Link between glucose levels and death in patients with cardiovascular disease

Men with cardiovascular disease may be at considerably increased risk for death even when their blood sugar level remains in the "normal" range, suggests a new study by a team of scientists at UCLA and Cedars-Sinai Medical Center in Los Angeles.

The study, a statistical analysis examining the connection between glucose (blood sugar) levels and death in patients with cardiovascular disease, is published in the American Journal of Epidemiology.

Cardiovascular disease includes coronary heart disease, stroke, angina and peripheral vascular disease. Currently, doctors consider a glucose level of 100 or less to be normal, 101-126 to be impaired and above 126 to be diabetic.

"Our findings suggest that for men with cardiovascular disease, there is apparently no 'normal' blood sugar level," said Sidney Port, UCLA professor emeritus of mathematics and statistics, and lead author of the study. "For these men, across the normal range, the lower their blood sugar, the better. Their death rate over a two-year period soars from slightly more than 4 percent at a glucose level of 70 (mg/dl) to more than 12 percent at 100 (mg/dl) -- an enormous increase."

Surprisingly, however, and contrary to conventional belief, above 100 (mg/dl), their risk does not seem to change -- it stays at the same high level -- no matter how high above the normal range, Port said. Their death rate at 100 and 150 is the same. Although these data suggest that blood sugar for men with cardiovascular disease should be as low as possible, co-author Mark Goodarzi, assistant professor-in-residence at Cedars-Sinai Medical Center's Division of Endocrinology, cautions that their study by no means proves that deliberately lowering glucose would reduce mortality.

"Such a fact can be established only by a suitable clinical trial" Goodarzi said.

Currently, no such trials are scheduled.

In another surprising result that Port and his co-authors cannot explain, women with cardiovascular disease show a dramatically different response from men. "For women, we found no evidence of any change in risk across the normal range, from 70 to 100, but then their risk seems to rise quickly through the impaired range and continues to increase with higher glucose in the diabetic range; therefore a blood sugar level of 100 seems to be a sensible cut point for women with cardiovascular disease."

"Why there should be such a profound difference between men and women with respect to how glucose affects mortality in the presence of atherosclerosis is a mystery that needs to be further pursued," Goodarzi said. "To date, we and colleagues we have consulted can offer no explanation."

"These large gender differences may have previously remained undetected because earlier studies looked either at men and women together or a younger, healthier group of men," said Port, whose study analyzed men and women with cardiovascular disease separately. "If you look at men and women combined, you get a highly distorted picture because they respond so differently."

Using extensive heart study data from the town of Framingham, Mass., collected every second year since 1948, Port and his co-authors performed a sophisticated statistical analysis, which made adjustments for factors such as the patients' cholesterol levels, blood pressure, cigarette smoking, body mass index and antihypertensive drug use. The researchers analyzed more than 1,200 people (686 men and 517 women), ages 45 to 74, diagnosed with cardiovascular disease. Because the researchers' statistical technique allowed them to take advantage of the fact that many patients were examined over multiple two-year periods, they report on more than 3,800 observations.

In a follow-up study, they are analyzing whether blood sugar levels are linked with death or development of cardiovascular disease in people who have not been diagnosed with cardiovascular disease.