Accelerated hardening of the arteries in patients with HIV; traditional risks the main cause

Atherosclerosis is accelerated in HIV-positive patients, according to research published in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Investigators monitored hardening of the carotid and coronary artery over a three-year period. Traditional risk factors for cardiovascular disease were the most important predictors of the acceleration of atherosclerosis.

“Carotid and coronary atherosclerosis is accelerated in HIV-infected persons. This increased rate of atherosclerosis was mainly explained by traditional risk factors,” comment the investigators. They suggest “early diagnosis, treatment and control of atherogenic risk profiles might reduce the heightened risk of vascular disease that often accompanies HIV.”

There is now a substantial body of research showing that HIV-positive people have an increased risk of cardiovascular diseases such as heart attack and stroke.

Controversy surrounds the exact causes, but it seems likely they include traditional risk factors, as well as the inflammatory effects of HIV and the side-effects of some antiretroviral drugs.

Monitoring the development of atherosclerosis in the carotid artery (carotid intima-media thickness, or c-IMT) and the coronary artery (coronary artery calcium, or CAC) can help predict a patient’s risk of cardiovascular disease.

Investigators from the CARE sub-study of the Nutrition for Healthy Living study therefore used ultrasounds and CT scans to determine three-year changes in the carotid and coronary arteries of 255 HIV-positive individuals.

The patients had an average age of 45 years at baseline. Just over a quarter were women, approximately 50% were white, and 44% were smokers.

Baseline analysis was conducted between 2002 and 2003. Two measurements of c-IMT were taken (the common and internal). Tests were repeated between 2005 and 2007.

In healthy adults in early middle age, an average common c-IMT is 0.4 mm at birth and 0.7 mm at age 80, and approximately 13% have c-IMT greater than the 75^th percentile. Three-quarters of healthy young middle-aged people have a CAC score of zero.

There was significant evidence of more aggressive hardening of the arteries in the study population.

At baseline, approximately a quarter of patients had common and internal c-IMT scores above the 75^th percentile. After three years, this had increased to 38% for common c-IMT and 30% for internal c-IMT.

The mean common c-IMT progression was 0.016 mm per year; with internal c-IMT increasing by a mean of 0.020 per year.

“The progression of carotid atherosclerosis in our study of 0.016 mm/year appears accelerated. It should be emphasized that these small changes are clinically significant, as a change in IMT thickening of 0.012 mm per year has been shown to result in a 52% change in CV events,” comment the authors.

Yearly progression of c-IMT was significantly higher for men than women (p = 0.03). There was some evidence that progression was faster in patients whose antiretroviral therapy included a protease inhibitor compared to a non-nucleoside reverse transcriptase inhibitor (0.018 vs 0.011), but the difference was not significant.

Progression was not associated with either CD4 cell count or viral load. 

However, traditional risk factors were important. At both baseline and follow-up, the Framingham Risk Score (ten-year risk of heart attack) was significantly higher for those with common and internal c-IMT above the 75^th percentile.

Metabolic syndrome was also significantly more common in patients with baseline evidence of c-IMT than those without.

Further analysis showed that a number of traditional risk factors were significantly associated with progression of c-IMT. These included age, systolic blood pressure, triglycerides, insulin resistance, fasting glucose above 125 mg/dl, use of glucose lowering medication, and smoking.

The investigators then turned their attention to coronary artery calcification. They note: “In the non-HIV population approximately 7% of those over the age of 45 years and without coronary calcium are estimated to develop coronary calcium per year.”

However, a third of the HIV-positive patients “had annual progression of coronary calcium deposits indicating a more rapid progression of coronary atherosclerosis as well in this population”.

Significantly more patients with an intermediate or high Framingham risk score than a low score had CAC progression (42 vs 26%, p = 0.04). Progression was also more common in the over 50s and in men compared to women (31 vs 21%).

No HIV-related factors were associated with hardening of the coronary artery, but traditional factors such as insulin resistance, and triglycerides were significant.

“Both c-IMT and CAC progression rates in HIV-infected patients appear higher than expected in this age group; however traditional CV risk factors remain the strongest determinants of carotid and coronary atherosclerotic disease progression in this population,” comment the investigators.

They note, “aggressive CV risk reduction with lipid-lowering and hypertensive medications appears to be effective at slowing the progression of atherosclerosis in HIV-infected patients.”