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 recognized 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. 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.

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 #
5R01HL095136-02
Application #
7691239
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
2009-07-01
Budget End
2010-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$835,848
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Beckman, Joshua A; Duncan, Meredith S; Alcorn, Charles W et al. (2018) Association of Human Immunodeficiency Virus Infection and Risk of Peripheral Artery Disease. Circulation 138:255-265
Eyawo, Oghenowede; McGinnis, Kathleen A; Justice, Amy C et al. (2018) Alcohol and Mortality: Combining Self-Reported (AUDIT-C) and Biomarker Detected (PEth) Alcohol Measures Among HIV Infected and Uninfected. J Acquir Immune Defic Syndr 77:135-143
Patterson, Olga V; Freiberg, Matthew S; Skanderson, Melissa et al. (2017) Unlocking echocardiogram measurements for heart disease research through natural language processing. BMC Cardiovasc Disord 17:151
Taylor, Barbara S; So-Armah, Kaku; Tate, Janet P et al. (2017) HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D-Dimer. J Acquir Immune Defic Syndr 75:500-508
Freiberg, Matthew S; Chang, Chung-Chou H; Skanderson, Melissa et al. (2017) Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study. JAMA Cardiol 2:536-546
So-Armah, Kaku A; Lim, Joseph K; Lo Re, Vincent et al. (2017) FIB-4 stage of liver fibrosis predicts incident heart failure among HIV-infected and uninfected patients. Hepatology 66:1286-1295
Hanna, David B; Guo, Mengye; B?žková, 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
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
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
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

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