Protease inhibitor treatment may be associated with a higher risk of coronary artery calcification, according to a study published this month in the American Heart Journal.
Coronary artery calcification is a more direct measure of the development of atherosclerosis (heart disease) than increases in cholesterol or triglycerides. Calcification occurs when calcium is deposited in plaques, which are accumulations of cholesterol and other debris which narrow or `fur up` arteries, reducing blood flow. The rupture of unstable plaques can cause blood clots or thromboses which are life-threatening.
The degree of coronary calcification has been found to predict the risk of subsequent cardiovascular events in individuals with other risk factors. In this study, of 98 African Americans receiving treatment in Baltimore, participants had relatively low CAC scores, even in the protease inhibitor group, and relatively low total cholesterol levels (4.8mmol/L). However, people in the PI group (n=55) had fivefold higher CAC scores compared to the non-PI group (n=43) (11 vs 1.7).
The participants were largely drawn from a cohort recruited to study the effects of HIV infection and cocaine use on the development of atherosclerosis, itself a sub-study of the large ALIVE cohort. Protease inhibitor recipients were, in the main, taking either ritonavir or indinavir with two nucleoside analogues, whilst the non-PI group were receiving treatment with either dual nucleoside combinations or NNRTI-containing combinations. PI recipients had been taking these medications for an average of 30 months.
The two groups were evenly matched for family history of coronary artery disease, blood pressure, drug and alcohol use, age, sex and body mass index. The study excluded individuals with diagnosed heart disease, high blood pressure, diabetes, and those who smoked more than one packet of cigarettes a day. PI recipients had significantly higher total cholesterol and LDL cholesterol, and significantly more of the PI recipients had total cholesterol and LDL cholesterol above the normal level. These levels were found to be associated with duration of PI treatment by regression analysis.
Earlier this year a sub-study of the Framingham Heart Study found that people with higher coronary calcification scores and higher levels of C-reactive protein (a marker of inflammation) had a higher subsequent risk of heart disease. A
second report, from UCLA, showed that both markers were independent predictors.
In this study, C-reactive protein levels were not elevated in the protease inhibitor group when compared to the non-PI group. The authors suggest that this finding “raises the possibility that PI-linked cardiac disorders, unlikely HIV-1 linked, may not be associated with an inflammatory process”.
The study also found that erythrocyte volume was increased in PI-treated individuals, in the absence of evidence of anaemia.
Meng Q et al. Coronary artery calcification, atherogenic lipid changes, and increased erythrocyte volume in black injection drug users infected with human immunodeficiency virus-1 treated with protease inhibitors. American Heart Journal 144 (4): 642-48, 2002.
Wang TJ et al. C-reactive protein is associated with subclinical epicardial coronary calcification in men and women. Circulation 106:1189-1191, 2002.