People with HIV have higher risk of death after heart attack

People with HIV had higher mortality than HIV-negative individuals after hospitalisation for acute coronary syndrome, but the excess risk disappeared for people on antiretroviral therapy with high CD4 cell counts, researchers reported last week at the IDWeek 2013 conference in San Francisco.

People with HIV are at higher risk for cardiovascular disease, but whether this is due to the virus itself, resulting inflammatory and metabolic changes, antiretroviral toxicities or other factors is not yet fully understood. 

Few studies have looked at outcomes amongst people with HIV following acute coronary syndrome (ACS), which includes heart attacks (myocardial infarction), unstable angina (chest pains) and other conditions caused by blockage of blood vessels supplying the heart muscle.

Michael Silverberg and colleagues with Kaiser Permanente, a large managed-care organisation in the US, asked whether HIV status, immune deficiency or antiretroviral therapy (ART) use affects long-term survival following ACS hospitalisation. The Kaiser team previously reported that HIV-positive people had a 40 to 50% higher risk of myocardial infarction compared with HIV-negative people seen at their facilities.

This analysis included all patients hospitalised for the first time with ACS at Kaiser Permanente Northern California between 1996 and 2010. Of these, 226 were HIV positive and 86,321 were HIV negative. Silverberg noted that, in the San Francisco area, more than half the population of people with HIV are now over 50 years of age.

People were included if they had ST-elevation myocardial infarction (STEMI) – typically the more severe type, non-ST myocardial infarction (NSTEMI) or unstable angina. Deaths were determined based on hospital records, California death certificates and Social Security Administration files.

HIV-positive ACS patients were more likely than their HIV-negative counterparts to be men (94 vs 63%, respectively) and were younger on average (54 vs 67 years). Within the HIV-positive group, 75% were white, 17% were black and 9% were Hispanic, Asian or 'other'; in the HIV-negative group the corresponding percentages were 78, 8 and 15%.

Amongst people with HIV, 58% were taking protease inhibitor-based ART, 26% were on protease-sparing ART and 16% were not on ART. About 20% had CD4 counts under 200 cells/mm³, nearly half had counts between 200 and 499 cells/mm³ and one-third had counts above 500 cells/mm³.

People with HIV were more likely to be hospitalised with STEMI (37 vs 25%), both groups were equally likely to have NSTEMI (about 33%) and HIV-negative patients were more likely to have unstable angina (28 vs 42%).

About 13% in both groups had elevated LDL or 'bad' cholesterol, but the HIV-positive group was significantly more likely to have low HDL or 'good' cholesterol (59 vs 40%) and elevated triglycerides (73 vs 50%). People with HIV were also significantly more likely to be current or former smokers (70 vs 55%).

Absolute all-cause mortality rates at one and three years after an ACS diagnosis were similar – actually a bit lower – in the HIV-positive group compared with the HIV-negative group: 7.6 vs 9.8% at one year and 16.6 vs 18.6% at three years.

However, after adjusting for confounding factors including age, sex, race, ACS type, blood lipid levels and smoking, the HIV-positive group had a significantly greater hazard of death. Adjusted hazard ratios were 2.2 at one year and 2.5 at three years, or more than twice the risk of death.

Comparing the different CD4 cell levels, absolute three-year mortality rates were 29.8, 17.9 and 4.9% for HIV-positive people with less than 200 cells/mm³, 200 to 499 cells/mm³ and more than 500 cells/mm³, respectively. After adjusting for confounders, people with 200 to 499 cells/mm³ had a three-year adjusted hazard ratio of 2.5 relative to HIV-negative people – the same as the HIV-positive group as a whole. Those with under 200 cells/mm³ had substantially higher mortality, with an adjusted hazard ratio of 5.6, or more than a five-fold increase. On the other hand, people with CD4 counts above 500 cells/mm³ had a slightly lower risk of death (adjusted hazard ratio 0.7 relative to HIV-negative patients), though this difference was not statistically significant.

Turning to antiretroviral treatment, HIV-positive people who were not on ART had the greatest absolute risk of death at 22.0%, compared with 16.9 and 12.1% for those on protease inhibitor-based and protease-sparing regimens, respectively. Untreated individuals had an adjusted hazard ratio of 3.4 relative to the HIV-negative group, or triple the risk of death. Adjusted hazard ratios for patients taking protease and non-protease regimens were 2.5 and 1.8, respectively, the latter of which was not significantly different from HIV-negative patients. However, when comparing protease-based and protease-sparing regimens directly, the difference in mortality between them did not reach statistical significance.

"HIV patients, in adjusted models, had higher all-cause mortality at one and three years after an ACS hospitalisation," the researchers summarised. There was "no mortality difference at three years for HIV-positive ACS patients with CD4 >500 compared with HIV-negative patients."

As a limitation of their study, they noted that they did not look at cause-specific mortality – so they could not determine how many died of cardiovascular-related causes – and they did not account for treatments such as revascularisation surgery or cardiac medications.

Silverberg explained that it was hard to separate the effects of CD4 cell count and ART use in this analysis, and he said numbers were too small to see if there was a difference in ACS outcomes amongst people who took abacavir (Ziagen), which has been linked to heart attacks in some but not all studies.

"The observed higher mortality after an ACS hospitalization for HIV patients appears to be driven by HIV-related factors, including low CD4 and lack of ART use," the investigators concluded. "These results strengthen recommendations for earlier initiation of ART."

In response to an audience question, however, Silverberg said there were not enough people in the study to address the current controversy as to whether ART use is beneficial amongst those with CD4 cell counts of more than 500 cells/mm³.