Detectable viral load and low nadir CD4 cell count increase the risk of heart attack for people with HIV

A detectable viral load, a low nadir CD4 cell count and an elevated CD8 cell count are associated with an increased risk of heart attack for people with HIV, French investigators report in Clinical Infectious Diseases. These virologic and immunologic factors were significant, even after taking into account traditional risks for cardiovascular disease.

“We found that an HIV-1 RNA level > 50 copies/ml, a low CD4 T-cell nadir, and a high current CD8 T-cell count were significantly associated with an increased risk of MI [myocardial infarction],” write the authors.

Cardiovascular disease is an increasingly important cause of serious illness and death in people with HIV. The exact reasons are controversial, but may include traditional risk factors, the side-effects of some antiretroviral drugs, immunodeficiency and the damage caused by uncontrolled HIV replication.

To establish a clearer understanding of the causes, investigators from the French Hospital Database on HIV (FHDH)-ANRS CO4 study designed case-controlled research involving participants who received care between 2000 and 2009.

Cases were HIV-positive people who had experienced a first heart attack. Each was matched with up to five HIV-positive individuals of same gender and age who had not experienced a heart attack. For both cases and controls, information was gathered on possible risk factors for cardiovascular disease, including traditional causes, as well as the use of antiretroviral therapy, viral load and immune status.

Most of the participants were male (89%) and their median age was approximately 46 years. There was a higher prevalence of traditional risk factors for cardiovascular disease among the participants who experienced a heart attack when compared to those who did not have a myocardial infarction. These factors included smoking (p = 0.028), family history (p < 0.001), high blood pressure (p = 0.001), diabetes (= 0.036), use of stimulant drugs (p = 0.041) and elevated cholesterol and triglycerides.

People who experienced a heart attack were more likely to have a detectable viral load than those who remained heart-attack free (57 vs 48%; p = 0.006), had a higher median viral load (127 vs 50 copies/ml; p = 0.002), a lower nadir CD4 cell count (135 vs 177 cells/mm³; p = 0.001) and a higher current CD8 cell count (p < 0.001). Heart attack patients were also more likely to have a history of AIDS-defining illness (44 vs 34%; p = 0.001) and to have had HIV for longer (10 vs 9 years; p = 0.001).

The biggest single risk factor for heart attack was smoking (OR = 4.08; 95% CI, 2.75-6.04). Several other traditional risk factors were also associated with heart attack. These included hypertension (OR = 2.13; 95% CI, 1.34-3.40) and high cholesterol (OR = 2.33; 95% CI, 1.67-3.25).

A number of HIV-related factors were also significant, including cumulative exposure to protease inhibitors. Each ten years of exposure to drugs in this class more than doubled the risk of heart attack (OR = 2.23; 95% CI, 1.17-4.24). No other class of antiretroviral had a significant association with heart attack.

After controlling for traditional factors, the investigators found that a detectable viral load increased the risk of heart attack by approximately 50% (OR  = 1.51; 95% CI, 1.09-2.10). A low nadir CD4 cell count was associated with an increased risk of heart attack; however, current CD4 cell count had no effect on risk. “The CD4 T-cell count nadir may reflect the length of time during which HIV replicated freely, thus damaging the immune system, and has been linked to persistent immune activation even in patients with controlled viral load, which may explain its association with the risk of MI,” comment the authors.

A high current CD8 cell count was also a significant risk factor. Participants with a count above 1150 cells/mm³ were approximately 50% more likely to have a heart attack compared to those with a count below 760 cells/mm³. The investigators stressed the novelty of this finding. 

“In summary, we found that a low CD4 T-cell nadir, a current CD8 T-cell count over 1150 cells/mm³ and a plasma HIV-1 RNA level > 50 copies are independently associated with the risk of MI in HIV-infected individuals,” conclude the authors. They believe their study has immediate implications for HIV treatment and care, commenting: “These findings support early diagnosis and treatment of HIV infection and call for studies of interventions designed to diminish persistent immune activation in patients with uncontrolled viral loads.”

Lany S et al. HIV replication and immune activation are independent predictors of risk of myocardial infarction in HIV infected individuals. Clin Infect Dis, online edition. DOI: 10.1093/cid/cis489, 2012.