Leptin has been the subject of intense scrutiny since the early 1990s following its discovery. The protein, when given to mice who were genetically predisposed to obesity, caused weight loss by regulating appetite. However, early hopes that leptin could do the same for overweight humans have been dashed, says study author Naveed Sattar, M.D., Ph.D. Overweight and obese people seem to have some sort of resistance to leptin, he explains.
“This is the first evidence that leptin may be an independent risk factor for the development of coronary heart disease,” says Sattar, senior lecturer in endocrinology and metabolism and an honorary consultant in clinical biochemistry at Glasgow Royal Infirmary in Scotland. “Leptin appears to be as strong a predictor as some well-recognized risk factors such as high systolic blood pressure or low levels of high-density lipoprotein (HDL) cholesterol.”
He cautions that these results must be confirmed by other studies before recommending routine leptin testing.
“Leptin is such a brilliant blood marker for body fat for people at any weight and it is not difficult to measure,” he says.
Sattar’s study used frozen blood samples from the 1989 landmark West of Scotland Coronary Prevention Study (WOSCOPS), a prospective trial that showed that pravastatin, a cholesterol-lowering statin drug, could prevent coronary disease in people with no previous history of it. The current research compared 377 men from the original study who had heart attacks or procedures to open clogged arteries during five years of follow-up and 783 controls who remained free of heart disease events. The controls were matched to cases on the basis of age and smoking history.
The researchers found that leptin levels in the men with heart disease were 16 percent higher than in controls. When they looked at risk of cardiovascular events, Sattar’s team found a 25 percent increased risk for every 30 percent rise in leptin levels, an amount identified in the article as one standard deviation.
The researchers report that leptin remained a risk factor independent of body mass index (BMI), a commonly used way to determine if someone is overweight (BMI of 25 or higher) or obese (BMI of 30 or greater). In addition, leptin levels increased along with levels of C-reactive protein (CRP) – a marker for inflammation in the body that is strongly associated with the development of heart disease. However, when the two proteins were studied together, leptin was still a significant marker for heart disease.
Regarding the BMI findings, he explains that leptin is a better indication of fat mass, since people can have the same body mass index but have different amounts of fat in their bodies. 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, says Sattar.
“Leptin may give important information about the development of heart and blood vessel disease,” he says. “Perhaps because it is a good indicator of the amount of body fat a person has or an independent correlate of insulin resistance, since both leptin and CRP levels increase along with that condition.” Insulin resistance is a condition in which the body makes adequate amounts of insulin but the cells are resistant to using it efficiently.
“Our findings could also point toward some new way in which fat tissue promotes cardiovascular disease,” he says. Sattar notes that regular exercise can have immediate effects on leptin levels because it reduces the body’s fat content, even in the absence of weight loss.
Co-authors include: A. Michael Wallace, Ph.D.; Alex D. McMahon, Ph.D.; Chris J. Packard, D.Sc.; Anne Kelly, MIBiol; James Shepherd, Ph.D.; and Allan Gaw, M.D.
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