Coinfection with hepatitis C virus (HCV) may be associated with an increased risk of cardiovascular events such as heart attacks and strokes, even though people with hepatitis C have lower cholesterol levels, according to a study presented on Thursday at the XVII International AIDS Conference in Mexico City.
Cardiovascular disease has become an increasing concern as people with HIV live longer. Over time, atherosclerosis (“hardening of the arteries”) can lead to heart attacks and strokes as blood flow is restricted to the heart muscle or the brain, respectively. Several studies have shown that HIV-positive people taking antiretroviral therapy are at increased risk of cardiovascular disease, in part due to elevated cholesterol and triglyceride levels.
Research has shown that people with hepatitis C are less likely to have abnormal blood lipid levels, but are more prone to metabolic complications such as insulin resistance and fat accumulation in the liver (steatosis). However, it is not known how hepatitis C coinfection influences lipid levels or other metabolic changes related to HIV infection or its treatment, nor how this might impact the risk of cardiovascular disease.
Roger Bedimo and colleagues from the United States analysed data from the Veterans Administration Clinical Case Registry to look at the impact of HIV/hepatitis C coinfection on risk of acute myocardial infarction (MI) and cerebrovascular disease (stroke) after adjusting for other risk factors. The registry includes more than 20,000 HIV-positive patients, of whom about one-third also havr hepatitis C.
The investigators identified coinfected individuals in the database who had experienced an acute MI or stroke. They then compared the risk of such events in the pre-HAART era (1980 to 1995) and the post-HAART era (1996 to 2004), ie before and after combination therapy was introduced.
Consistent with prior studies, people with hepatitis C were less likely to have abnormally high blood fat levels or to be taking lipid-lowering medications. Over the entire study period, 18% of coinfected patients had total cholesterol above 240 mg/dL, compared with 27% of people with HIV alone (p
Overall, traditional risk factors such as older age, diabetes, and high blood pressure predicted an increased risk of acute MI or stroke with one exception. Strangely, smoking was not associated with an elevated risk of cardiovascular disease—in fact, it had a protective effect with regard to stroke—a finding the researchers were unable to explain.
Before the advent of HAART, HIV/hepatitis C coinfection was associated with about a 40% higher risk of acute MI or cerebrovascular disease. In the HAART era, the rates of acute MI were 3.36 per 1000 person-years for people with HIV alone and 4.19 per 1000/person-years for coinfected people. This represented a 25% increased risk after adjusting for other factors, but failed to reach statistical significance (adjusted HR 1.25; p = 0.072).
For cerebrovascular disease in the HAART era, the corresponding rates were 11.12 and 12.47 per 1000 person-years for HIV monoinfected and HIV/hepatitis C coinfected individuals. In an adjusted analysis, this represented a 20% increased risk, which was statistically significant (adjusted HR 1.20; p = 0.013).
The investigators concluded that HIV/hepatitis C coinfection was an independent risk factor for acute MI and cerebrovascular disease prior to the advent of HAART. After the introduction of effective combination therapy, this effect appears to have declined for acute MI but not for stroke, since coinfection was no longer a significant predictor of acute MI but remained significantly associated with stroke. However, the impact of coinfection on MI risk remained significant for patients over 60 years of age.
Based on these findings, the researchers recommended that “adjustment for HCV status is indicated” when analysing cardiovascular disease risk in people with HIV.