High prevalence of asymptomatic heart disease in HIV-positive patients

Asymptomatic ischaemic heart disease is common in HIV-positive individuals, according to a subanalysis of the SMART treatment interruption study published in the January 11^th edition of AIDS. Using ECG examinations investigators found that approximately 10% of patients enrolled in the study had asymptomatic ischaemic heart disease. Older age, diabetes and high blood pressure were risk factors for the condition.

In HIV-negative patients asymptomatic ischaemic heart disease (reduced blood supply to the heart muscles) is associated with an increased risk of heart attack and death.

An increased risk of heart disease has been identified in HIV-infected patients taking antiretroviral therapy. Longer duration of antiretroviral therapy, particularly if it includes a protease inhibitor, is associated with a particular risk of heart disease.

Anti-HIV therapy can cause levels of blood fats to increase and insulin resistance and it is thought that these side-effects increase the risk of heart attack in antiretroviral-treated patients. However, traditional risk factors for heart disease including older age, male sex, smoking and high blood pressure are also significant.

The SMART study was designed to compare outcomes in HIV-positive patients who took continuous anti-HIV therapy to those who interrupted their therapy when their CD4 cell count was 350 cells/mm³. The study was stopped early when it was found that patients in the intermittent therapy arm were more likely to develop AIDS-defining illness and other serious illnesses, such as heart, liver and kidney disease.

As part of the SMART study patients had an ECG examination. These examinations provided an opportunity for investigators to assess the prevalence and risk factors for asymptomatic ischaemic heart disease in HIV-positive patients. In particular they wished to see if abnormalities detected by the ECG were associated with demographics, HIV disease characteristics, traditional risk factors for heart disease, or with the type or duration of antiretroviral therapy.

Of the 5472 patients enrolled in the SMART study 4831 had ECG readings and were included in the investigators’ analysis. The patients were recruited from over 300 HIV treatment centres in 33 countries. Mean age was 44 years, 28% were female, 30% were black, 40% were smokers, 7% had diabetes, 17% were taking therapy for high blood pressure, and 14% were taking lipid-lowering therapy. Almost all the patients (95%) had experience of antiretroviral therapy, and 89% were taking anti-HIV therapy at baseline. The median duration of anti-HIV treatment was six years.

ECG evidence of asymptomatic ischaemic heart disease was found in 526 patients (10%).

Factors associated with the condition were older age (over 60 years vs. under 40 years: OR 2.2; 95% CI: 1.5 – 3.2, p < 0.001), use of medication to lower blood pressure (OR, 1.5; 95% CI: 1.1 – 1.9, p = 0.003), geographic location (Europe vs. North America, OR, 1.4; 95% CI: 1.1 – 1.7, p = 0.004; Asia vs. North America, OR, 1.6, 95% CI: 1.0 – 2.6, p = 0.05). The investigators were unable to explain the significance of location.

Patients who reported using an NNRTI as part of their antiretroviral therapy appeared to have a lower risk of asymptomatic ischaemic heart disease (p = 0.05), but increasing duration of antiretroviral therapy seemed to attenuate the beneficial effects of NNRTI therapy (as opposed to protease inhibitor therapy), possibly because some NRTI drugs that provide the backbone of anti-HIV therapy can cause metabolic disturbances and therefore increase the risk of heart disease.

Self-reported lipoatrophy was significantly associated with asymptomatic ischaemic heart disease in univariate analysis (OR, 1.3; 95% CI: 1.0 – 1.6, p = 0.03), but not in multivariate analysis.

Diabetes was of borderline significance (OR, 1.4; 95% CI: 1.0 – 2.0, p = 0.06).

Some traditional risk factors for heart disease such as smoking, cholesterol, triglycerides and the use of lipid-lowering drugs were not significantly associated with asymptomatic ischaemic heart disease in this study.

The investigators conclude that ECG evidence shows that there was a high prevalence of asymptomatic ischaemic heart disease in the SMART study population. But they add, “the clinical significance of our data…remain to be determined.” Only when patients are prospectively evaluated will it be possible to say if asymptomatic ischaemic heart disease is predictive of symptomatic heart disease or death in HIV-infected patients in the future.

Nevertheless, given the high prevalence of asymptomatic ischaemic heart disease revealed by their analysis the investigators suggest that patients with the highest risk of this condition – those who are older, or with high blood pressure or diabetes – receive “closer follow-up or more aggressive cardiovascular protective interventions.”