Background: Preliminary physiologic and clinical data suggest that use of highly active antiretroviral therapy may lead to premature cardiovascular disease. We assessed the incidence of coronary heart disease (CHD) (MI or unstable angina) and cerebrovascular disease (CVD) (ischemic stroke or TIA) in a large Maryland clinical cohort in which comprehensive demographic, clinical and therapeutic data have been collected longitudinally since 1990.

Methods: A nested case control study was designed to assess factors associated with CVD and CHD. Non-CHD and non-CVD patients (pts) were randomly selected from the overall cohort; 5 controls per case were identified and matched on cohort enrollment date and duration of follow-up. Mantel-Haenszel chi-square and conditional logistic regression analyses were used to assess risk factors.

Results: Of 2,671 pts followed for 7,330 person-years (PY) after January 1, 1996, there was 43 CHD and 37 CVD events for an incidence rate of 5.9 events/1000 PY and 5.0 events/1000 PY, respectively. Factors associated (p < 0.05) with having a CHD or CVD event included age (mean = 46 years-cases, 41 years-controls), cholesterol (mean 186 g/dl cases, 156 g/dl controls), prior diabetes (15% cases, 7% controls), prior hypertension (43% cases, 17% controls), CD4 (mean 351 cells/mm3 cases, 251 cells/mm3 controls). There was no difference between cases and controls in race, injecting drug use, or HIV-1 RNA. Cases were significantly more likely than controls to receive protease inhibitors (PI) (59% vs 43%) and D4T (63% cases, 43% controls); however, no differences were found for other nucleoside RTIs, NNRTs, or any individual PI. The risk factors were similar for CHD and CVD when assessed separately.

Conclusions: Based on National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, the age-sex-race population rates of CHD and CVD would be expected to be 2/1000 PY and 3/1000 PY, respectively. Compared to national CHD and CVD rates, the incidence rates of CHD and CVD in our cohort are approximately 2–3 times higher than expected. These event rates are associated not only with expected cardiovascular risk factors, but also with antiretroviral drug use.