Higher cholesterol levels in patients with chronic heart failure are associated with higher survival rates, according to an article in the December 3rd issue of the Journal of the American College of Cardiology. The new findings support results found in earlier studies, but many questions about the nature of the association remain.

"In this study of 417 patients with chronic heart failure, we found that increasing cholesterol was associated with increased survival. This was quite a striking result," said Andrew L. Clark, MD, who led the British-German team. "On the face of it, the result seems quite surprising, given the strong association between cholesterol and vascular disease. However, we have been developing for some time the notion that heart failure is a metabolically stressful illness. In this light, a high cholesterol level can be seen as beneficial as it indicates a greater reserve to deal with metabolic stress. This fits with other studies we have conducted showing a greater survival with increasing body weight in heart failure and following heart surgery."

The study involved two stages. The first stage investigated the association between cholesterol levels and mortality in 114 patients with chronic heart failure who were recruited at a British specialty clinic. The association between lower cholesterol and higher mortality was then validated in a second group of 303 heart failure patients who had their cholesterol levels measured as part of their routine care.

The probability of survival rose 25 percent for each mmol/L (about 39 mg/dL) increase in total cholesterol. On average, patients with a total cholesterol level of 6 mmol/L (about 232 mg/dL) had a 25 percent higher survival rate than patients with a total cholesterol level of 5 mmol/L (about 193 mg/dL).

The authors noted hypotheses that may explain the paradoxical
relationship between cholesterol levels and death rates. "Lipoproteins are good at absorbing bacterial endotoxin. An intriguing notion is that the reason for the immune system activation seen in heart failure patients is related to bowel wall edema allowing bacterial translocation into the body. It may be that lipoproteins mediate a beneficial effect by mopping up any bacterial proteins before they cause immune system activation," Clark said.

Clark emphasized that the observational study cannot establish that low cholesterol is the cause of increased mortality. He noted that a cholesterol level may be a marker of some other factor, and he urged caution in interpreting the findings.

The study involved two stages. The first stage investigated the association between cholesterol levels and mortality in 114 patients with chronic heart failure who were recruited at a British cardiology clinic. The association between lower cholesterol and higher mortality was then validated in a second group of 303 heart failure patients who had their cholesterol levels measured as part of their routine care.

The researchers called for controlled trials of statin drugs in this patient population: "Some work now suggests that statin therapy might be helpful in heart failure independent of cholesterol (increasing cholesterol is still related to improved survival)."

In an editorial, American cardiologists Gregg C. Fonarow, MD, and Tamara B. Horwich, MD, wrote that the current study adds significantly to the growing body of literature on the topic. The researchers first reported a link between lower cholesterol and higher mortality of heart failure in 1998. They recently reported a larger study that linked lower cholesterol with other characteristics known to predict worse outcomes in heart failure.

"The report provides further evidence that the classical relationship seen in the general population and patients with coronary artery disease between higher cholesterol levels and a greater risk of mortality does not hold true in patients with heart failure. This is a surprising and counterintuitive finding," Fonarow said. "Despite this paradoxical relationship between cholesterol levels and survival in heart failure, cholesterol-lowering statin medications may still be beneficial in patients with heart failure. Ongoing clinical trials with statins in patients with heart failure will help to further define the observations made in the study."