Extremely high levels of lipoprotein (a) may be a new, independent risk factor for cardiovascular events in women, particularly so for women with higher than average levels of low-density lipoprotein cholesterol, according to an article in the September 20 issue of the Journal of the American Medical Association.

Previous studies of lipoprotein(a) have shown contrasting results, leading to disagreement about the clinical utility of routinely measuring lipoprotein(a). There is also poor agreement among lipoprotein(a) levels obtained by different tests.

Jacqueline Suk Danik, MD, MPH, of Brigham and Women's Hospital, Boston, and colleagues conducted a study to determine the association of lipoprotein(a) levels with the incidence of future cardiovascular events, such as nonfatal myocardial infarction, nonfatal stroke, coronary revascularization procedures, and cardiovascular-related death.

The study included 27,791 initially healthy women in the Women's Health Study, enrolled between November 1992 and July 1995 and followed for 10 years. Lipoprotein(a) level was measured at baseline.

During follow-up, there were 899 new cardiovascular events. In analyses controlling for age, smoking, blood pressure, body mass index, total cholesterol, high-density lipoprotein cholesterol, diabetes, hormone use, C-reactive protein (CRP), and randomization treatment groups, women in the highest quintile of lipoprotein(a) were 1.47 times more likely to develop cardiovascular events than women in the lowest quintile.

"In this large prospective cohort study of initially healthy women, extremely high levels of lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, were associated with increased cardiovascular disease risk, particularly in women with high LDL-C levels. This relationship existed independently of traditional risk markers, and CRP. However, these results were driven almost exclusively by extremely elevated lipoprotein(a) levels among those with above median LDL-C levels, with almost no risk gradient in individuals with lower lipoprotein(a) levels, which constituted the majority of individuals screened," the authors wrote.

"While [our results are] of pathophysiological interest, we do not believe our data support generalized screening of lipoprotein(a) in the population as a whole because only extremely high levels were associated with cardiovascular risk. . Determination of lipoprotein(a) levels should thus be reserved for high-risk subsets of the population such as individuals with premature [myocardial infarction] who have otherwise normal risk profiles or are at particularly high risk because of circumstances such as familial hypercholesteremia," the researchers concluded.