In studies using population controls, HIV infection has been associated with increased risk of cardiovascular disease (CVD). However, this risk may be partially explained by factors other than HIV or its treatment including higher rates of smoking, alcohol abuse, cocaine use, hepatitis C infection and renal disease. Equally important, major mechanisms of CVD among those with HIV likely differ from those without infection because lipid abnormalities occur abruptly--after initiation of combination antiretroviral therapy (CART), and because of inflammatory effects of HIV and HCV, toxic effects of alcohol and vasospasm due to cocaine. The Veterans Aging Cohort Study (VACS) is an ongoing, multicenter, prospective study of 3227 veterans with HIV infection and 3240 age/race/site matched HIV uninfected controls. Teamed with internationally recogized experts in CVD, we propose to supplement the rich clinical data available in this cohort with adjudicated CVD endpoints, and biomarkers and measures of CVD risk including: dyslipidemia, insulin resistance , markers of inflammation, cardiac structural and functional abnormalities, body composition changes, subclinical atherosclerosis, cardiac fitness, and alterations associated with thrombogenesis and fibrinolysis. With these enriched data we will be uniquely positioned to determine whether: 1) HIV infection is an independent risk factor for CVD endpoints and whether HCV, substance use and CART modify the association between HIV and CVD endpoints, 2) biomarkers and measures of CVD risk are increased among those with HIV infection and CART nonadherence, and 3) biomarkers and measures of CVD risk are increased among those with HCV infection and substance use. Importantly, we will adjust for both CART adherence and competing risk, since HIV infected individuals have a substantially higher mortality rate. The large, well characterized, older, predominantly minority patient sample with excellent longitudinal follow up and high prevalence of HCV and substance use, comprehensive pharmacy data, and established access to comprehensive electronic medical records are important leveraged strengths of this application. The strong CVD expertise, established analytic and mentoring skills of the VACS team, and a multi-PI plan incorporating a promising new investigator ensure that this proposal will effectively advance our understanding of CVD outcomes and mechanisms among HIV infected and uninfected individuals.

Public Health Relevance

Cardiovascular disease (CVD) is an important health problem among people infected with Human Immunodeficiency Virus (HIV). Whether CVD risk is associated with the HIV virus, treatment for HIV or health problems associated with HIV is not known. Compared with people who are not infected with HIV, HIV infected people have higher rates of smoking, alcohol abuse, cocaine use, and hepatitis C. Thus it is important to compare rates of CVD among those with HIV infection to those without HIV infection who are behaviorally and demographically similar. This proposal will improve our understanding of CVD risk among people infected with HIV.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095136-05
Application #
8322045
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Program Officer
Mcdonald, Cheryl
Project Start
2008-09-25
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$1,057,149
Indirect Cost
$238,498
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Rentsch, Christopher; Tate, Janet P; Akgün, Kathleen M et al. (2016) Erratum to: Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United States Veterans from 1997 to 2011. AIDS Behav 20:565
Rentsch, Christopher; Tate, Janet P; Akgün, Kathleen M et al. (2016) Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United States Veterans from 1997 to 2011. AIDS Behav 20:555-64
Hanna, David B; Guo, Mengye; Bůžková, Petra et al. (2016) HIV Infection and Carotid Artery Intima-media Thickness: Pooled Analyses Across 5 Cohorts of the NHLBI HIV-CVD Collaborative. Clin Infect Dis 63:249-56
Herrin, Melissa; Tate, Janet P; Akgün, Kathleen M et al. (2016) Weight Gain and Incident Diabetes Among HIV-Infected Veterans Initiating Antiretroviral Therapy Compared With Uninfected Individuals. J Acquir Immune Defic Syndr 73:228-36
Salinas, Jorge L; Rentsch, Christopher; Marconi, Vincent C et al. (2016) Baseline, Time-Updated, and Cumulative HIV Care Metrics for Predicting Acute Myocardial Infarction and All-Cause Mortality. Clin Infect Dis 63:1423-1430
Justice, Amy C; McGinnis, Kathleen A; Tate, Janet P et al. (2016) Risk of mortality and physiologic injury evident with lower alcohol exposure among HIV infected compared with uninfected men. Drug Alcohol Depend 161:95-103
So-Armah, Kaku A; Tate, Janet P; Chang, Chung-Chou H et al. (2016) Do Biomarkers of Inflammation, Monocyte Activation, and Altered Coagulation Explain Excess Mortality Between HIV Infected and Uninfected People? J Acquir Immune Defic Syndr 72:206-13
Viswanathan, Shilpa; Justice, Amy C; Alexander, G Caleb et al. (2015) Adherence and HIV RNA Suppression in the Current Era of Highly Active Antiretroviral Therapy. J Acquir Immune Defic Syndr 69:493-8
White, Jessica R; Chang, Chung-Chou H; So-Armah, Kaku A et al. (2015) Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study. Circulation 132:1630-8
Paisible, Anne-Lise; Chang, Chung-Chou H; So-Armah, Kaku A et al. (2015) HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction. J Acquir Immune Defic Syndr 68:209-16

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