Low CD4 cell count increases heart attack risk for people with HIV

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Immunodeficiency is an important risk factor for heart attack in people living with HIV, results of a large US study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes show. People with recent and nadir (lowest-ever) CD4 cell counts below 200 cells/mm3 were significantly more likely to have a heart attack compared to matched controls. But people living with HIV with nadir or recent CD4 cell counts above 500 cells/mm3 were no more likely to have a heart attack than the HIV-negative controls.

“Our results suggest that immunodeficiency is a key MI [myocardial infarction, or heart attack] risk factor,” write the authors. “While we found an increased risk of MI among HIV+ subjects with low CD (e.g. < 200) compared with HIV- subjects, we found no increased risk among HIV+ subjects with recent or nadir CD4 >500 cells/mm3 compared with HIV- subjects.”

Cardiovascular risk is an increasingly important cause of death among people with HIV. A number of reasons are thought to contribute to this elevation in risk, including a high prevalence of traditional risk factors such as smoking, the side-effects of some antiretroviral drugs and the inflammatory effect of HIV itself.



Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 


Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

A team of US investigators wanted to disentangle these factors and see which were increasing the risk of heart attack.

They designed a case controlled study involving people who received care through the Kaiser Permanente California health plan between 1996 and 2009.

The study population comprised 22,081 people living with HIV who were matched with 230,069 HIV-negative individuals of the same sex, age and who also received care at the same treatment centres.

The risk of heart attack was compared between the people with HIV and the controls, and the investigators conducted a series of analyses to identify specific risk factors for heart attack among the people with HIV.

The people with HIV were followed for a mean of 4.5 years and contributed 99,090 person-years for analysis. The mean duration of follow-up for people in the control group was 5.4 years and they provided 1,253,550 person-years. The overwhelming majority of study participants were men (90%) and aged between 30 and 49 years (70%).

There were 283 recorded heart attacks among the people living with HIV, an incidence rate of 283 per 100,000 person-years. A total of 2064 heart attacks were documented in the control patients, an incidence rate of 165 per 100,000 person-years.

In unadjusted analysis, the people with HIV were found to have a 70% increase in the risk of heart attack compared to the controls (RR = 1.7; 95% CI, 1.5-1.9).

The association between HIV and a higher risk of heart attack persisted after the investigators controlled for traditional risk factors and other confounders (aRR = 1.44; 95% CI, 1.27-1.64). People with HIV who were taking antiretroviral therapy were also shown to have a higher heart attack risk than the controls (aRR = 1.5; 95% CI, 1.3-1.7).

The authors then examined the association between immune status and heart attack risk for the people with HIV.

In their adjusted model, people with a current CD4 cell count below 200 cells/mm3 (aRR = 1.76; 95% CI, 1.31-2.37) or a nadir CD4 cell count below this level (aRR = 1.74; 95% CI, 1.47-2.06) had a higher risk of heart attack than the controls.

However, people with current and nadir CD4 cell counts above 500 cells/mm3 had a heart attack risk comparable to that of the control patients.

“That nadir CD4 acts as a risk factor for MIs is biologically plausible since atherosclerosis is considered a consequence of chronic inflammatory processes,” note the investigators.

Traditional risk factors including older age, male sex, smoking, prior diabetes and prior lipid-lowering medication were also independently associated with heart attack risk.

A sub-analysis included people with HIV who had well-documented antiretroviral treatment histories. Its initial results showed that each additional year of therapy with a protease inhibitor increased the risk of heart attack (RR = 1.14; 95% CI, 1.04-1.26). However, this association disappeared in the adjusted model.

The investigators believe their findings “argue for increased efforts to diagnose and treat HIV as early as possible, which if combined with aggressive traditional CVD risk factor management, might result in a similar MI burden as the general population.”


Silverberg MJ et al. Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care. J Acquir Immune Defic Syndr, DOI: 10.1097/QAI000000000000009, 2013.