HIV increases the risk of heart attack, even in people with a suppressed viral load

Infection with HIV is associated with an increased risk of heart attack, investigators from the United States report in the Journal of the American Medical Association Internal Medicine. Importantly, this finding was based upon comparison of HIV-positive and HIV-negative individuals with the same demographic and cardiovascular-risk profiles. Overall, infection with HIV was associated with a 50% increase in the risk of heart attack beyond that explained by other risk factors.

“HIV infection is independently associated with AMI [acute myocardial infarction, or heart attack] after adjusting for Framingham risk, comorbidities, and substance abuse,” comment the investigators.

Cardiovascular disease is an increasingly important cause of serious illness and death in people with HIV. Earlier research has found an association between infection with HIV and an increased risk of heart attack. However, for the most part these studies did not adequately control for confounding factors or had an inadequate control population of HIV-negative people.

Investigators from the Veterans Aging Cohort Study (VACS) Virtual Cohort (VC) therefore designed a large study with well-matched patients and controls to examine whether HIV infection was associated with an increased risk of heart attack, after taking into account standard risk factors used to calculate Framingham risk scores (ten-year risk of cardiovascular disease), co-infections such as hepatitis C virus, and smoking, drug and alcohol use.

The study population comprised approximately 84,500 individuals who were prospectively monitored between 2003 and 2009. Some 27,350 individuals were HIV positive. The HIV-negative controls were well matched in terms of demographic characteristics. The mean age was approximately 48 years, 97% of participants were male and 48% were African Americans.

The Framingham risk score for both groups was six, and the overall cardiovascular-risk profiles were simiular for the patients and the controls. However, the HIV-infected participants were somewhat more likely to smoke, and to have high triglycerides and lower HDL cholesterol.

During a median of 5.9 years of follow-up, there were 871 heart attacks, 42% of which involved people with HIV.

After taking into account Framingham risk factors, co-infections and substance abuse, HIV-positive participants were approximately 50% more likely to experience a heart attack compared to the HIV-negative controls (HR = 1.48; 95% CI, 1.27-1.72).

The associations between infection with HIV and an increased risk of heart attack persisted when analysis was restricted to participants who had never smoked (HR =1.75; 95% CI, 1.27-2.42) and those without hepatitis C virus, renal disease or obesity (HR = 1.50; 95% CI, 1.20-1.88). Expansion of the study population to include other data sets similarly showed an independent association between HIV and an increased risk of heart attack (HR = 1.58; 95% CI, 1.25-1.99).

Risk of heart attack was highest for HIV-positive people with a low CD4 cell count (p = 0.04) and a detectable viral load (p = 0.05). However, even participants with a viral load below 500 copies/ml had an increased risk of heart attack (HR = 1.39; 95% CI, 1.17-1.66).

The investigators then restricted their analysis to the participants with HIV. A recent viral load above 500 copies/ml (HR = 1.60; 95% CI, 1.14-2.22) and recent CD4 cell count below 200 cells/mm³ (HR = 1.57; 95% CI, 1.10-2.24) were both associated with heart attack. Treatment with a protease inhibitor was of borderline significance (HR = 1.34; 95% CI, 0.98-1.81; p = 0.06) when included in a model that adjusted for Framingham risk scores, co-infections and drug and alcohol use.

“Veterans with HIV infection have a significantly higher risk of AMI compared with demographically and behaviorally similar uninfected veterans even after adjusting for Framingham risk factors, comorbidities and substance abuse,” comment the investigators. “Findings from this and prior studies suggest that the increased risk of AMI among HIV-positive people is likely a function of HIV, ART, and the burden of comorbid disease including Framingham risk factors.”

However, the investigators emphasise that the HIV-positive participants and controls had the same baseline Framingham risk profiles. They therefore suggest that: “Framingham risk score may underestimate AMI risk among HIV-positive people and that the addition of HIV and ART to a model of established AMI risk factors may be clinically useful.”

Freiberg MS et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med, online edition. DOI: 10.1001/jamainternmed.2013.3728, 2013.