Metabolic Changes: Concerns About Heart, Circulatory Risks

A May 2 research letter in The Lancet, by AIDS, lipid, and cardiology specialists at Regions Hospital in St. Paul and the University of Minnesota Medical School in Minneapolis, highlighted growing concerns that high cholesterol and other metabolic changes being seen in some HIV patients may be increasing the risk of heart and circulatory disease.1 The letter was prompted by two cases of unusual coronary artery disease in young men being treated with protease inhibitors; there has since been a third case. These incidents led to a chart review of 124 patients on protease inhibitors, which found that 33% of them had high enough lipid (fat) concentrations in their plasma to be referred for treatment, either with diet and exercise or with lipid-lowering drugs.

The Regions Hospital HIV clinic has developed interim recommendations, including getting baseline blood tests before starting protease inhibitors, lifestyle changes such as improved diet and stopping smoking, and treatment when necessary according to the U.S. National Cholesterol Education Program (NCEP) guidelines for lowering cholesterol in patients with heart disease.2

In a phone conversation on May 11, lead author Keith Henry, M.D., explained why this problem may be more important than some have realized:

* Cardiovascular disease usually develops over decades; this is why heart attacks usually happen to people who are older. If this process is accelerated in some HIV patients--either because of the virus, or because of some the drugs used to treat it--damage could be happening now which could show up increasingly over the next few years. The Regions Hospital HIV Clinic has not had any deaths from heart problems yet, but Dr. Henry has heard of cases from other physicians.

* High cholesterol levels may be a bigger problem than widely realized, since in many of these patients the triglycerides are also high, which can prevent the cholesterol from being measured accurately. But the plasma from many patients "looks like thick cream." The abnormal fat which may be contributing to cosmetic changes in some patients is carried through the circulation, with unknown effects on parts of the body which are not seen. And a modest total cholesterol elevation can be worse than it looks, because it often consists of a combination of an increase in LDL cholesterol (the "bad" cholesterol) and a decrease in the HDL cholesterol (the "good" cholesterol).

* Lifestyle problems, including smoking, poor diet, and lack of exercise, are likely to increase the risk further. Many patients are not on good diets, since in the past the goal has been just getting calories in.

* There are interim measures which can be taken now. The Regions Hospital clinic obtains a fasting lipid profile before starting patients on protease inhibitors, and then 3-6 months after. Abnormalities are treated according to the NCEP guidelines--just as the same conditions would be treated in HIV-negative persons with heart disease.


References

1. Henry K, Melroe H, Huebsch J, and others. Severe premature coronary artery disease with protease inhibitors. The Lancet. May 2, 1998; volume 351, page 1328.

2. National Institutes of Health. Cholesterol Lowering in the Patient with Coronary Artery Disease: Physician Monograph--National Cholesterol Education Program. September 1997 (NIH Publication 97-3794). This document is available at:
http://www.nhlbi.nih.gov/