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Prevalence and variables associated with an abnormal ankle-brachial index among patients with human immunodeficiency virus/acquired immunodeficiency syndrome
Abstract
Trial registration:
ClinicalTrials.gov NCT02264509.
... This approach may lead to a better stratification of the atherothrombotic risk by identifying the patient with polyvascular atherosclerotic disease. [12][13][14] The finding that most sixmonth deaths were associated with an acute atherothrombotic event (i.e. coronary, cerebrovascular, or peripheral) reinforces the notion that a complete assessment of atherothrombosis risk is mandatory following an acute occlusive arterial event. ...
Objectives
The frequency and implications of peripheral artery disease (PAD) in some risk groups are not entirely characterized in Latin America. We studied PAD prevalence, risk factors, and six-month outcomes in stable outpatients with a history of a recent acute coronary syndrome (ACS), or at high coronary risk.
Methods
We recruited 830 outpatients in 43 Mexican sites (median age: 64.8 years; 57.8% men). Inclusion criteria were age >18 years, and ACS within 30 days, or age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors. Patients received standardized assessments at baseline and six-month follow-up for medical history, ankle-brachial index (ABI), and the Edinburgh Claudication Questionnaire (ECQ).
Results
ABI <0.8 was found in 10.5%, <0.9 in 22.5%, >1.3 in 4.8%, and >1.4 in 3.6%, without differences according to sex or selection criteria. Positive ECQ was found in 7.6%. ABI <0.9 was directly associated with age, diabetes, ACS, and chronic kidney disease, but inversely associated with BMI >27. The six-month case-fatality and atherothrombotic events rates were 1.6% and 3.6%, respectively. In patients with ABI <0.9 and ABI <0.8, the six-month case-fatality rates were 2.5% ( p = 0.27) and 5.4% ( p = 0.03), respectively. In a Cox proportional-hazards model, baseline factors associated with death were age ≥65, ABI <0.8, and ACS.
Conclusions
Subclinical PAD is more common than symptomatic claudication in high-risk coronary outpatients. Low ABI is associated with reduced short-term survival in patients with recent ACS or at high coronary risk.
Peripheral arterial disease (PAD) is a clinical manifestation of atherosclerosis and mainly refers to elderly patients, having a negative impact on their functionality and quality of life. The findings of previous studies in HIV-infected patients have shown that cardiovascular risk is higher and PAD occurs more frequently than in the general population. There are also contradictory observations. Much less is known about the ankle-brachial index (ABI) value in asymptomatic HIV-infected patients. The aim of this study was to evaluate the prevalence of PAD and ankle-brachial index abnormalities as well as to determine risk factors related to the disease in a group of Polish HIV-positive patients.
One hundred and eleven young to middle aged HIV-positive subjects and 40 noninfected subjects were enrolled into the study. Resting ABI measurements were performed and cardiovascular risk was analysed as well. Subgroups were created according to the ABI values: low (PAD), borderline, normal, high and altered ABI. Symptomatic PAD was observed in 2 HIV-positive patients, asymptomatic PAD was not diagnosed. The ABI value is lower and more varied, in 22.5% of the study group altered ABI values were found. Six subjects demonstrated borderline ABI, and 15 high ABI, including >1.4. In the control group no low or very high values were reported. A relation between low ABI and cardiovascular family history and between altered ABI and high-density-lipoprotein cholesterol (HDL-C) level was demonstrated.
In young and middle-aged HIV-positive patients, symptomatic PAD prevalence is comparable to that observed in the overall population. Among asymptomatic patients PAD is not reported. The ABI value in HIV-positive patients is more varied compared to the HIV-negative subjects; the altered ABI shows a strong relation with low HDL-C levels and metabolic syndrome.
The incidence of myocardial infarction (MI) is lower in France than in English-speaking and northern European countries. We estimated the incidence of MI in the HIV-infected population in France, on the basis of the data from the FHDH-ANRS CO4 cohort, by comparison with the general population. The sex- and age-standardized morbidity ratio was estimated as 1.5 [95% confidence interval (CI) 1.3-1.7] overall, 1.4 (95% CI 1.3-1.6) in men and 2.7 (95% CI 1.8-3.9) in women.
Patients infected with HIV have an increased risk for accelerated atherosclerosis. Elevated levels of osteoprotegerin, an inflammatory cytokine receptor, have been associated with a high incidence of cardiovascular disease (including peripheral arterial disease, or PAD), acute coronary syndrome, and cardiovascular mortality. The objective of this study was to determine whether PAD is prevalent in an HIV-infected population, and to identify an association with HIV-specific and traditional cardiovascular risk factors, as well as levels of osteoprotegerin.
One hundred and two patients infected with HIV were recruited in a cross-sectional study. To identify the prevalence of PAD, ankle-brachial indices (ABIs) were measured. Four standard ABI categories were utilized: < or = 0.90 (definite PAD); 0.91-0.99 (borderline); 1.00-1.30 (normal); and >1.30 (high). Medical history and laboratory measurements were obtained to determine possible risk factors associated with PAD in HIV-infected patients.
The prevalence of PAD (ABI < or = 0.90) in a young HIV-infected population (mean age: 48 years) was 11%. Traditional cardiovascular risk factors, including advanced age and previous cardiovascular history, as well as elevated C-reactive protein levels, were associated with PAD. Compared with patients with normal ABIs, patients with high ABIs had significantly elevated levels of osteoprotegerin [1428.9 (713.1) pg/ml vs. 3088.6 (3565.9) pg/ml, respectively, p = 0.03].
There is a high prevalence of PAD in young HIV-infected patients. A number of traditional cardiovascular risk factors and increased osteoprotegerin concentrations are associated with abnormal ABIs. Thus, early screening and aggressive medical management for PAD may be warranted in HIV-infected patients.
In spite of recent advances in treatment and care available in most developed countries, the HIV/AIDS pandemic continues to spread throughout the developing world.
Structural inequalities continue to fuel the epidemic in all societies, and HIV infection has increasingly been concentrated in the poorest, most marginalized sectors of society in all countries. The relationship between HIV/AIDS and social and economic development has therefore become a central point in policy discussions about the most effective responses to the epidemic.
Important progress has been made in recent United Nations initiatives. Maintaining long-term commitment to initiatives such as the Global Fund to Fight AIDS, Tuberculosis and Malaria is especially important in the wake of September 11 and ensuing events, which threaten to redirect necessary resources to seemingly more urgent security concerns.
Several lines of evidence point to kidney disease as an important complication of human immunodeficiency virus (HIV) infection. Kidney function is abnormal in up to 30% of HIV-infected patients, AIDS-related kidney disease has become a relatively common cause of end-stage renal disease ( ESRD) requiring dialysis, and kidney disease may be associated with progression to AIDS and death [1-4]. Because HIV caregivers commonly manage all aspects of treatment for their patients, these clinicians are in the unique and important position to identify those patients at risk for renal disease and implement potentially preventative and therapeutic strategies. Consequently, an understanding of the causes, epidemiology, screening methods, and thermerular filtration rate [GFR]) (C-III); a renal function estimate also allows the caregiver to properly prescribe those antiretrovirals and other commonly used medications that require renal adjustment. If there is no evidence of proteinuria at initial evaluation, patients at high risk for the development of proteinuric renal disease ( e. g., African American persons, those with CD4(+) cell counts <200 cells/mu L or HIV RNA levels >4000 copies/mL, or those with diabetes mellitus, hypertension, or hepatitis C virus coinfection) should undergo annual screening (B-II). Patients with proteinuria of grade >= 1 + by dipstick analysis or reduced renal function (GFR, <60 mL/min per 1.73 m(2)) should be referred to a nephrologist and undergo additional evaluation, including quantification of proteinuria, renal ultrasound, and potentially renal biopsy (B-II). Therapy for HIV-associated renal diseases should be individualized to the patient's clinical circumstances and to the underlying renal histology findings. Blood pressure should be controlled, with the initial preferential use of angiotensin-converting enzyme ( ACE) inhibitors or angiotensin receptor blockers for those patients with proteinuria (B-II); however, calcium channel blockers should be avoided in treating patients receiving protease inhibitors (D-II). Patients with HIV-associated nephropathy (HIVAN) should be treated with HAART at diagnosis (B-II). HAART should not be withheld from patients simply because of the severity of their renal dysfunction (B-III). Addition of ACE inhibitors or angiotensin receptor blockers (ARBs) should be considered in treating both adult and pediatric patients with HIVAN if HAART alone does not result in improvement of renal function (B-II). Prednisone should also be considered in treating adult patients with refractory HIVAN (B-II), although steroids are not recommended for children with HIVAN (D-II). Preliminary data suggest that renal transplantation may be a viable treatment option for patients with ESRD and should be considered if provided in a supervised clinical trial or at centers with adequate experience in this area (C-III). Dialysis and the placement of arteriovenous fistulae should not be withheld for patients solely because of HIV infection (A-II). Among those patients at higher risk (see "Renal Effects of Commonly Used Medications in HIV Care"), biannual monitoring for renal function and urinary abnormalities is warranted for those receiving indinavir (B-II) or tenofovir (B-III). HIV-infected patients requiring hemodialysis should have antibody to hepatitis B surface antigen (anti-HBs) titers checked after receiving a standard primary series of 3 hepatitis B vaccinations, and they should receive a fourth injection if these levels are ! 10 IU/L (B-II).
The worldwide epidemic of HIV continues to expand in many regions of the world, particularly in southern Africa, South and Southeast Asia, East Asia and Eastern Europe and Central Asia. Estimates are that at the end of 2005 there were 38.6 million persons living with HIV infection and that 4.1 million new infections and 2.8 million deaths from HIV occurred during the year. Regionally different patterns predominate from generalized heterosexual epidemics in sub-Saharan Africa and parts of the Caribbean to mixes of epidemics in which transmission among injection drug users, their sexual partners, commercial sex workers and their partners intersect. Multilateral and bilateral antiretroviral access campaigns, such as the World Health Organization's 3 x 5 initiative, have resulted in broader access to live-saving therapy for infected persons in low- and middle-income countries, but several million infected people who are clinically eligible for antiretroviral therapy remain untreated. The public health challenge worldwide is to keep the uninfected and to treat and care for those who have already been infected.
Atherosclerosis has been assessed in human immunodeficiency virus (HIV)-infected persons by using various methods. Peripheral arterial disease (PAD) has not been evaluated, however. We studied the cross-sectional prevalence of lower limb PAD in an HIV-infected population.
PAD was assessed using the Edinburgh Claudication Questionnaire and by measuring the systolic ankle-brachial blood pressure index (ABI) at rest and after exercise. Patients with PAD were further evaluated by duplex scan of lower limb arteries.
Ninety-two consecutive HIV-infected patients were evaluated (23.9% women; mean age, 49.5 years; 61.9% current smokers). Claudication was reported by 15.2% of the patients. PAD was found in 20.7% of the patients: 9.8% had an abnormal ABI (<0.90) at rest, and 10.9% had normal ABI at rest but a >25% decrease after exercise. Of the patients with PAD, 84.2% were investigated with duplex scan, all of whom had atherosclerotic occlusions or stenoses of the iliac or femoral arteries. Age, diabetes, smoking, and low CD4+ T lymphocyte counts were identified as independent predictors of PAD.
The prevalence of symptomatic and asymptomatic PAD is high in the HIV-infected population and is much higher than expected (prevalence in the general population, approximately 3% at 60 years). This study suggests the presence of an epidemic of PAD approximately 20 years earlier in the HIV-infected than in the general population. Larger epidemiological studies are needed to better define risk factors and to evaluate whether PAD is associated with increased mortality, as it is in the general population.
HIV-infected patients are living longer, with successful antiretroviral therapy. However, recent reports suggest increased cardiovascular disease (CVD) rates among HIV-infected patients (1), and cardiovascular disease has become an important cause of morbidity and mortality in this population (2). Increased CVD rates may be related to traditional risk factors, including aging of the population, higher smoking rates, dyslipidemia, insulin resistance and impaired glucose tolerance, and changes in body composition, with relative accumulation of central fat in some patients. As well, CVD may be due to non-traditional factors, including inflammation, and direct effects of the virus on the vasculature, as well as from direct effects of specific antiretroviral drugs. Significant questions remain as to the pathogenesis, detection, and treatment of coronary heart disease (CHD) and related risk factors in HIV-infected patients. These controversies include, among others, the design of adequate trials to determine disease incidence, and the utility of existing CHD guidelines for screening, treatment, and risk stratification.
To ascertain the state of the science with respect to these and related questions, a multidisciplinary conference with interested HIV specialists, cardiologists, endocrinologists, and primary care physicians, NIH representatives, and patient advocates was convened June 28th–30th in Chicago chaired by Drs. Steven Grinspoon and Robert Eckel. The discussions focused on 6 areas of interest, including: 1) Contribution of Metabolic and Anthropometric Abnormalities to CHD Risk Factors (Chairs C Grunfeld and D Kotler), 2) Epidemiological Evidence for CHD and Relationship to HAART (Chairs J Curier and J Lundgren), 3) Effects of HIV Infection and Antiretroviral Therapy on the Heart and Vasculature (Chairs M Dube and S Lipshultz), 4) Screening and Assessment of CHD in the HIV Population (Chairs P Hsue and K Squires), 5) Development of Appropriate Risk Prediction Models in HIV-infected Patients (Chairs M Schambelan, K Yarasheski, P Wilson), and 6) Prevention Strategies for CHD in HIV-infected Speakers (Chairs J Stein and C Hadigan). For each area of interest, specific topics were covered in plenary lectures and in subsequent discussions with conference participants. Summaries for each group were reported out to the conference participants for discussion, and submitted for publication (See Circulation on line for individual group summaries and list of writing group members). The proceedings were sponsored by an unrestricted educational grant from Bristol Meyers Squibb to the American Heart Association, and also by the American Academy of HIV Medicine. Per AHA guidelines, the sponsor had no role in the planning of the meeting, choice of speakers, speaker content, or formulation of the scientific summary.
Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function and structure can be used to study the pathogenesis and progression of CVD, including the effects of ART and other interventions. The objective of this report is to understand methods to assess vascular (dys)function and report our experience in the Arterial Elasticity Substudy in the Strategic Timing of AntiRetroviral Treatment (START) trial.
We review literature and analyze baseline data from the Arterial Elasticity Substudy, which estimated vascular (dys)function through analysis of the diastolic blood pressure (BP) waveform. Linear regression was used to study cross-sectional associations between baseline clinical factors and small or large arterial elasticity.
Arterial elasticity measurement was chosen for its improved measurement reproducibility over other methodologies and the potential of small arterial elasticity to predict clinical risk. Analysis of baseline data demonstrates that small artery elasticity is impaired (lower) with older age and differs by race and between geographical regions. No HIV-specific factors studied remained significantly associated with arterial elasticity in multivariate models.
Longitudinal analyses in this substudy will provide essential randomized data with which to study the effects of early ART initiation on the progression of vascular disease among a diverse global population. When combined with future biomarker analyses and clinical outcomes in START, these findings will expand our understanding of the pathogenesis of HIV-related CVD.
© 2015 British HIV Association.
The clinical challenges confronting patients with human immunodeficiency virus (HIV) have shifted from acquired immunodeficiency syndrome (AIDS)-related illnesses to chronic diseases, such as coronary artery disease, chronic lung disease, and chronic anemia. With the growing burden of HIV-related heart, lung, and blood (HLB) disease, the National Heart, Lung, and Blood Institute (NHLBI) recognizes it must stimulate and support HIV-related HLB research. Because HIV offers a natural, accelerated model of common pathological processes, such as inflammation, HIV-related HLB research may yield important breakthroughs for all patients with HLB disease. This paper summarizes the cardiovascular recommendations of an NHLBI Working Group, Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases, charged with identifying scientific priorities in HIV-related HLB disease and developing recommendations to promote multidisciplinary collaboration among HIV and HLB investigators. The working group included multidisciplinary sessions, as well as HLB breakout sessions for discussion of disease-specific issues, with common themes about scientific priorities and strategies to stimulate HLB research emerging in all 3 groups.
Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Background:
Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally.
Methods:
We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0·90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC).
Findings:
34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112,027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45-49 years was 5·28% (95% CI 3·38-8·17%) in women and 5·41% (3·41-8·49%) in men, and at age 85-89 years, it was 18·38% (11·16-28·76%) in women and 18·83% (12·03-28·25%) in men. Prevalence in men was lower in LMIC than in HIC (2·89% [2·04-4·07%] at 45-49 years and 14·94% [9·58-22·56%] at 85-89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6·31% [4·86-8·15%] of women aged 45-49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2·72 (95% CI 2·39-3·09) in HIC and 1·42 (1·25-1·62) in LMIC, followed by diabetes (1·88 [1·66-2·14] vs 1·47 [1·29-1·68]), hypertension (1·55 [1·42-1·71] vs 1·36 [1·24-1·50]), and hypercholesterolaemia (1·19 [1·07-1·33] vs 1·14 [1·03-1·25]). Globally, 202 million people were living with peripheral artery disease in 2010, 69·7% of them in LMIC, including 54·8 million in southeast Asia and 45·9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28·7% in LMIC and 13·1% in HIC.
Interpretation:
In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease.
Funding:
Peripheral Arterial Disease Research Coalition (Europe).
Introduction:
Human immunodeficiency virus (HIV) infection has been associated with a higher risk of subclinical atherosclerosis and cardiovascular events. Peripheral arterial disease (PAD) is a good marker of systemic atherosclerosis and a powerful predictor of cardiovascular morbidity and mortality. The objective of this study was to determine the prevalence of asymptomatic PAD and associated risk factors in HIV-infected people.
Methods:
Cross-sectional study was conducted on all consecutive HIV-positive patients older than 20 years without symptoms of intermittent claudication who attended our clinic between November 2008 and December 2009. PAD was assessed by measuring the ankle-brachial index (ABI) at rest. To define PAD, an ABI ≤ 0.90 was used. Main epidemiological and clinical characteristics of the HIV infection and cardiovascular risk factors (CVRF) were recorded.
Results:
Two hundred and five patients were evaluated (66.8% male), with a mean age of 41 years and there was a median of 2 CVRF (63.9% smokers). Prevalence of asymptomatic PAD (ABI ≤ 0.90) was 6.3% (n=13). There was only 1 patient with a high ABI (>1.40). In the multivariate analysis, factors significantly associated with PAD were overweight (adjusted odds ratio [ORadj] 4.21; 95% confidence interval [CI] 1.00-18.78), obesity (ORadj 5.76; 95% CI 1.17-28.37) and clinical stage C of HIV infection (ORadj 2.95; 95% CI 1.00-9.83).
Conclusions:
Prevalence of asymptomatic PAD in a relatively young HIV-infected cohort is similar to that observed in the uninfected middle-aged adult population. Overweight, obesity and advanced clinical stage of HIV infection (AIDS-defining conditions) were identified as independent risk factors for PAD.
Cardiovascular disease, and particularly coronary heart disease, is an emerging area of concern in the HIV population. Since the advent of efficient antiretroviral therapies and the consequent longer patient life span, an increased risk for myocardial infarction has been observed in HIV-infected patients compared with the general population in Western countries. The pathophysiology of this accelerated atherosclerotic process is complex and multifactorial. Traditional cardiovascular risk factors-overrepresented in the HIV population-associated with uncontrolled viral replication and exposure to antiretroviral drugs (per se or through lipid and glucose disturbances) could promote acute ischemic events. Thus, despite successful antiviral therapy, numerous studies suggest a role of chronic inflammation, together with immune activation, that could lead to vascular dysfunction and atherothrombosis. It is time for physicians to prevent coronary heart disease in this high-risk population through the use of tools employed in the general population. Moreover, the lower median age at which acute coronary syndromes occur in HIV-infected patients should shift prevention to include patients <45 years of age. Available cardiovascular risk scores in the general population usually fail to screen young patients at risk for myocardial infarction. Moreover, the novel vascular risk factors identified in HIV-related atherosclerosis, such as chronic inflammation, immune activation, and some antiretroviral agents, are not taken into account in the available risk scores, leading to underestimation of cardiovascular risk in the HIV population. Cardiovascular prevention in HIV-infected patients is a challenge for both cardiologists and physicians involved in HIV care. We require new tools to assess this higher risk and studies to determine whether intensive primary prevention is warranted.
Background: Cardiovascular disease (CVD) is an increasing cause of morbidity and mortality in HIV-infected patients. However, it is controversial whether HIV infection contributes to accelerated atherosclerosis independent of traditional CVD risk factors.
Methods: Cross-sectional study of HIV-infected participants and controls without pre-existing CVD from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) and the Multi-Ethnic Study of Atherosclerosis (MESA). Preclinical atherosclerosis was assessed by carotid intima-medial thickness (cIMT) measurements in the internal/bulb and common regions in HIV-infected participants and controls after adjusting for traditional CVD risk factors.
Results: For internal carotid, mean IMT was 1.17 ± 0.50 mm for HIV-infected participants and 1.06 ± 0.58 mm for controls (P < 0.0001). After multivariable adjustment for demographic characteristics, the mean difference of HIV-infected participants vs. controls was 0.188 mm [95% confidence interval (CI) 0.113-0.263, P < 0.0001]. Further adjustment for traditional CVD risk factors modestly attenuated the HIV association (0.148 mm, 95% CI 0.072-0.224, P = 0.0001). For the common carotid, HIV infection was independently associated with greater IMT (0.033 mm, 95% CI 0.010-0.056, P = 0.005). The association of HIV infection with IMT was similar to that of smoking, which was also associated with greater IMT (internal 0.173 mm, common 0.020 mm).
Conclusion: Even after adjustment for traditional CVD risk factors, HIV infection was accompanied by more extensive atherosclerosis measured by IMT. The stronger association of HIV infection with IMT in the internal/bulb region compared with the common carotid may explain previous discrepancies in the literature. The association of HIV infection with IMT was similar to that of traditional CVD risk factors, such as smoking.
Human immunodeficiency virus (HIV) infection has been associated with a higher risk of subclinical atherosclerosis and cardiovascular events. Peripheral arterial disease (PAD) is a good marker of systemic atherosclerosis and a powerful predictor of cardiovascular morbidity and mortality. The objective of this study was to determine the prevalence of asymptomatic PAD and associated risk factors in HIV-infected people.
Cross-sectional study was conducted on all consecutive HIV-positive patients older than 20 years without symptoms of intermittent claudication who attended our clinic between November 2008 and December 2009. PAD was assessed by measuring the ankle-brachial index (ABI) at rest. To define PAD, an ABI ≤ 0.90 was used. Main epidemiological and clinical characteristics of the HIV infection and cardiovascular risk factors (CVRF) were recorded.
Two hundred and five patients were evaluated (66.8% male), with a mean age of 41 years and there was a median of 2 CVRF (63.9% smokers). Prevalence of asymptomatic PAD (ABI ≤ 0.90) was 6.3% (n=13). There was only 1 patient with a high ABI (>1.40). In the multivariate analysis, factors significantly associated with PAD were overweight (adjusted odds ratio [ORadj] 4.21; 95% confidence interval [CI] 1.00-18.78), obesity (ORadj 5.76; 95% CI 1.17-28.37) and clinical stage C of HIV infection (ORadj 2.95; 95% CI 1.00-9.83).
Prevalence of asymptomatic PAD in a relatively young HIV-infected cohort is similar to that observed in the uninfected middle-aged adult population. Overweight, obesity and advanced clinical stage of HIV infection (AIDS-defining conditions) were identified as independent risk factors for PAD.
The multicenter national Mortalité 2005 survey aimed at describing the distribution of causes of death among HIV-infected adults in France in 2005 and its changes as compared with 2000.
Physicians involved in the management of HIV infection notified deaths and documented the causes using a standardized questionnaire similar to the previous survey performed in 2000.
Overall, 1042 deaths were notified in 2005 (vs 964 in 2000): with median age, 46 years (vs 41 years); men, 76%; and median last CD4 cell count, 161/mm (vs 94). The proportion of underlying causes of death due to AIDS decreased (36% in 2005 vs 47% in 2000), and the proportion of cancer not related to AIDS or hepatitis (17% vs 11%), liver related disease (15% vs 13%: hepatitis C, 11%, and hepatitis B, 2%), cardiovascular disease (8% vs 7%), or suicide (5% vs 4%) increased. Among the 375 AIDS-related deaths, the most frequent event was non-Hodgkin lymphoma (28%). Among cancers not related to AIDS or hepatitis, the most frequent localizations were lung (31%) and digestive tract (14%). Among the 154 liver-related deaths, 24% were due to hepatocarcinoma.
The heterogeneity of causes of death among HIV-infected adults was confirmed and intensified in 2005, with 3 causes following AIDS: cancers and liver-related and cardiovascular diseases.
Excess mortality has decreased among human immunodeficiency virus (HIV)-infected patients but without evidence of a decrease among patients with AIDS. We assessed temporal changes in excess mortality and elucidated risk factors for excess mortality in patients with AIDS diagnosed in the era of highly active antiretroviral therapy (HAART).
We included 1188 patients of the Longitudinal Study of Ocular Complications in AIDS who were aged 25-64 years at enrollment and who received a diagnosis of AIDS after 1995. We calculated excess mortality as the age-, year-, and sex-adjusted difference in mortality rates between patients with AIDS and persons in the US general population during the period 1999-2007. We used a relative survival model to identify risk factors for excess mortality.
There were a mean of 50 excess deaths per 1000 person-years (95% confidence interval [CI], 44-57 excess deaths per 1000 person-years) during 1999-2007. Excess mortality almost halved, with an annual decrease of 8.0% per year (95% CI, 3.0%-12.7%; P = .002) but remained high at 36 excess deaths per 1000 person-years in 2007. Viral load >400 copies/mL (compared with <or= 400 copies/mL; risk ratio, 3.4; 95% CI, 2.3-5.0), CD4(+) count <200 cells/μL (compared with >or= 200 cells/μL; risk ratio, 2.7; 95% CI, 1.9-3.9), and cytomegalovirus retinitis (risk ratio, 1.6; 95% CI, 1.2-2.1) were the strongest risk factors for excess mortality.
Excess mortality among patients with AIDS was nearly halved in the HAART era and most strongly linked to stage of HIV disease. These results reflect the continuing improvements in AIDS management but also highlight that excess mortality remains ∼5 times higher in patients with AIDS than in HIV-infected patients without AIDS.
Indications Although other methods exist to assess the peripheral vasculature more objectively, the ankle-brachial index represents a simple, reliable method for diagnosing pe- ripheral arterial disease. More specific indications include evaluation of leg pain, evaluation for ischemia of the legs (symptoms of claudication, pain at rest, and the presence of foot ulcers or gangrene), screening for atherosclerosis, and evaluation of vascular compromise in patients with trauma of the lower legs. 3 Measurement of the ankle-brachial index may also be useful in determining the prognosis for patients with diffuse vascular disease and for evaluating the success of interventional or surgical procedures, such as angioplasty, stenting, or lower-extremity bypass surgery. Contraindications The few contraindications for the measurement of the ankle-brachial index include excruciating pain in the patient's legs or feet and the presence of deep venous thrombosis, which could lead to thrombus dislodgment. In a patient with suspect - ed deep venous thrombosis, it would be prudent to perform a duplex ultrasound study to exclude this possibility before measuring the ankle-brachial index. Al- though the readings may be altered when vessels are calcified or incompressible (such as in elderly patients, patients with diabetes, or patients with end-stage renal failure requiring dialysis), these conditions are not absolute contraindications to measuring the ankle-brachial index.
Since it was first recognized clinically in 1981, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has gone from a fatal syndrome to a chronic disease in persons receiving highly active antiretroviral therapy (HAART). Although the first antiretroviral agent, zidovudine (
Fourteen cases of vasculitis associated with human immunodeficiency virus infection have thus far been described. Five of these cases may be classified as angiocentric immunoproliferative disorders, including benign lymphocytic angiitis, lymphomatoid granulomatosis, and angiocentric lymphoma. We report a case of benign lymphocytic angiitis of T cell lineage. Extensive studies found no evidence of viral antigens in the inflammatory infiltrates, and immunologic evaluation of the pathologic lesions revealed the infiltrating cells to be predominantly CD3+, CD8+, CD4-. A significant number of these lymphocytes demonstrated a deletion of T cell antigen receptor determinants. We believe that in certain cases of human immunodeficiency virus disease, there occurs a spectrum of lymphoproliferative disorders with angiocentric features that lead to the clinical picture of systemic necrotizing vasculitis. Clinicians should be aware of this association.
Arterial aneurysms have only recently been associated with the human immunodeficiency virus (HIV). The clinical and pathological features of 10 HIV-positive patients with arterial aneurysms were retrospectively evaluated. These aneurysms were unusual in that they affected young black patients, occurred in atypical sites, and tended toward multiplicity. Surgery was performed in eight patients. Acute and chronic inflammatory changes were revealed by means of histologic examination of the aneurysm walls, with occlusion of the vasa vasora by inflammatory infiltrate or edema being a prominent feature. Culture of the aneurysm wall or thrombus yielded positive results in two patients. The association between HIV and aneurysms may be coincidental, caused by direct viral action or by bacterial infection resulting from immunosuppression. Implications for therapy are discussed, and the need for further study is highlighted.
to preliminarily describe the clinical features and management of arterial occlusive disease in human immunodeficiency virus (HIV) infected patients.
twenty HIV positive patients with symptomatic large-vessel arterial occlusion treated by a tertiary vascular unit in a 3-year period.
retrospective review of clinical case records.
patients were noted to be young (median age 37 years), with preponderance of males. Twelve patients had evidence of advanced HIV infection. All patients had critical ischaemia, involving the upper limbs in four and the lower limbs in 16. Coagulation abnormalities were noted in two cases. Operative intervention in 18 patients included revascularisation in seven. Thrombotic occlusion of normal-looking arteries was noted. Arterial biopsy revealed leucoIcytoclastic vasculitis indicative of HIV arteritis in three of five cases examined.
initial experience with large-vessel occlusive disease in HIV positive patients suggests an underlying arteritic aetiology, with clinical and pathological features distinct from atherosclerosis. Further in-depth study is necessary to clarify the pathophysiological basis thereof.
Reviews and studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of HIV infection in relation to cardiac illness in both children and adults. The introduction of HAART regimens has significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected people expected. However, early data raised concerns about HAART being associated with an increase in both peripheral and coronary arterial diseases. In this review we discuss HIV-associated cardiovascular complications focusing on pathogenetic mechanisms that could have a role in diagnosis, management, and therapy of these complications in the HAART era.
To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies.
Baseline data from 17,852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999.
Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy.
Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (> or = 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level.
HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.
The distribution of risk factors for cardiovascular disease in patients aged 35–44 years who were treated for human immunodeficiency
virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease
inhibitor-containing regimen (n = 223), compared with HIV-1-uninfected men (n = 527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level,
a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was
found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed
among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR],
1.20) and women (RR, 1.59; P < 10-6 for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for
HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy,
risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered
for all patients who have them.
AIDS-related death and disease rates have declined in the highly active antiretroviral therapy (HAART) era and remain low; however, current causes of death in HAART-treated patients remain ill defined.
To describe mortality trends and causes of death among HIV-infected patients in the HAART era.
Prospective, multicenter, observational cohort study of participants in the HIV Outpatient Study who were treated from January 1996 through December 2004.
Rates of death, opportunistic disease, and other non-AIDS-defining illnesses (NADIs) determined to be primary or secondary causes of death.
Among 6945 HIV-infected patients followed for a median of 39.2 months, death rates fell from 7.0 deaths/100 person-years of observation in 1996 to 1.3 deaths/100 person-years in 2004 (P=0.008 for trend). Deaths that included AIDS-related causes decreased from 3.79/100 person-years in 1996 to 0.32/100 person-years in 2004 (P=0.008). Proportional increases in deaths involving liver disease, bacteremia/sepsis, gastrointestinal disease, non-AIDS malignancies, and renal disease also occurred (P=or<0.001, 0.017, 0.006, <0.001, and 0.037, respectively.) Hepatic disease was the only reported cause of death for which absolute rates increased over time, albeit not significantly, from 0.09/100 person-years in 1996 to 0.16/100 person-years in 2004 (P=0.10). The percentage of deaths due exclusively to NADI rose from 13.1% in 1996 to 42.5% in 2004 (P<0.001 for trend), the most frequent of which were cardiovascular, hepatic, and pulmonary disease, and non-AIDS malignancies in 2004. Mean CD4 cell counts closest to death (n=486 deaths) increased from 59 cells/microL in 1996 to 287 cells/microL in 2004 (P<0.001 for trend). Patients dying of NADI causes were more HAART experienced and initiated HAART at higher CD4 cell counts than those who died with AIDS (34.5% vs 16.8%, respectively, received HAART for 4 of more years, P<0.0001; 22.4% vs 7.8%, respectively, initiated HAART with CD4 cell counts of more than 350 cells/microL, P<0.001).
Although overall death rates remained low through 2004, the proportion of deaths attributable to non-AIDS diseases increased and prominently included hepatic, cardiovascular, and pulmonary diseases, as well as non-AIDS malignancies. Longer time spent receiving HAART and higher CD4 cell counts at HAART initiation were associated with death from non-AIDS causes. CD4 cell count at time of death increased over time.
Metabolic changes and smoking are common among HIV patients and may confer increased cardiovascular risk.
The aim of the study was to determine acute myocardial infarction (AMI) rates and cardiovascular risk factors in HIV compared with non-HIV patients in two tertiary care hospitals.
We conducted a health care system-based cohort study using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients. AMI rates were determined among patients receiving longitudinal care between October 1, 1996, and June 30, 2004.
The primary outcome was myocardial infarction, identified by International Classification of Diseases coding criteria.
AMI was identified in 189 HIV and 26,142 non-HIV patients. AMI rates per 1000 person-years were increased in HIV vs. non-HIV patients [11.13 (95% confidence interval [CI] 9.58-12.68) vs. 6.98 (95% CI 6.89-7.06)]. The HIV cohort had significantly higher proportions of hypertension (21.2 vs. 15.9%), diabetes (11.5 vs. 6.6%), and dyslipidemia (23.3 vs. 17.6%) than the non-HIV cohort (P < 0.0001 for each comparison). The difference in AMI rates between HIV and non-HIV patients was significant, with a relative risk (RR) of 1.75 (95% CI 1.51-2.02; P < 0.0001), adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. In gender-stratified models, the unadjusted AMI rates per 1000 person-years were higher for HIV patients among women (12.71 vs. 4.88 for HIV compared with non-HIV women), but not among men (10.48 vs. 11.44 for HIV compared with non-HIV men). The RRs (for HIV vs. non-HIV) were 2.98 (95% CI 2.33-3.75; P < 0.0001) for women and 1.40 (95% CI 1.16-1.67; P = 0.0003) for men, adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. A limitation of this database is that it contains incomplete data on smoking. Smoking could not be included in the overall regression model, and some of the increased risk may be accounted for by differences in smoking rates.
AMI rates and cardiovascular risk factors were increased in HIV compared with non-HIV patients, particularly among women. Cardiac risk modification strategies are important for the long-term care of HIV patients.
To determine the outcome of surgical intervention in patients with HIV associated vascular disease.
Prospective clinical survey.
Routine voluntary testing for HIV/AIDS was performed in patients who presented to our unit with peripheral vascular disease. One hundred and nine patients (5.7%) were prospectively identified over a 5-year period (2001-2006).
24 patients presented with aneurysmal disease whilst occlusive disease was present in 66 patients. There was not much difference between patients with aneurysmal disease and patients with occlusive disease as to age, CD4 count and other risk factors for vascular disease. The peri-operative mortality for aneurysmal disease was 10.6% versus 3.6% for occlusive disease (p=0.264). Long-term mortality was significantly worse (p=0.049) for patients with aneurysmal disease. The results of revascularization in occlusive disease were poor with a limb salvage rate of 31.6%. There was no significant difference in CD4 T-cell counts between primary amputation and revascularization groups (p=0.058).
Patients with aneurysmal disease have a high peri-operative and long-term mortality and it appears that surgical intervention should be reserved for life-threatening aneurysms only. Patients with occlusive disease have a better survival rate but limb salvage is poor. Primary amputation may be preferable to bypass surgery in patients with critical limb ischaemia.
Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population.
1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults
Swiss HIV Cohort Study. High prevalence of peripheral arterial disease in HIV-infected persons
- D Periard
- M Cavassini
- P Taffé
- Swiss Hiv Cohort
- Study
Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study
- F J Palella
- Baker
- Rk
- A C Moorman
- Friis-Møller N
- Nair R
Ocular Complications of AIDS Research Group. Excess mortality in patients with AIDS in the era of highly active antiretroviral therapy: temporal changes and risk factors
- M A Puhan
- Van Natta
- Ml
- F J Palella
Occlusive arterial disease in HIV-infected patients: a preliminary report
- R Nair
- Robbs
- Jv
- R Chetty