Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study.

BACKGROUND: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. METHODS AND RESULTS: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). CONCLUSIONS: Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.

Prehypertension, hypertension, and the risk of acute myocardial infarction in HIV-infected and -uninfected veterans.

BACKGROUND: Compared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status. METHODS: The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression. RESULTS: Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07-2.39]; HR, 1.81 [95% CI, 1.22-2.68]; HR, 2.57 [95% CI, 1.76-3.76]; and HR, 2.76 [95% CI, 1.90-4.02], respectively). CONCLUSIONS: HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk.

HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation.

BACKGROUND: Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). METHODS: Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. RESULTS: HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64-4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions. CONCLUSIONS: These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.

Food insecurity is associated with poor virologic response among HIV-infected patients receiving antiretroviral medications.

BACKGROUND AND OBJECTIVE: Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications. DESIGN: This is a cross-sectional study. PARTICIPANTS AND SETTING: Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002-2008 who were receiving antiretroviral medications. MAIN MEASUREMENTS: Participants reporting "concern about having enough food for you or your family in the past 30 days" were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (<200 cells/µL) and unsuppressed HIV-1 RNA (>500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations. KEY RESULTS: Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts. CONCLUSIONS: Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.

The association between the receipt of lipid lowering therapy and HIV status among veterans who met NCEP/ATP III criteria for the receipt of lipid lowering medication.

OBJECTIVE: To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association. PARTICIPANTS AND DESIGN: A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection. MEASUREMENTS: Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome. RESULTS: The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively, p < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28-0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41-0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13-0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy. CONCLUSIONS: Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals.

The effect of lean fish consumption on triglyceride levels.

Marine omega-3 fatty acids have an important role in reducing the risk of coronary artery disease (CAD). The American Heart Association recommends 1 g/day of omega-3 fatty acids for patients with CAD, and for those without CAD, the consumption of a variety of fish (preferably fatty fish) at least twice a week is recommended. Greater amounts of omega-3 fatty acids (4 g per day) are recommended to treat hypertriglyceridemia. Fish oil capsules are often needed to provide the greater quantities of omega-3 fatty acids necessary to treat hypertriglyceridemia, which should not obscure the important triglyceride-lowering effects of seafood consumption. The effects of fish consumption on plasma lipids and lipoproteins are well described in studies that have generally been conducted with fatty fish and fish oil capsules. This study of a group of men and women in a strictly controlled dietary setting showed that compared with a cholesterol-free diet, both lean fish and beef diets raised plasma low-density lipoprotein cholesterol levels, but the fish diet resulted in lower levels of plasma total cholesterol, very-low-density lipoprotein (VLDL) triglycerides, and VLDL cholesterol, while the beef diet resulted in higher plasma high-density lipoprotein cholesterol levels. These findings can help practitioners to extend their dietary recommendations to incorporate significant quantities of low-fat fish to reduce triglyceride levels.

Comparative Effectiveness of Diabetic Oral Medications Among HIV-Infected and HIV-Uninfected Veterans.

OBJECTIVE: Type 2 diabetes is increasingly common in HIV-infected individuals. The objective of this study was to compare the glycemic effectiveness of oral diabetic medications among patients with and without HIV infection. RESEARCH DESIGN AND METHODS: A longitudinal cohort study was conducted among HIV-infected and uninfected veterans with type 2 diabetes initiating diabetic medications between 1999 and 2010. Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after medication initiation, adjusting for baseline HbA1c level and clinical covariates. A subanalysis using propensity scores was conducted to account for confounding by indication. RESULTS: A total of 2,454 HIV-infected patients and 8,892 HIV-uninfected patients initiated diabetic medications during the study period. The most commonly prescribed medication was metformin (n = 5,647, 50%), followed by a sulfonylurea (n = 5,554, 49%) and a thiazolidinedione (n = 145, 1%). After adjustment for potential confounders, there was no significant difference in the change in HbA1c level among the three groups of new users. HIV infection was not significantly associated with glycemic response (P = 0.24). Black and Hispanic patients had a poorer response to therapy compared with white patients, with a relative increase in HbA1c level of 0.16% (95% CI 0.08, 0.24) [1.7 mmol/mol (0.9, 2.6)] (P < 0.001) and 0.25% (0.11, 0.39) [2.7 mmol/mol (1.2, 4.3)] (P = 0.001), respectively. CONCLUSIONS: We found that glycemic response was independent of the initial class of diabetic medication prescribed among HIV-uninfected and HIV-infected adults with type 2 diabetes. The mechanisms leading to poorer response among black and Hispanic patients, who make up a substantial proportion of those with HIV infection and type 2 diabetes, require further investigation.

Association of comorbidity with physical disability in older HIV-infected adults.

Comorbidity, aging, and their impact on physical functioning will play an increasingly greater role in HIV medical care as the number of infected adults over 50 years of age grows. The study objective was to investigate the relationship of comorbidity and age with physical functioning in HIV-infected and HIV-negative patients. Eight hundred eighty-nine HIV-infected veterans and 647 HIV-negative veterans from the Veterans Aging Cohort Study conducted between September 2001 and June 2002 were included in the study. Physical functioning was measured by self-reported difficulty with various physical activities. Regression analyses were performed to examine demographic and clinical factors associated with physical functioning. Separate models were used for HIV-infected and HIV negative subjects since these groups differed in demographic makeup. In both patient groups, chronic lung disease, coronary artery disease, hypertension, smoking, and major depression were independently associated with reduced physical functioning in age and race adjusted regression models. Increased age was associated with reduced physical functioning in both HIV-infected and HIV-negative patients. However, when comorbid conditions were entered into the models for both HIV-infected and HIV-negative patients, age coefficients were reduced and were no longer statistically significant. Among the HIV-infected patients, results remained unchanged after controlling for the impact of antiretroviral therapy and HIV disease stage. Our findings demonstrate the important role of general medical comorbidity in physical functioning in both HIV-infected and HIV-negative patients. This suggests the importance of effectively treating comorbid conditions in persons with HIV, in order to reduce the overall impact of disease on physical functioning.

Association of chronic obstructive pulmonary disease with frailty measurements in HIV-infected and uninfected Veterans.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) prevalence is increasing among aging HIV-infected individuals. We determined the association between COPD and self-reported measures of frailty [adapted frailty-related phenotype (aFRP)] and physical limitation, and a clinical biomarker of physiologic frailty [Veterans Aging Cohort Study (VACS) Index] in HIV-infected compared with uninfected individuals. DESIGN: Cross-sectional study of VACS participants between 2002 and 2012. METHODS: Prefrail/aFRP was obtained from self-reported surveys. Prefrail was defined as 1-2 domains of physical shrinking, exhaustion, slowness and low physical activity; aFRP was defined as at least 3 domains. Physical limitation scale was determined from 12 self-reported survey items assessing limitations performing physical activities. VACS index includes age and laboratory measurements. We used regression models to test for associations between COPD and outcomes in models stratified by HIV status. RESULTS: The sample included 3538 HIV-infected and 3606 uninfected participants; 67 and 63% were black (P = 0.0003), 97 and 92% were men (P < 0.0001) and 4 and 5% had COPD (P = 0.2). In unadjusted analyses, COPD was associated with all three outcomes (P < 0.0001). In adjusted analyses, COPD was associated with increased prefrail and aFRP in HIV-infected and uninfected participants (P ≤ 0.01 for all comparisons). COPD was associated with physical limitation in both groups (P < 0.0001). There was an interaction between COPD and physical limitation by HIV status with increased physical limitation among HIV-infected participants (P = 0.04). COPD was not associated with VACS index. CONCLUSION: COPD was strongly associated with aFRP and physical limitations. COPD management may mediate frailty through functional limitations rather than physiologic biomarkers, especially in HIV-infected individuals.

Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus-Infected Adults: Veterans Aging Cohort Study.

Importance: With the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)-infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population. Objective: To examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV. Design, Setting, and Participants: Included in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998-2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015. Main Outcomes and Measures: Incident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009. Results: The mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05-1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04-1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05-1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00-1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87-1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI. Conclusions and Relevance: We report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population.

Weight Gain and Incident Diabetes Among HIV-Infected Veterans Initiating Antiretroviral Therapy Compared With Uninfected Individuals.

BACKGROUND: The health implications of weight gain after antiretroviral therapy (ART) for HIV infection are not well characterized and may differ from weight gain among uninfected individuals. We use data from the Veterans Aging Cohort Study to determine whether weight gain after ART has a similar association with incident type 2 diabetes mellitus (DM) as weight gained among HIV-uninfected (uninfected) individuals. METHODS: We explored associations of weight gain and incident diabetes (A1c ≥ 6.5%), in the Veterans Aging Cohort Study, a national observational study of HIV-infected (HIV+) individuals demographically matched 1:2 to uninfected controls. From 2000 to 2011, weight change was assessed in the year following ART initiation for HIV+ individuals and date of first available body mass index for uninfected individuals. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for baseline body mass index using Cox regression. RESULTS: HIV+ individuals had lower prevalence of DM at baseline (12% HIV+, 23% uninfected) and lower incident diabetes (5% HIV+, 11% uninfected). The association of weight gain with risk of DM was linear for HIV+ and uninfected but the slope of the association was steeper for HIV+. For each 5 pounds of weight gained, HIV+ had 14% increased risk of DM (HR, 1.14; 95% CI: 1.10 to 1.17) and uninfected individuals had 8% increased risk (HR, 1.08; 95% CI: 1.07 to 1.10) (P < 0.01 for interaction). CONCLUSIONS: Weight gained in the first year after ART initiation is associated with greater risk of DM than that among uninfected individuals. HIV+ individuals initiating ART who are not underweight should avoid substantial weight gain.

The impact of cigarette smoking on mortality, quality of life, and comorbid illness among HIV-positive veterans.

BACKGROUND: The impact of smoking on outcomes among those with HIV infection has not been determined in the era of highly active antiretroviral therapy (HAART). STUDY OBJECTIVE: Determine the impact of smoking on morbidity and mortality in HIV-positive patients post-HAART. DESIGN: Prospective observational study. PARTICIPANTS: Eight hundred and sixty-seven HIV-positive veterans enrolled in the Veterans Aging Cohort 3 Site Study. MEASUREMENTS: Clinical data were collected through patient questionnaire, International Classification of Diseases--9th edition codes, and standardized chart extraction, and laboratory and mortality data through the national VA database. Quality of life was assessed with the physical component summary (PCS) of the Short-Form 12. RESULTS: Current smokers had increased respiratory symptoms, chronic obstructive pulmonary disease (COPD), and bacterial pneumonia. In analyses adjusted for age, race/ethnicity, CD4 cell count, HIV RNA level, hemoglobin, illegal drug and alcohol use, quality of life was substantially decreased (beta=-3.3, 95% confidence interval [CI] -5.3 to -1.4) and mortality was significantly increased (hazard ratio 1.99, 95% CI 1.03 to 3.86) in current smokers compared with never smokers. CONCLUSIONS: HIV-positive patients who currently smoke have increased mortality and decreased quality of life, as well as increased respiratory symptoms, COPD, and bacterial pneumonia. These findings suggest that smoking cessation should be emphasized for HIV-infected patients.

Food insecurity and health: data from the Veterans Aging Cohort Study.

OBJECTIVE: Food insecurity may be a modifiable and independent risk factor for worse control of medical conditions, but it has not been explored among veterans. We determined the prevalence of, and factors independently associated with, food insecurity among veterans in the Veterans Aging Cohort Study (VACS). METHODS: Using data from VACS from 2002-2008, we determined the prevalence of food insecurity among veterans who have accessed health care in the Veterans Health Administration (VA) as defined by "concern about having enough food for you or your family in the past month." We used multivariable logistic regression to determine factors independently associated with food insecurity and tests of trend to measure the association between food insecurity and control of hypertension, diabetes, HIV, and depression. RESULTS: Of the 6,709 veterans enrolled in VACS, 1,624 (24%) reported being food insecure. Food insecurity was independently associated with being African American, earning <$25,000/year, recent homelessness, marijuana use, and depression. Being food insecure was also associated with worse control of hypertension, diabetes, HIV, and depression (p<0.001). CONCLUSION: Food insecurity is prevalent and associated with worse control of medical conditions among veterans who have accessed care in the VA.

HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction.

BACKGROUND: Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants. We assessed the association between HIV and incident AMI within CVDRF strata. METHODS: Cohort-81,322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched HIV- veterans) participated in this study. Veterans were followed from first clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date (December 31, 2009). Predictors-HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood pressure, blood pressure medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome-Incident AMI [defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates]. Statistics-Cox models adjusted for demographics, comorbidity, and substance use. RESULTS: Of note, 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared with HIV- veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared with HIV- veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0; 95% confidence interval: 1.0 to 3.9; P = 0.044). CONCLUSIONS: The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared with HIV- veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people.

CD8+ T-cells count in acute myocardial infarction in HIV disease in a predominantly male cohort.

Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3) had increased AMI risk (adjusted HR=1.82, P<0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts<200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.

Isometric exercise increases the size of forearm veins in patients with chronic renal failure.

OBJECTIVES: Delay in maturation or failure of maturation of Cimino-Brescia fistulae contributes to the significant vascular access-related morbidity of chronic hemodialysis patients. Increased size and capacitance of native veins before the formation of vascular access has been considered an important variable in the success rate of native fistulae. We evaluated whether a formal exercise program might alter the size of native veins. METHODS: The effect of exercise on venous size was evaluated in 5 patients with severe chronic renal failure [glomerular filtration rate, 30.6 +/- 5.3 mL/min (mean +/- SD)]. Five male patients with a mean age of 57 +/- 9 years underwent a 6-week forearm exercise training program, involving nondominant arms, that included isometric hand-grip contractions to 25 to 35% of MVC lasting 40 to 120 seconds and repetitive squeezing of squash and racquet balls. Both the volume and intensity of exercise training was increased weekly based on strength measured by hand-grip dynamometer and on the patients' indicated level of comfort. Cephalic vessel size in both the nondominant (trained) and dominant (control) arms, with and without a tourniquet, were obtained using Doppler ultrasound before and after the 6-week exercise training program. RESULTS: The size of the cephalic vein of the exercised arm increased significantly ( < 0.05) compared with the control arm when measured in both the absence (048 +/- 0.016 versus 0.024 +/- 0.023 cm ) and the presence of a tourniquet (0.056 +/- 0.022 versus 028 +/- 0.027 cm ). CONCLUSIONS: These findings indicate that a simple, incremental resistance, exercise-training program can cause a significant increase in the size of the cephalic vein commonly used in the creation of an arteriovenous fistula. The increase in size and resultant probable increase in blood flow might accelerate the maturation of native arteriovenous fistulae, thereby lessening the morbidity associated with vascular access.

An adapted frailty-related phenotype and the VACS index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals.

BACKGROUND: Frailty is a geriatric syndrome of decreased physiologic reserve and a risk factor for hospitalization and mortality. We hypothesized that an adapted survey-based frailty-related phenotype (aFRP) predicts hospitalization and mortality among HIV-infected and uninfected individuals in adjusted models but is uncommon among those achieving undetectable HIV-1 RNA. METHODS: Defined from self-reported domains of physical shrinking, exhaustion, slowness, and low physical activity in Veterans Aging Cohort Study (VACS) participants, aFRP was considered present with ≥3 domains and prefrailty with 1-2 domains. Cox survival analysis determined hazard ratios (HRs) for 5-year hospitalization and mortality risk adjusting for frailty states, demographics, health behaviors, comorbidities, and a validated risk index incorporating HIV-specific and general organ system biomarkers, the VACS Index. Model discrimination was assessed. RESULTS: Participants with complete data were included [6515/7324 (89%)]. Of these, 3.9% of HIV-infected individuals with HIV-1 RNA >400 copies per milliliter; 2.0% of HIV-infected individuals with HIV-1 RNA ≤400 copies per milliliter; and 2.8% of uninfected individuals met aFRP criteria (P = 0.01). After adjustment for other covariates, aFRP was associated with hospitalization (HR = 1.78; 95% confidence interval: 1.48 to 2.13) and mortality (HR = 1.75; 95% confidence interval: 1.28 to 2.40). C-statistics for the VACS Index for hospitalization (0.633) and for mortality (0.756) were higher than for aFRP (0.565 and 0.584, respectively). C-statistic for hospitalization improved modestly when VACS Index and aFRP were both included (0.646) and minimally for mortality (0.761). CONCLUSIONS: aFRP was independently associated with adverse health outcomes among HIV-infected and uninfected individuals. aFRP modestly improved prediction for hospitalization. However, the aFRP is rare among HIV-infected individuals with undetectable HIV-1 RNA.

Association of the veterans aging cohort study index with exercise capacity in HIV-infected adults.

Physical disability is a major priority in aging, affecting morbidity, mortality, and quality of life. Despite the large number of adults aging with HIV, our understanding of the physiologic and clinical risk factors for disability is limited. Our goal is to determine whether the Veterans Aging Cohort Study (VACS) Index, based on routine clinical blood tests, could serve as a point of care screening tool to identify HIV-infected adults at high risk for physical disability. HIV-infected adults enrolled in the VACS participated in a cross-sectional exercise study with established measures of strength and endurance. The VACS Index was calculated using recent clinical laboratory values and age; a higher score reflects greater mortality risk. Statistical analyses included correlation and linear regression models adjusted for muscle mass. Fifty-five HIV-infected adults, predominantly African-American men, were included with age mean±SD of 52±7 years. Median (IQR) CD4 cell count was 356 cells/mm(3) (212-527). The VACS Index was inversely correlated with quadriceps strength (r=-0.45, p<0.01), grip strength (r=-0.28, p=0.04), and 6-min walk distance (r=-0.27, p=0.05). A 20-point increase in VACS Index score was associated with a 10% lower leg strength (p<0.01), which remained significant after adjustment for muscle cross-sectional area (p=0.02). The VACS Index explained 31% of the variance in specific leg strength. In this group of middle-aged adults with well-controlled HIV infection the VACS Index was significantly associated with upper and lower extremity strength. The VACS Index may be valuable for identification of patients at high risk for disability due to muscle weakness.

Impact of cigarette smoking on mortality in HIV-positive and HIV-negative veterans.

It is unknown whether smoking confers similar mortality risk in HIV-positive as in HIV-negative patients. We compared overall mortality stratified by HIV and smoking of 1,034 HIV-positive block-matched to 739 HIV-negative veterans, enrolled 2001-2002 in the Veterans Aging Cohort 5 Site Study. Adjusted incidence rate ratios (IRR) for mortality were calculated using Poisson regression. Mortality was significantly increased in HIV-positive veterans according to both smoking status and pack-years in unadjusted and adjusted analyses (adjusted IRR 2.31, 95% confidence interval [CI] 1.53-3.49 for HIV-positive current smokers and IRR 1.32, 95% CI 0.67-2.61 for HIV-negative current smokers). Comorbid diseases were also significantly increased according to smoking status and pack-years. Current smoking is associated with poor outcomes; even lower levels of exposure appear to be detrimental in HIV-infected veterans. These findings support the need for improvements in smoking cessation and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV.

Veterans Aging Cohort Study (VACS): Overview and description.

BACKGROUND: The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study. OBJECTIVES: We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample. RESEARCH DESIGN: We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection. MEASURES: Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA "paperless" electronic medical record system. RESULTS: More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age-race-site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control. CONCLUSIONS: VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.