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Am Fam Physician. 2004;70(4):765-766

Cholesterol levels have been identified as a major risk factor for the development of coronary heart disease (CHD). This has led to multiple studies that have demonstrated the positive impact of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on patients with CHD. Patients with CHD are at risk of developing chronic heart failure (CHF). One recent study showed that statin therapy can reduce the risk of the development of new-onset CHF in patients with CHD. However, in theory, statin therapy in patients with established CHF may not be beneficial, and the presence of CHF has resulted in exclusion from the major statin studies. In addition, preliminary studies have suggested that low cholesterol levels may result in an increased mortality rate in patients with CHF. Rauchhaus and associates evaluated the relationship between cholesterol level and survival in patients with CHF.

The study was divided into two parts: a derivation study and a validation study. Investigators in the derivation study recruited patients with CHF who had been diagnosed by established criteria and enrolled them in a metabolic study. The validation study used a second independent population of outpatients with CHF. Patients in the derivation group had a significant metabolic and cardiac assessment at baseline and were followed over time. Serum cholesterol levels were measured in the validation group during their routine care. Follow-up consisted of telephone calls to patients, their physicians, or through an information system. Survival status was determined by obtaining information from a national office of vital statistics. The primary outcome measure was all-cause mortality.

The derivation study involved 114 patients, while the validation study included 303 patients. Survival in the derivation study was 78 percent at 12 months and 56 percent at 36 months. Increased total serum cholesterol levels in this group were predictors of survival independent of CHF etiology, age, left ventricular ejection fraction (LVEF), and exercise capacity. The best predictors for all-cause mortality were total serum cholesterol levels of 200.8 mg per dL (5.2 mmol per L) or less. In the validation study, the one-year survival rate was 88 percent, and the three-year rate was 68 percent. For each mmol per L incremental increase of total cholesterol in this population, there was a 25 percent increase in chance of survival. Lower cholesterol levels actually predicted a worse outcome independent of age, LVEF, New York Heart Association classification, and peak oxygen consumption.

The authors conclude that low cholesterol levels in patients with CHF were associated independently with a worse prognosis. They caution that statin therapy in patients with CHF has not been well studied and that reducing cholesterol levels in these patients may cause more harm than good. They add that statins may have other beneficial effects in patients with CHF, but these effects need to be established through controlled trials.

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