HIV infection doubled the risk of a heart attack for patients receiving care at Boston’s two largest hospitals between 1996 and 2004, even after controlling for all the accepted risk factors for heart disease, researchers from Massachusetts General Hospital report in an article released early online by the Journal of Clinical Endocrinology and Metabolism.
The effect of HIV on heart attack rates was especially pronounced in women, who made up nearly one-third of the HIV-positive study cohort.
Overall, HIV-positive people had a 50% increased risk of heart attack when compared to HIV-negative people, but HIV-positive women had a 300% increased risk of heart attack when compared with HIV-negative people even after taking into account age, race, high blood pressure (hypertension), diabetes and elevated lipid levels.
“Our study shows a higher incidence of myocardial infarction [heart attack] and major cardiovascular risk factors in HIV-infected patients, compared with noninfected patients," said Dr Steven Grinspoon of the Massachusetts General Hospital Program in Nutritional Metabolism and Neuroendocrine Unit, the report's senior author.
"Those findings indicate that those infected with HIV should be assessed for cardiovascular risk factors and that we urgently need to develop strategies to modify those risks," he said.
A number of studies have now shown an increased risk of cardiovascular disease in HIV-positive people receiving antiretroviral treatment. The largest study, the DAD study, found a 17% increase in risk during each of the first six years of antiretroviral therapy, the equivalent of 3.6 myocardial infarctions (heart attacks) per 1,000 patient years of follow-up.
But the Massachusetts General study found a much higher rate: 11.1 per 1,000 patient years for HIV-positive patients and 6.98 per 1,000 patient years for HIV-negative patients after controlling for cardiovascular risk factors including age.
The researchers say the difference could be explained by the inclusion of a greater number of older patients in the Boston cohort (although people over 55 contributed just 5% of person-years of HIV-positive follow-up), and by the fact that the background rate of heart attack in the US population is higher (the DAD study was conducted largely in European patients). They note that the rates seen were similar to the large Framingham study of heart disease incidence, which is a touchstone study used to predict the risk of heart disease for millions of patients.
The researchers used the Research Patient Data Registry, a database of demographic and diagnostic information on more than 1.7 million patients treated at MGH and Brigham and Women's Hospital since 1996. They compared information on almost 4,000 HIV-infected patients with data from more than one million patients without HIV. Study participants were aged 18 to 84 and were seen at least twice during the study period of almost eight years. Any patient whose initial visit was for a heart attack was excluded from the study group.
The HIV cohort contributed 16,983 patient years of follow-up (mean follow-up 4.5 years), and the HIV-negative cohort contributed 3,747,329 years of follow-up (mean follow-up 3.7 years).
The median age of HIV-positive patients was 38, and HIV-positive men in younger age groups contributed a greater percentage of the person-year follow-up than did HIV-negative men.
HIV-positive patients were more likely to have been exposed to a protease inhibitor than a non-nucleoside reverse transcriptase inhibitor (63% vs 48%), but drug utilisation was only reported for 1,579 of the 3,851 patients, preventing any analysis of heart attack risk according to drug exposure.
Hypertension (21% vs 17%), diabetes (11% vs 6%) and dyslipidemia (23% vs 17%) were all significantly more common in HIV-positive patients, male and female (P
The researchers looked for reports of myocardial infarction recorded in the hospital database, and found 189 HIV-positive patients and 26,142 HIV-negative patients experienced an MI during the follow-up period.
As noted previously, the risk of heart attack was higher in the HIV cohort. The unadjusted relative risk was 1.53 (95% confidence interval 1.32-1.75, p
When examining the contribution of individual risk factors, dyslipidemia (RR 3.5), diabetes (RR 3.3) and hypertension (RR 3.0) were associated with the greatest increase in the risk of heart attack across both HIV-positive and HIV-negative cohorts.
HIV on its own increased the risk by 2.01 (p
Among HIV-positive patients dyslipidemia (RR 3.65) and African-American race (RR 1.43) were the only significant risk factors for heart attack.
Insufficient data on smoking were available to arrive at a reliable estimate of its contribution, since details of smoking habits had been recorded for only 22% of HIV-positive patients, and it could not be added to the model. Although the authors suggest that a higher rate of smoking in the HIV-positive group (38% vs 18% current, 57% vs 40% ever) could be one explanation for the higher heart attack rate, further research is needed. (In the DAD study smoking was associated with an increased risk of heart attack but there was no comparison with an HIV-negative control group).
Women with HIV had a higher risk of heart attack than HIV-positive men (RR 2.98 vs RR 1.4) after adjusting for other risk factors, and previous research by the same group has shown that fat redistribution in HIV-positive women caused by antiretroviral therapy is associated with increases in cardiovascular risk markers including lipids and C-reactive protein. The authors suggest that changes in body composition among HIV-positive women in this cohort may partly explain the increased risk of heart attack in women.
"Follow-up studies are needed to better determine why myocardial infarction rates are higher in HIV patients, which risk factors drive this risk most, and how smoking – which we weren't able to completely evaluate in this study – affects this risk," Dr Grinspoon said.
"We also need to analyse the relationship of antiretroviral medications to cardiovascular risk. HIV medications save lives, and patients should continue taking them as prescribed; but we want physicians to be aware of these increased heart attack rates, watch risk factors carefully and appropriately target their treatment."
The findings were previously presented as a poster at the Sixteenth International AIDS Conference in Toronto in 2006.
Triant VA et al. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with HIV disease. J Clin Endocrin Metab 2007 (advance online publication).