A hormone secreted by fat cells may be key in determining heart disease risk -- possibly even as important as blood pressure and cholesterol levels.

Blood levels of the hormone leptin were 16% higher in men with a history of heart disease, compared with healthy men.

And for every 30% increase in leptin levels, the risk of having a heart attack or another cardiovascular "event" rose by 25%.

The association between leptin and heart disease remained regardless of a person's body mass index (BMI), suggesting that leptin is a reliable marker of the amount of fat in the body.

The implication is that the make-up of the body, in terms of how much is fat tissue against muscle may be a better indicator of risk for heart disease than overall obesity, as measured by BMI.

Leptin levels were found to rise in tandem with levels of C-reactive protein (CRP), a marker of blood vessel inflammation and heart disease risk. But the hormone was also independently linked to a person's risk of having a heart attack -- a finding that supports the theory that CRP levels are in part determined by body fat.

The finding that leptin, a fat protein, is linked to heart disease risk independently from CRP, an inflammation marker, strongly suggests that fat may be important in heart disease risk.

Leptin plays a key role in appetite regulation and weight control by telling the brain when the body is full. The discovery of the hormone in the last decade raised hopes that it could be used as a drug to treat obesity.

However, most obese people were later found to have elevated levels of the hormone and thus cannot be helped by injections of the hormone. People who are insulin-resistant, a condition that typically signals the onset of type 2 diabetes, have also been shown to have elevated leptin levels regardless of their body fat.

While the new findings need to be confirmed in other groups before leptin is routinely measured along with cholesterol and blood pressure as part of a heart disease risk assessment, they point to a previously unknown mechanism by which fat leads to heart disease.

Diet and exercise have been shown to reduce leptin levels regardless of weight loss. Therefore, the findings underscore the importance of these lifestyle factors in the development of heart disease.

Circulation December 18/25, 2001;104