UF Researchers Link Blood Vessel Dysfunction To Poor Prognosis In Women

February 26, 2004

GAINESVILLE, Fla. — Women without obviously obstructed arteries who nonetheless have blood vessels that function abnormally are at increased risk of heart attack, stroke, death and other serious complications, University of Florida cardiologists report in the current issue of Circulation, the journal of the American Heart Association. The same holds true for those with mild forms of heart disease, and, not surprisingly, those with more serious blockages, researchers found.

Previous research conducted predominantly in men found a strong link between changes in how the lining of blood vessel walls reacts to exercise or to the influence of blood flow-regulating chemicals in the body and the development of the artery-clogging process known as atherosclerosis and subsequent heart-related complications. The UF study is the first to extend these findings to a population of women, most of whom did not have severe coronary artery disease, and to associate blood vessel dysfunction with a poor prognosis.

The findings underscore the importance of identifying and eliminating risk factors for heart disease as early as possible, before arteries begin to clog.

“It appears that this is an early marker of atherosclerosis,” said Dr. Richard A. Kerensky, an associate professor of medicine in the division of cardiovascular medicine at UF’s College of Medicine and medical director of the cardiac catheterization laboratory at Shands at UF medical center. “In women with normal or near-normal coronary angiograms, blood vessels that inappropriately constrict when they should dilate indicate risk for cardiac events. We think this is due to damage of the lining of the blood vessel wall that is part of the early process of atherosclerosis. Our findings increase our confidence that this is an important factor in patients at risk for vascular disease.”

The UF study, part of the larger National Institutes of Health-sponsored Women’s Ischemia Syndrome Evaluation, was unique in that it focused solely on women, many of whom had mild coronary artery disease or lacked obviously obstructed arteries. The WISE study seeks to define the prevalence, extent, severity and complexity of heart disease in women and also aims to identify ways to predict heart disease.

In the current analysis, the power of blood vessel dysfunction to predict the likelihood of developing heart problems later persisted even after researchers accounted for factors known to contribute to these adverse events, such as smoking, degree of coronary artery disease, high blood pressure and diabetes.

UF researchers studied 163 women who were experiencing periodic chest pain and who had risk factors associated with atherosclerosis. Study participants underwent coronary angiography. The women were then separated into three groups according to the imaging results. Nearly half had no detectable coronary artery disease, about a third had mild coronary artery disease and the rest had significant coronary artery disease. In three years of follow-up, 43 adverse events were documented. Researchers also used a Doppler-tipped guidewire inserted through a catheter placed in the left main coronary artery to measure coronary artery blood flow and dilation in response to infusions of medications that typically cause blood vessels to widen.

About a third of the women studied died or were hospitalized for heart-related problems during the three-year study follow-up. Researchers noted their arteries were significantly less likely to dilate appropriately in response to some medications used than those who did not develop cardiovascular complications during the study period. In all, women with a normal coronary angiogram and normal blood vessel function fared a lot better than those with a normal coronary angiogram but blood vessel dysfunction.

“Women with (blood vessel) dysfunction were significantly more likely to develop an adverse event than those individuals that didn’t have (blood vessel) dysfunction,” said Dr. Gregory O. von Mering, an assistant professor in the division of cardiovascular medicine at UF’s College of Medicine.

“Heart disease is a major cause of death and morbidity in women,” he added. “Now we have another piece of the puzzle at a very early stage. This raises attention to the need for us to be clued in to this finding that even when there’s only minimal atherosclerosis there may be this additional abnormality in the blood vessels, and that these women are therefore at risk for adverse events.”

Von Mering said future studies will seek to verify the results in a larger analysis and also will assess methods of reversing blood vessel dysfunction to see if associated risks then decline as well.

“Our findings underline the importance of addressing identifiable and treatable risk factors for coronary disease before symptoms occur,” von Mering said. “Women are often less prone to look into these things because they are taking care of their husbands and their children and other people in their lives, but they need to address treatable risks, such as high cholesterol, tobacco use, high blood pressure and obesity, and really focus in on optimizing their health.

“We know by treating risk factors we can impact both established atherosclerosis and (blood vessel) dysfunction,” he added. “It’s really important to think of (blood vessel) dysfunction as on the spectrum of atherosclerotic disease, part of the very early phase of the diseased coronary artery. It’s one of the earliest findings that persists and gets worse obviously as atherosclerosis develops. We don’t recommend people go out and see if they have (blood vessel) dysfunction. What they need to do is identify the risk factors they have with the assistance of their physicians and treat those aggressively.”

The UF study was the first to focus on women presenting with chest pain syndrome who end up in the catheterization lab and are told they have normal or near-normal coronary arteries, said Dr. Arshed Quyyumi, a professor of medicine at Emory University’s School of Medicine.

“The findings show that women with this kind of angiogram and endothelial dysfunction are still at significant risk of adverse outcome or rehospitalization, and this cannot be predicted by their usual risk factors,” Quyyumi said. “Instead of saying ‘you have no blockages’ and ‘everything is fine,’ the doctor may now choose to do this kind of testing and provide some idea of future outlook. However, such a recommendation will require larger confirmatory trials. Finally, we need studies to determine whether treatment of vascular dysfunction will normalize risk.”