African Americans (AAs) in the US are greatly over-represented not only among persons affected by HIV/AIDS and cocaine addiction, but also among persons affected by coronary artery disease (CAD) associated with HIV infection, antiretroviral therapy (ART), and cocaine use. According to our preliminary study, the rate of presence of coronary plaques/stenosis was disturbingly high in HIV-infected cardiovascularly asymptomatic AAs (27%). The rate was even higher in those who were long-term ART users or long-term cocaine users. Thus, it is critical to estimate the prevalence and incidence of coronary plaques and coronary luminal obstruction caused by both calcified and noncalcified plaques in that participating population and to examine the risk factors for coronary plaques and coronary luminal obstruction in HIV-infected cardiovascularly asymptomatic AAs. Also, since there is only a limited understanding of the mechanisms involved in the development of premature CAD in HIV-infected persons, a mechanistic study in vivo is proposed with the use of endothelial dysfunction markers and the most advanced imaging technologies to quantify coronary endothelial dysfunction - the earliest stage of atherosclerosis. The proposed specific aims are (1) To estimate the prevalence and incidence of metabolic and anthropometric abnormalities, coronary plaques, significant coronary stenoses, and left ventricular (LV) dysfunction;(2) To examine the effects of the severity of HIV infection, as measured by HIV viral load and CD4 nadir, on the presence and development of significant coronary stenoses, coronary plaques, plaque composition, and LV dysfunction;(3) To examine the effects of long-term ART (all classes), especially PI-based ART, on the presence and development of significant coronary stenoses, coronary plaques, plaque composition, and LV dysfunction;(4) To examine how cocaine use modifies the effects of the various classes of ART on the presence and development of significant coronary stenoses, coronary plaques, plaque composition, and LV dysfunction;(5) To longitudinally examine the risk factors for cardiovascular events in HIV-infected AAs with coronary plaques and significant coronary stenoses;(6) To investigate the direct effects and mechanisms of HIV infection, ART use, and cocaine use on endothelial dysfunction, as measured by endothelium-derived markers;and (7) To assess the direct effects and mechanisms of HIV infection, ART use, and cocaine use on coronary endothelial dysfunction, as measured with the use of N-13-ammonia PET/CT imaging. This study could provide critical information for understanding the mechanisms of premature CAD and lead to a breakthrough in research on prevention/intervention of CAD in HIV-infected persons and to translation of scientific discoveries into clinical applications.

Public Health Relevance

This study will investigate why HIV-infected African Americans have high rates of heart disease. The study could provide critical information for understanding the mechanisms of premature heart disease and lead to a breakthrough in research on prevention/intervention of heart disease in HIV-infected persons and to translation of scientific discoveries into clinical applications.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA025524-03
Application #
7883687
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Khalsa, Jagjitsingh H
Project Start
2008-09-30
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
3
Fiscal Year
2010
Total Cost
$750,934
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Li, Ji; Lai, Hong; Chen, Shaoguang et al. (2017) Gender differences in the associations between urinary bisphenol A and body composition among American children: The National Health and Nutrition Examination Survey, 2003-2006. J Epidemiol 27:228-234
Lai, Shenghan; Gerstenblith, Gary; Moore, Richard D et al. (2017) Cocaine use may modify HIV/ART-associated myocardial steatosis and hepatic steatosis. Drug Alcohol Depend 177:84-92
Sandfort, Veit; Bluemke, David A; Vargas, Jose et al. (2017) Coronary Plaque Progression and Regression in Asymptomatic African American Chronic Cocaine Users With Obstructive Coronary Stenoses: A Preliminary Study. J Addict Med 11:126-137
Lai, Hong; Moore, Richard; Celentano, David D et al. (2016) HIV Infection Itself May Not Be Associated With Subclinical Coronary Artery Disease Among African Americans Without Cardiovascular Symptoms. J Am Heart Assoc 5:e002529
Lai, Hong; Stitzer, Maxine; Treisman, Glenn et al. (2015) Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study. J Addict Med 9:331-9
Lai, Shenghan; Gerstenblith, Gary; Li, Ji et al. (2015) Chronic cocaine use and its association with myocardial steatosis evaluated by 1H magnetic resonance spectroscopy in African Americans. J Addict Med 9:31-9
Liu, Chia-Ying; Bluemke, David A; Gerstenblith, Gary et al. (2014) Reference values of myocardial structure, function, and tissue composition by cardiac magnetic resonance in healthy African-Americans at 3T and their relations to serologic and cardiovascular risk factors. Am J Cardiol 114:789-795
Liu, Chia-Ying; Bluemke, David A; Gerstenblith, Gary et al. (2014) Myocardial steatosis and its association with obesity and regional ventricular dysfunction: evaluated by magnetic resonance tagging and 1H spectroscopy in healthy African Americans. Int J Cardiol 172:381-387
Lai, Shenghan; Fishman, Elliot K; Gerstenblith, Gary et al. (2013) Vitamin D deficiency is associated with coronary artery calcification in cardiovascularly asymptomatic African Americans with HIV infection. Vasc Health Risk Manag 9:493-500

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