Feb. 28, 2002 DALLAS, Feb. 26 – Measuring levels of a molecule that precedes insulin formation appears to be an accurate way to predict heart disease risk in men and women, according to a report in today’s online issue of Circulation: Journal of the American Heart Association.
The molecule is called proinsulin. Researchers found that an elevated level of proinsulin, but not insulin, was associated with about a two-fold increased risk of heart disease in nondiabetic men and women who had suspected but unconfirmed blockages in their coronary blood vessels. This association was stronger in older people.
“We found that proinsulin was a better predictor of coronary heart disease than insulin was,” says Jee-Young Oh, M.D., who conducted the research while completing a fellowship at the University of California, San Diego. “Measurement of proinsulin might help identify patients who have coronary disease and maybe those who are at high risk for developing coronary disease.” Additional studies are needed to clarify the insulin findings, as well as the factors involved in the association between proinsulin and heart disease, Oh and her colleagues conclude.
After laboratory tests for proinsulin became available in the early 1990s, several research groups reported that proinsulin was a better predictor of heart disease risk than insulin. However, potential differences between men and women had not been studied, Oh notes.
Proinsulin is one of several molecules involved in the formation of insulin in the body that appears to impair blood clotting. Increased levels of insulin and proinsulin have been associated with coronary heart disease risk factors such as high blood pressure, high cholesterol levels and obesity. High insulin levels have been identified as a coronary disease marker in men. To evaluate proinsulin’s accuracy as a marker for coronary disease, researchers evaluated laboratory data on 1,456 middle-aged and elderly white people enrolled in the Rancho Bernardo (Calif.) Heart and Chronic Disease Study. The group comprised 554 men and 902 women aged 50 to 97 years. All were tested to confirm that they were not diabetic. Researchers measured insulin, proinsulin and C-peptide, a byproduct of insulin production in blood samples taken from the participants. Oh noted that some evidence has indicated that C-peptide also might be a more accurate predictor of heart attack risk than insulin. Researchers obtained medical histories and conducted electrocardiograms – which evaluate the heart’s electrical activity – for all participants.
They found that about a fourth of the Rancho Bernardo group had coronary heart disease, equally distributed among men and women. Individuals with coronary heart disease had significantly higher proinsulin levels compared to people without coronary disease, and the difference was apparent in men and women.
Rising proinsulin levels more than doubled the likelihood of coronary heart disease in men, and the risk was slightly less than double in women. The association remained significant after the investigators accounted for the effects of a variety of coronary disease risk factors, including age, body mass index (a measure of obesity), blood pressure, and levels of high-density cholesterol (HDL – the good cholesterol that lowers heart disease risk). In contrast, levels of insulin and C-peptide predicted an increased likelihood of coronary heart disease in women but not men.
“These results should be confirmed in other studies, but they are compatible with results of studies that did not evaluate gender differences,” says Oh, who currently is on the faculty at Ewha Woman’s University in Seoul, Korea. “Our findings suggest that proinsulin may be useful for diagnosing coronary heart disease in men and women.”
The contradictory findings related to insulin’s ability to predict coronary disease in men and women also require further investigation, she added.
Co-authors were Elizabeth Barrett-Connor, M.D., and Nicole M. Wedick. The research was funded in part by the National Institute of Diabetes and Digestive and Kidney Disease and National Institute on Aging.
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