldwide, despite the many different methods of preparation and presentation. The results of several epidemiological studies are suggestive for the existence of a U-shaped relationship between coffee consumption and both cardiovascular events and mortality, whereby a lower risk seems associated with low (i.e., less than one cup per day) or high (i.e., more than or equal to four cups per day) coffee intake, whereas a higher risk is reported for intermediate consumption (i.e., two to four cups per day). Most benefits are evident in individuals with a rapid caffeine metabolizer genotype and a low baseline cardiovascular risk. Benefits have also been differentially associated with consumption of decaffeinated coffee, filtered coffee, coffee consumption during lunchtime or dinner, and when coffee is produced in the Italian style (i.e., by espresso or moka). The leading favorable effects have been attributed to various compounds present in coffee. Thus, chlorogenic acids would be effective in decreasing blood pressure, systemic inflammation, risk of type 2 diabetes, and platelet aggregation, whereas caffeine intake has instead been associated with decreased body weight, as well as with increased flow-mediated dilatation and fibrinolysis.
Studies have correlated elevated plasma factor VIII (FVIII) with thrombosis; however, it is unclear whether elevated FVIII is a proinflammatory biomarker, causative agent, or both. We raised FVIII levels in mice and measured the time to vessel occlusion (TTO) after ferric chloride-induced injury. Compared with control (saline-infused) mice, elevated FVIII had no effect after longer (3-minute) carotid artery injury, but it shortened the TTO after shorter (2-minute) injury (P < .008). After injury, circulating thrombin-antithrombin (TAT) complexes were lower after short versus long injury (P < .04), suggesting short treatment produced less coagulation activation. TAT levels in FVIII-infused mice were higher than in controls after short, but not longer, injury. Accordingly, elevated FVIII had no effect on in vitro thrombin generation or platelet aggregation triggered by high tissue factor, but it increased thrombin generation rate and peak (2.4- and 1.5-fold, respectively), and it accelerated platelet aggregation (up to 1.6-fold) when initiated by low tissue factor. Compared with control mice, elevated FVIII stabilized thrombi (fewer emboli) after short injury, but it had no effect after longer injury. TTO and emboli correlated with TATs. These results demonstrate dependence of FVIII activity on extent of vascular injury. We propose elevated plasma FVIII is an etiologic, prothrombotic agent after moderate but not extensive vascular damage.
We discuss the analytic and practical considerations in a large case-control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.
Coffee consumption is associated with a decreased risk of type 2 diabetes. Suggested mechanisms underlying the association have included attenuation of subclinical inflammation and a reduction in oxidative stress.
The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake, subclinical inflammation, oxidative stress, glucose, and lipid metabolism.
Habitual coffee drinkers (n = 47) refrained for 1 mo from coffee drinking; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d (150 mL/cup). Blood samples were analyzed by gas chromatography-mass spectrometry, bead-based multiplex technology, enzyme-linked immunosorbent assay, or immunonephelometry.
Coffee consumption led to an increase in coffee-derived compounds, mainly serum caffeine, chlorogenic acid, and caffeic acid metabolites. Significant changes were also observed for serum concentrations of interleukin-18, 8-isoprostane, and adiponectin (medians: -8%, -16%, and 6%, respectively; consumption of 8 compared with 0 cups coffee/d). Serum concentrations of total cholesterol, HDL cholesterol, and apolipoprotein A-I increased significantly by 12%, 7%, and 4%, respectively, whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8% and 9%, respectively (8 compared with 0 cups coffee/d). No changes were seen for markers of glucose metabolism in an oral-glucose-tolerance test.
Coffee consumption appears to have beneficial effects on subclinical inflammation and HDL cholesterol, whereas no changes in glucose metabolism were found in our study. Furthermore, many coffee-derived methylxanthines and caffeic acid metabolites appear to be useful as biomarkers of coffee intake.
Coffee is the most widely consumed beverage in the world, but its effect on the cardiovascular system has not been fully understood. Coffee contains caffeine and antioxidants, which may influence endothelial function, both of which have not yet been investigated. The objective of this study was to investigate the acute effects of coffee on endothelial function measured by brachial artery flow-mediated dilation (FMD).
A total of 20 (10 males and 10 females) healthy non-obese subjects underwent a double-blind, crossover study. Subjects ingested one cup of caffeinated (CC) and one cup of decaffeinated (DC) Italian espresso coffee in random order at 5- to 7-day intervals.
Following CC ingestion, FMD decreased progressively and significantly (mean+/-s.e.m.: 0 min, 7.7+/-0.6; 30 min, 6.3+/-0.7; 60 min, 6.0+/-0.8%; ANOVA (analysis of variance), P<0.05), but it did not significantly increase after DC ingestion (0 min, 6.9+/-0.6; 30 min, 8.1+/-0.9; 60 min, 8.5+/-0.9%; P=0.115). Similarly, CC significantly increased both systolic and diastolic blood pressure; this effect was not observed after DC ingestion. Blood glucose concentrations remained unchanged after ingestion of both CC and DC, but insulin (0 min, 15.8+/-0.9; 60 min, 15.0+/-0.8 muU/ml; P<0.05) and C-peptide (0 min, 1.25+/-0.09; 60 min, 1.18+/-0.09 ng/ml; P<0.01) blood concentrations decreased significantly only after CC ingestion.
CC acutely induced unfavorable cardiovascular effects, especially on endothelial function. In the fasting state, insulin secretion is also likely reduced after CC ingestion. Future studies will determine whether CC has detrimental clinically relevant effects, especially in unhealthy subjects.
A positive family history of venous thrombosis may reflect the presence of genetic risk factors. Once a risk factor has been identified, it is not known whether family history is of additional value in predicting an individual's risk. We studied the contribution of family history to the risk of venous thrombosis in relation to known risk factors.
In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis, a population-based case-control study, we collected blood samples and information about family history and environmental triggers from 1605 patients with a first venous thrombosis and 2159 control subjects.
A total of 505 patients (31.5%) and 373 controls (17.3%) reported having 1 or more first-degree relatives with a history of venous thrombosis. A positive family history increased the risk of venous thrombosis more than 2-fold (odds ratio [95% confidence interval], 2.2 [1.9-2.6]) and up to 4-fold (3.9 [2.7-5.7]) when more than 1 relative was affected. Family history corresponded poorly with known genetic risk factors. Both in those with and without genetic or environmental risk factors, family history remained associated with venous thrombosis. The risk increased with the number of factors identified; for those with a genetic and environmental risk factor and a positive family history, the risk was about 64-fold higher than for those with no known risk factor and a negative family history.
Family history is a risk indicator for a first venous thrombosis, regardless of the other risk factors identified. In clinical practice, family history may be more useful for risk assessment than thrombophilia testing.
Risk of venous thrombosis is increased after long-distance travel. Identifying high-risk groups may provide a basis for targeted prevention. We assessed the effect of increased levels of coagulation factors and combinations of risk factors in travelers in a large case-control study. We calculated odds ratios (ORs) for 334 travelers (200 cases and 134 controls) with coagulation factors II (prothrombin), VII, VIII, and IX; fibrinogen, and von Willebrand factor (VWF) above the 80th percentile; for increasing numbers of risk factors; and for specific combinations. The risk was increased in travelers with high FII (OR, 2.2: 95% CI, 1.3-3.7) and FVIII (OR, 6.2, (95% CI, 3.6-10.5) compared with travelers with normal levels. High FIX and fibrinogen levels increased the risk in air travelers (FIX: OR, 3.2; 95% CI, 0.9-11.0; fibrinogen: OR, 2.0; 95% CI, 0.7-5.5) but not in other travelers. The ORs increased with the number of risk factors, and the risk was increased most in women with the combination of oral contraceptives and high FVIII (OR, 51.7; 95% CI, 5.4-498). We conclude that increased levels of FII and FVIII increase the risk of venous thrombosis in travelers. Furthermore, the risk is greatly increased if other risk factors are present as well.
The role of the fibrinolytic system in the development of deep vein thrombosis (DVT) is unclear. We determined the plasma fibrinolytic potential of patients enrolled in the Leiden Thrombophilia Study (LETS), a population-based case-control study on risk factors for DVT. Plasma fibrinolytic potential was determined in 421 patients and 469 control subjects by means of a tissue factor-induced and tissue-type plasminogen activator (tPA)-induced clot lysis assay. Using clot lysis times above the 70th, 80th, 90th, 95th, and 99th percentiles of the values found in control subjects as cut-off levels, we found a dose-dependent increase in risk for DVT in patients with hypofibrinolysis (odds ratios of 1.4, 1.6, 1.9, 2.1, and 2.2, respectively). This indicates a 2-fold increased risk of DVT in subjects with clot lysis times above the 90th percentile. The risk increase was not affected by age or sex (adjusted odds ratio for 90th percentile, 2.0), and after correction for all possible confounders (age, sex, and levels of procoagulant proteins shown to associate with clot lysis times in the control population), the risk estimate was marginally reduced (odds ratio, 1.6 for 90th percentile). Taken together, these results indicate that plasma hypofibrinolysis constitutes a risk factor for venous thrombosis, with a doubling of the risk at clot lysis times that are present in 10% of the population.
Rothman discusses a new study by Cannegieter and colleagues which looked at the interaction of lengthy travel with other risk factors for venous thromboembolism.
In several short-term studies, coffee consumption has been associated with impairment of endothelial function.
The objective was to assess the relation between long-term caffeinated and decaffeinated filtered coffee consumption and markers of inflammation and endothelial dysfunction.
We conducted a cross-sectional study of 730 healthy women and 663 women with type 2 diabetes from the Nurses' Health Study I cohort, who were aged 43-70 y and free of cardiovascular disease and cancer at the time blood was drawn (1989-1990). Dietary intake was assessed with a validated food-frequency questionnaire in 1986 and 1990.
About 77% of the healthy women consumed > or =1 cup (237 mL) caffeinated coffee/mo and 75% consumed > or =1 cup decaffeinated coffee/mo; the corresponding intakes for women with type 2 diabetes were 74% and 63%, respectively. In healthy women, no appreciable differences in plasma concentrations of the markers were found across categories of caffeinated coffee intake. In women with type 2 diabetes, higher caffeinated coffee consumption was associated with lower plasma concentrations of E-selectin (adjusted percentage change per 1 cup/d increment = -3.2%; P = 0.05) and C-reactive protein (adjusted percentage change = -10.2%; P < 0.001). Higher decaffeinated coffee consumption was associated with lower plasma concentrations of E-selectin (adjusted percentage change = -2.5%; P = 0.08) and C-reactive protein (adjusted percentage change = -7.9%; P = 0.02) only in healthy women. The results were similar when we also adjusted the models for other dietary factors and blood lipids and when we excluded participants with hypertension or hypercholesterolemia.
These results indicate that neither caffeinated nor decaffeinated filtered coffee has a detrimental effect on endothelial function. In contrast, the results suggest that coffee consumption is inversely associated with markers of inflammation and endothelial dysfunction.
Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.
Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors. Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.
The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.
Introduction
The reader will find here a concise summary of established notions on the structure and function of von Willebrand factor (vWF), followed by a brief discussion of selected recent advances that illustrate how this molecule supports platelet function in hemostasis and thrombosis. A comprehensive review of the topic is beyond the scope of this chapter and may be found elsewhere.1-3
Coffee is a major source of caffeine, which has been shown to acutely reduce sensitivity to insulin, but also has potentially beneficial effects. We prospectively investigated the association between coffee consumption and risk of clinical type 2 diabetes in a population-based cohort of 17 111 Dutch men and women aged 30-60 years. During 125 774 person years of follow-up, 306 new cases of type 2 diabetes were reported. After adjustment for potential confounders, individuals who drank at least seven cups of coffee a day were 0-50 (95% CI 0.35-0.72, p=0.0002) times as likely as those who drank two cups or fewer a day to develop type 2 diabetes. Coffee consumption was associated with a substantially lower risk of clinical type 2 diabetes.
We determined in a prospective cohort of patients treated with vitamin K antagonists for venous thrombosis, the course of factor VIII (FVIII:C), C-reactive protein (CRP) and fibrinogen levels, to assess the influence of the acute phase reaction on FVIII:C levels. Second, we hypothesized that patients with preceding infectious symptoms might have higher levels of FVIII:C at baseline than patients without those. We included 75 patients. Blood was sampled at baseline, once during treatment (t=1) and at the end of treatment (t=2). Mean levels of FVIII:C were 207, 186 and 175IU/dL (p for trend 0.003) at baseline, t=1 and t=2 respectively. Eight-eight percent of patients had an elevated FVIII:C at baseline, 75% at t=1 and 72% at t=2 (p for trend 0.045). Mean levels of FVIII:C were not different in patients with or without preceding infectious symptoms (206 versus 205IU/dL respectively). A baseline CRP level below 62mg/L could best distinguish between patients who will keep an elevated FVIII:C and those who will drop below 150IU/dL. We conclude that FVIII:C levels are partially influenced by the acute phase reaction, especially in patients who keep a persistent elevated FVIII:C during treatment. Preceding infectious symptoms did not influence baseline FVIII:C levels.
Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective
studies to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified
by searching PubMed and Embase from January 1966 through May 2011 and by reviewing the reference lists of retrieved articles.
Prospective studies in which investigators reported relative risks of stroke for 3 or more categories of coffee consumption
were eligible. Results from individual studies were pooled using a random-effects model. Eleven prospective studies, with
10,003 cases of stroke and 479,689 participants, met the inclusion criteria. There was some evidence of a nonlinear association
between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval
(95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3−4 cups/day, 0.87 (95% CI: 0.77, 0.97)
for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day. There was marginal between-study heterogeneity among study-specific
trends (I2 = 12% and I2 = 20% for the first and second spline transformations, respectively). Findings from this meta-analysis indicate that moderate
coffee consumption may be weakly inversely associated with risk of stroke.
Several studies have investigated the association between coffee consumption and cardiovascular disease, but little is known about coffee intake and the risk of venous thromboembolism (VTE).
The aim of this prospective cohort study was to investigate the association between coffee consumption and the risk of incident VTE in a general population.
Information about coffee consumption habits was obtained with a self-administered questionnaire in 26, 755 subjects, aged 25-97 years, who participated in the fourth survey of the Tromsø study (1994-1995). Incident VTE events were registered until the end of follow-up, 1 September 2007.
There were 462 incident VTE events (1.60 per 1000 person-years, 95% confidence interval [CI] 1.46-1.75) during a median of 12.5 years of follow-up. A daily consumption of three to four cups was borderline associated (hazard ratio [HR] 0.70; 95% CI 0.48-1.02) and a daily consumption of five to six cups (HR 0.67; 95% CI 0.45-0.97) was significantly associated with reduced risk of VTE as compared with coffee abstainers in multivariable analysis adjusted for age, sex, body mass index (BMI), smoking status, physical activity, diabetes, history of cardiovascular disease and cancer. Similar risk estimates were found for provoked and unprovoked VTE, and in sex-stratified analyses.
Our findings suggest a possible U-shaped relationship between coffee consumption and VTE, and that moderate coffee consumption may be associated with a reduced risk of VTE. However, more studies are needed to establish whether moderate coffee consumption is inversely associated with the risk of VTE.
Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers.
Little is known about the role of diet in the development of venous thromboembolism (VTE). We explored the prospective relation of dietary patterns, food groups, and nutrients to incident VTE in older women.
In 1986, Iowa women aged 55 to 69 years completed a mailed survey, including a 127-item food frequency questionnaire. These data were linked to Medicare data from 1986 to 2004, and International Classification of Diseases discharge codes were used to identify hospitalized VTE cases. Cox regression analyses evaluated relations of 2 principal components-derived dietary patterns, 11 food groups, and 6 nutrients to VTE, adjusted for age, education, smoking status, physical activity, and energy intake.
Over 19 years of follow-up, 1,950 of the 37,393 women developed VTE. Women consuming alcohol daily were at 26% (95% CI 11%-38%) lower risk of VTE as compared to nonconsumers. All alcoholic beverages types were in the direction of lower risk; however, only beer and liquor were statistically significant. After basic adjustments, coffee was inversely related to VTE, and diet soda and fish positively related. However, these associations were confounded and became nonsignificant after adjustment for body mass index and diabetes. No associations were observed with consumption of 'Western' or 'Prudent' dietary patterns, fruit, vegetables, dairy, meat, refined grains, whole grains, regular soda, vitamins E, vitamin B6, vitamin B12, folate, omega-3 fatty acids, or saturated fat.
In this cohort of older women, greater intake of alcohol was associated with a lower risk of incident VTE. No other independent associations were seen between diet and VTE.
alpha-Granules are essential to normal platelet activity. These unusual secretory granules derive their cargo from both regulated secretory and endocytotic pathways in megakaryocytes. Rare, inheritable defects of alpha-granule formation in mice and man have enabled identification of proteins that mediate cargo trafficking and alpha-granule formation. In platelets, alpha-granules fuse with the plasma membrane upon activation, releasing their cargo and increasing platelet surface area. The mechanisms that control alpha-granule membrane fusion have begun to be elucidated at the molecular level. SNAREs and SNARE accessory proteins that control alpha-granule secretion have been identified. Proteomic studies demonstrate that hundreds of bioactive proteins are released from alpha-granules. This breadth of proteins implies a versatile functionality. While initially known primarily for their participation in thrombosis and hemostasis, the role of alpha-granules in inflammation, atherosclerosis, antimicrobial host defense, wound healing, angiogenesis, and malignancy has become increasingly appreciated as the function of platelets in the pathophysiology of these processes has been defined. This review will consider the formation, release, and physiologic roles of alpha-granules with special emphasis on work performed over the last decade.
A large amount of cohort studies addressed coffee consumption and risk of coronary heart disease (CHD) and yielded inconsistent results. We conducted a meta-analysis to estimate the pooling effects.
We searched for all published English articles indexed in MEDLINE or PubMed from January 1966 to January 2008. Twenty-one independent prospective cohort studies, which tested CHD risk by coffee consumption, were identified. A general variance-based method was used to pool the relative risks (RR). 15,599 cases from 407,806 participants were included in pooling the overall effects.
As compared to the light coffee consumption (<1 cup/d in US or <or=2 cups/d in Europe), under the random-effects model, the pooled CHD RRs (95% CI) for all studies combined were 0.96 (0.87-1.06), 1.04 (0.92-1.17) and 1.07 (0.87-1.32) for the moderate (1-3 or 3-4 cups/d), heavy (4-5 or 5-6 cups/d) and very heavy (>or=6 or >or=7 cups/d) categories of coffee consumption (all p>0.05); Moderate coffee consumption showed significantly lower CHD RR (95% CI) of 0.82 (0.73-0.92) (p<0.001) in women, and of 0.87 (0.80-0.86) (p=0.001) in men and women followed <or=10 years.
Our findings do not support the hypothesis that coffee consumption increases the long-term risk of coronary heart disease. Habitual moderate coffee drinking was associated with a lower risk of CHD in women.
Ingestion of coffee was followed after one-half and one hour by shortening of whole blood fibrinolysis time. The amount of coffee was equivalent to a heaped teaspoonsful and a standard brand of instant coffee was tested. The effect was laregly lost when decaffeinated coffee was taken. It appears that the caffeine in the amounts of coffee ordinarily consumed stimulates fibrinolytic activity but 2 of the 12 subjects were resistant to the effect.
The influence of coffee and caffeine consumption on hemostatic factors was studied in 2 randomized trials. Both studies were conducted in young, healthy adults. In the first study, 107 participants were randomly allocated to one or 3 intervention groups, drinking filtered coffee, boiled coffee or no coffee at all, respectively, for a period of 9 weeks. In the second study, 69 subjects received either 4-6 tablets containing 75 mg caffeine or the same amount of placebo tablets, while using decaffeinated coffee. In this double-blind study caffeine intake from any other source was not allowed. Blood samples for hemostatic factors were obtained at baseline and after 9 weeks of intervention. The findings indicate no effect of coffee consumption on fibrinogen, clotting factor VII activity, factor VIII antigen, protein C and protein S and also no effect of caffeine consumption on fibrinogen and factor VII activity.
Factor VIII activity (factor VIII:C) levels > or =150 IU/dl are associated with a 5- to 6-fold increased risk of venous thrombosis compared to levels <100 IU/dl, and fibrinogen levels > or =5.0 g/l increase the thrombosis risk 4-fold. These high levels are present in 25% resp. 3% of the patients with a first episode of venous thrombosis. These findings were based on measurements after the thrombotic event, so the factor VIII and fibrinogen levels in thrombosis patients may have been influenced by acute phase reactions or ongoing inflammatory responses. In the present study we measured plasma C-reactive protein (CRP) as a sensitive marker of an acute phase reaction in 474 thrombosis patients and 474 age- and sex-matched healthy controls, that were part of the Leiden Thrombophilia Study (LETS). Mean and median CRP levels were higher in thrombosis patients than in the controls, suggesting inflammation in some patients. CRP affected both factor VIII and fibrinogen levels, in patients and controls alike. After adjustment for the effect of CRP, high factor VIII:C levels still increased the thrombosis risk 6-fold and high fibrinogen levels 4-fold, which is for both very similar to the risk before correction for CRP levels. These results show that although systemic inflammation may be present in some of the patients, elevated levels of factor VIII:C and fibrinogen were in general not caused by acute phase reactions. This further supports a causal relationship between both high factor VIII:C and fibrinogen levels and venous thrombosis.
Recent literature has suggested a role for elevated FVIII:C in venous thromboembolic disease (VTED). However since FVIII:C is known to rise in response to an acute phase reaction, it is difficult to determine whether the increased FVIII:C precedes the thrombosis or represents a secondary reactive phenomenon. In an attempt to address this question, we followed 35 patients with confirmed VTED, raised FVIII:C level (>1.5 iu/ml) and no other thrombotic tendency. Serial measurements of FVIII:C, vWF:Ag, C-reactive protein and fibrinogen were performed. We hypothesized that a persistent increase in FVIII:C in the absence of any other measures of ongoing acute phase response, would support the idea that elevation of FVIII:C is a constitutional phenomenon.
Of this initial group, 94% continued to have an elevated FVIII:C level throughout the period of follow up (median 8 months; range 3 to 39 months), with no significant difference between the FVIII:C levels determined at first estimation and those obtained during follow up (p = 0.58). Conversely, only 18% had evidence of an acute phase reaction when first assessed, and nonparametric ranking analysis demonstrated no correlation between FVIII:C and either C-reactive protein or fibrinogen (p = 0.315 and 0.425 respectively).We conclude that increased FVIII:C levels following VTED are persistent, independent of the acute phase reaction, and thus may represent a constitutional risk factor for VTED.
Established risk factors, including deficiencies of protein C, protein S or antithrombin and the factor V Leiden and prothrombin mutation, are present in about one third of unselected patients with venous thromboembolism. In addition to these inherited thrombophilic defects, elevated plasma levels of factor VIIIc have been suggested to be important in the pathogenesis of (recurrent) venous thromboembolism. The objective of this study was to assess the relevance of factor VIIIc plasma concentration in consecutive patients with venous thromboembolism.
We studied the prevalence of elevated plasma levels of factor VIIIc in 65 patients with a proven single episode and in 60 matched patients with documented recurrent venous thromboembolism. The reference group consisted of 60 age- and sex-matched patients who were referred for suspected venous thromboembolism, which was refuted by objective testing and long-term clinical follow-up. To minimalize the influence of the acute phase, blood was obtained at least 6 months after the thromboembolic event and results were adjusted for fibrinogen and C-reactive protein. Factor VIIIc was re-determined several years after the first measurement in a subset of patients to evaluate the variability over time. To study a possible genetic cause, a family study was done.
In the control, single and recurrent episode group, the prevalences of plasma levels of factor VIIIc above 175 IU/dl (90th percentile of controls) were 10% (95% CI: 4 to 21%), 19% (95% CI: 10 to 30%) and 33% (95% CI: 22 to 47%), respectively. For each 10 IU/dl increment of factor VIIIc, the risk for a single and recurrent episode of venous thrombosis increased by 10% (95% CI: 0.9 to 21%) and 24% (95% CI: 11 to 38%), respectively. Both low and high plasma levels of factor VIIIc were consistent over time (R = 0.80, p = 0.01). A family study indicated a high concordance for elevated factor VIIIc plasma concentrations among first degree family members. Adjustment for fibrinogen, C-reactive protein and known thrombophilic risk factors did not change the observed association of elevated factor VIIIc with thrombosis.
Elevated plasma levels of factor VIIIc are a significant, prevalent, independent and dose-dependent risk factor for venous thromboembolism. It also predisposes to recurrent venous thromboembolism.
Elevated plasma levels of interleukin 8 (IL-8) were previously shown to be associated with recurrent venous thrombosis. To assess the risk of venous thrombosis, IL-8 plasma concentrations were measured in patients and control subjects of the Leiden Thrombophilia Study (LETS). This population based case-control study included 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. The risk of venous thrombosis for subjects with elevated IL-8 levels (above 90th percentile of controls) compared with subjects with IL-8 levels below the 90th percentile was increased 1.8-fold (95%CI 1.2-2.8). Adjusted for age and sex, the odds ratio was 1.9 (95%CI 1.3-2.8). IL-8 concentrations were weakly correlated with age, male sex, and concentrations of C-reactive protein, factor VIII coagulation activity and homocysteine, but adjustment for these factors did not substantially affect the association between IL-8 and venous thrombosis. Our results suggest that IL-8 is a risk factor for venous thrombosis.
Coffee is a major source of caffeine, which has been shown to acutely reduce sensitivity to insulin, but also has potentially beneficial effects. We prospectively investigated the association between coffee consumption and risk of clinical type 2 diabetes in a population-based cohort of 17111 Dutch men and women aged 30-60 years. During 125774 person years of follow-up, 306 new cases of type 2 diabetes were reported. After adjustment for potential confounders, individuals who drank at least seven cups of coffee a day were 0.50 (95% CI 0.35-0.72, p=0.0002) times as likely as those who drank two cups or fewer a day to develop type 2 diabetes. Coffee consumption was associated with a substantially lower risk of clinical type 2 diabetes.
Epidemiologic studies suggest that higher polyphenol intake from fruits and vegetables is associated with decreased risk for cardiovascular disease. The mechanisms explaining this observation remain unclear. This review summarizes data suggesting that flavonoids improve endothelial function and inhibit platelet aggregation in humans. The vascular endothelium is a critical regulator of vascular homeostasis, and endothelial dysfunction contributes to the pathogenesis and clinical expression of coronary artery disease. Platelet aggregation is a central mechanism in the pathogenesis of acute coronary syndromes, including myocardial infarction and unstable angina. For these reasons, the observed effects of flavonoids on endothelial and platelet function might explain, in part, the observed beneficial effects of flavonoids on cardiovascular disease risk.
Emerging epidemiological evidence suggests that higher coffee consumption may reduce the risk of type 2 diabetes.
To examine the association between habitual coffee consumption and risk of type 2 diabetes and related outcomes.
We searched MEDLINE through January 2005 and examined the reference lists of the retrieved articles. Because this review focuses on studies of habitual coffee consumption and risk of type 2 diabetes, we excluded studies of type 1 diabetes, animal studies, and studies of short-term exposure to coffee or caffeine, leaving 15 epidemiological studies (cohort or cross-sectional).
Information on study design, participant characteristics, measurement of coffee consumption and outcomes, adjustment for potential confounders, and estimates of associations was abstracted independently by 2 investigators.
We identified 9 cohort studies of coffee consumption and risk of type 2 diabetes, including 193 473 participants and 8394 incident cases of type 2 diabetes, and calculated summary relative risks (RRs) using a random-effects model. The RR of type 2 diabetes was 0.65 (95% confidence interval [CI], 0.54-0.78) for the highest (>or=6 or >or=7 cups per day) and 0.72 (95% CI, 0.62-0.83) for the second highest (4-6 cups per day) category of coffee consumption compared with the lowest consumption category (0 or <or=2 cups per day). These associations did not differ substantially by sex, obesity, or region (United States and Europe). In the cross-sectional studies conducted in northern Europe, southern Europe, and Japan, higher coffee consumption was consistently associated with a lower prevalence of newly detected hyperglycemia, particularly postprandial hyperglycemia.
This systematic review supports the hypothesis that habitual coffee consumption is associated with a substantially lower risk of type 2 diabetes. Longer-term intervention studies of coffee consumption and glucose metabolism are warranted to examine the mechanisms underlying the relationship between coffee consumption and type 2 diabetes.
Coffee is among the most commonly consumed beverages in The Netherlands. Caffeine can acutely lower insulin sensitivity, but it is not clear whether tolerance for this effect develops after long-term regular intake. Furthermore, it is plausible that the effects of coffee are different from those of caffeine. Coffee contains hundreds of substances and there are indications that certain components may partly counter-act the effect of caffeine or may have independent beneficial effects. Intake of the coffee components chlorogenic acid, quinides, lignans, and trigonelline improved glucose metabolism in animal studies. Habitual coffee consumption has been studied in relation to the risk of diabetes mellitus type 2 in 12 cohort studies in Europe, the USA, and Japan. Generally, high coffee consumption was associated with a substantially lower risk of type-2 diabetes. The findings were similar for caffeinated and decaffeinated coffee, suggesting that the non-caffeine components of coffee may be responsible. Identification of these coffee components may lead to the development or selection of coffee types with improved effects on health.
Epidemiological studies suggest that high polyphenols intake from diet is associated with reduced risk for cardiovascular diseases. Platelet aggregation is a crucial mechanism in the pathogenesis and clinical expression of coronary acute syndrome, and there is extensive evidence that antiplatelet therapy reduces cardiovascular disease risk. In this review, the available literature on the effect of polyphenols supplementation on platelet aggregation in humans or animal models has been critically analyzed, taking into consideration the different experimental protocols employed. In some studies, polyphenols supplementation did not show any effect on platelet aggregation. However, in the most of the studies, polyphenols supplementation, either as purified compounds or food extracts, showed some inhibitory effects, both in humans and in animal models. The extent of the inhibition varies in a wide range, depending on the experimental conditions used. The observed inhibitory effect of polyphenols on platelet aggregation might explain, at least in part, the epidemiological data on beneficial effect of dietary polyphenols on cardiovascular disease risk and suggests a role for polyphenols in helping to prevent cardiovascular diseases.
Thrombosis after travel: reply to a perspective
- Cannegieter
Cannegieter SC. Thrombosis after travel: reply to a perspective. PloS
Med 2009; http://www.plosmedicine.org/annotation/listThread.action;
jsessionid=6B1280AF0031B6ACEA6935E7C14D83E6?root=13223.
Statistical Methods in Cancer Research Lyon: International Agency for Research on Cancer, 1980: 350. 25 van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus
- Ne Breslow
- Ne Day
24 Breslow NE, Day NE. Statistical Methods in Cancer Research. Lyon:
International Agency for Research on Cancer, 1980: 350.
25 van Dam RM, Feskens EJ. Coffee consumption and risk of type 2
diabetes mellitus. Lancet 2002; 360: 1477–8.
Coffee consumption and risk of type 2 diabetes: a systematic review
- Rm Dam
- Fb Hu
Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005; 294: 97–104.