People who are infected with HIV, especially those on long-term antiretroviral therapy (ART) or who use cocaine, have a high prevalence of LV dysfunction. Since ART use could lead to diabetes, and since cardiac steatosis (fatty heart) has been identified in those with diabetes, it is critical to examine whether HIV infection, ART use, and cocaine use promote cardiac steatosis, a marker for cardiomyopathy. Virtually no reported studies have addressed the combined effects of HIV infection, ART use, and cocaine use on the etiology of cardiomyopathy. According to our preliminary study, cardiac steatosis is prevalent in HIV-infected individuals, especially those on ART. These results are entirely new and never before reported. This application seeks support for conducting novel research on the effects of HIV infection, ART use, and cocaine use on cardiac steatosis. The proposed study, using the cohort of study participants enrolled in the ongoing study DA12777, will employ magnetic resonance imaging (MRI) to accurately quantify the ectopic fat deposition in the myocardium and will explore the association between HIV infection, ART use, cocaine use, and cardiac steatosis. The proposed specific aims of this study are (1) To estimate the prevalence and incidence of cardiac steatosis and left ventricular (LV) dysfunction in cardiovascularly asymptomatic men and women with one of the following characteristics: HIV(-) and cocaine(-);HIV(-) and cocaine(+);HIV(+) and cocaine(-) and ART(-);HIV(+) and cocaine(-) and ART(+);HIV(+) and cocaine(+) and ART(-);and HIV(+) and cocaine(+) and ART(+);(2) To examine the effects of HIV infection on the presence and development of cardiac steatosis and regional LV dysfunction;(3) To examine the effects of the various classes of ART and individual ART on the presence and development of cardiac steatosis and regional LV dysfunction in HIV-infected persons;(4) To examine the effects of cocaine use on the presence and development of cardiac steatosis and regional LV dysfunction;(5) To examine the joint effects of HIV infection, ART use, and cocaine use on the presence and development of cardiac steatosis and regional LV dysfunction;and (6) To investigate the direct effects and mechanisms of HIV infection, ART use, and cocaine use on mitochondrial damage. This study will be among the first, if not the very first, to explore the mechanisms of premature HIV/cocaine-related cardiomyopathy, and its findings may lead to a breakthrough in research on prevention/intervention related to heart failure in HIV-infected persons and to translation of scientific discoveries into clinical applications.
This study will investigate why HIV-infected African Americans have high rates of cardiac steatosis and regional left ventricular dysfunction. The study could provide critical information for understanding the mechanisms of premature heart failure 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.
|Lai, Shenghan; Heaphy, Christopher M; Rizzo, Anthony J et al. (2018) Cocaine use may induce telomere shortening in individuals with HIV infection. Prog Neuropsychopharmacol Biol Psychiatry 84:11-17|
|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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