CORRELATES OF DRUG USE AND HEART DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1. BACKGROUND 1.1. Cocaine Abuse and Its Effect on the Cardiovascular System The most recent report from the Substance Abuse and Mental Health Services Administration revealed that an estimated 1.7 million Americans aged 12 years or older were current cocaine users, and 406,000 were current crack users. As cocaine abuse has become widespread, cocaine-related cardiovascular events have increased dramatically. Most studies of the impact of cocaine on cardiovascular complications have focused on clinical events; the impact of cocaine use on subclinical coronary artery disease has not yet been thoroughly investigated. A number of cardiovascular diseases associated with cocaine use have been reported, including chest pain, myocardial ischemia and infarction, myocarditis, dilated cardiomyopathy, congestive heart failure, cardiac arrhythmias, and sudden death, as well as coronary spasm, aortic dissection, atherosclerosis, and pathologic alterations in the blood vessels. 1.2. HIV Infection and Its Effect on the Cardiovascular System Despite recognition that HIV infection is an important causal factor for developing cardiovascular complications, such as dilated cardiomyopathy and pericardial effusion, most investigations have focused on clinical diseases. Since 1993, HIV infection has been the leading cause of death among those aged 25-45 years in the United States. As of the end of 2002, an estimated total of 384,906 persons living with AIDS had been reported to the CDC, and 42% of them were black. HIV infection was associated with cardiovascular abnormalities in 45% to 50% of HIV-infected persons, and even higher incidences of cardiovascular involvement have been reported in patients with AIDS. 1.3. Combined Effect of Cocaine Abuse and HIV The combination of cocaine abuse and HIV infection represents a unique challenge to both researchers and health practitioners. Illicit drug use, particularly by injection, has been associated closely with the HIV epidemic. According to the 2002 report from CDC, about one fourth of the newly reported AIDS cases in the United States occurred in persons with a history of drug use. Both HIV infection and cocaine abuse can cause accelerated atherosclerosis and cardiovascular complications, possibly resulting from separate mechanisms. With longer survival achieved by more effective antiretroviral treatment, an increasing number of HIV-infected patients, who have a higher rate of cocaine abuse than the normal population, may face more serious threats from cardiovascular complications. 1.4. Side Effects of Protease Inhibitors Most of the highly active antiretroviral therapy (HAART) regimens contain HIV PIs. Premature coronary artery disease (CAD) has been reported in patients on PI-containing regimens of HAART. Patients taking PIs have been found to have a number of side effects, including fatty deposits in the abdomen (Crix belly) and back (Buffalo humps). Changes in lipid and carbohydrate metabolism in patients on protease inhibitors have also been reported: Glucose, triglyceride, and cholesterol levels increased significantly more in patients receiving than in those not receiving PIs. The changes in lipid metabolism brought about by PIs in the presence of continued cocaine use deserve further investigations. Although the data have suggested that PI-containing regimens may be associated with the development of coronary artery disease, we are one of a few groups that have published papers suggesting PIs are associated with subclinical atherosclerosis and left ventricular dysfunction. 2. Justification for the Proposed Study 1. Although several studies on HIV, cocaine, and cardiovascular disease have been published, a systematic evaluation of the relationships of these factors with subclinical disease has rarely been conducted. Because antiretroviral medications containing PIs may adversely affect the development of subclinical atherosclerosis and left ventricular dysfunction and because regimens containing PIs have become standard therapy, a prospective, well-designed study is urgently needed to provide critical information in this area. Since non-PI medications, such as NRTI, may also have adverse effects on lipid profiles [54], in addition to using non-PIs as a control group, this proposed study will also use those participants with HIV who are not on any antiretroviral medications as a control group. 2. Although the current ongoing study has generated some new information about the effect of cocaine, HIV infection, and its therapy on subclinical atherosclerosis, longer observational periods and a larger sample are needed to establish what combined effect that cocaine, HIV, and its therapy with antiretroviral medications may have on cardiovascular risk. This need is especially true when coronary stenosis is investigated. 4. Study Design This collaborative investigation entails continuation of our current study of the effects of cocaine and HIV infection on subclinical atherosclerosis in black men and women in Baltimore, Maryland. The purposes of this proposed study are: (1) to exploit ongoing follow-up of the cohort of study participants who have participated in this ongoing study in order to prospectively study several critical scientific questions regarding the combined effects of HIV and cocaine, and the combined effects of cocaine and HIV therapy with antiretroviral medications; (2) to acquire the statistical power to detect the combined effects of cocaine and HIV infection, we also will recruit additional study participants aged 25 to 45 years; and (3) to assess how age interacts with cocaine, HIV infection, and its therapy using antiretroviral drugs for subclinical atherosclerosis, we also will recruit study participants at least 46 years old and study participants with hypertension. We plan to continue to follow up our study participants through the currently funded end of this study (05/2005), which will provide a total of at least 2 years of follow-up for study participants enrolled in 2003. 5. Study Population African Americans residing in inner-city of Baltimore. 6. Outcome measures (1) Coronary artery calcification parameters. (2) LV functional parameters include ejection fraction (EF), systolic/diastolic volume, LV mass, wall motion. (3) Coronary vessel detail and coronary plaque burden and plaque composition.