Sudden cardiac death is a significant contributor to mortality in women, regardless of presence of coronary artery disease (CAD), according to a six-year study published in the Journal of the American Heart Association.

Lead researcher Puja K. Mehta, MD, and her team analyzed 904 women with suspected ischemic heart disease (IHD) with preserved ejection fraction and core laboratory coronary angiography. Mehta and colleagues wrote in their study that while obstructive coronary artery disease (CAD) in women has been linked before to sudden cardiac death (SCD), SCD presents itself more often in women without CAD.

“To our knowledge, incidence of SCD in women with signs and symptoms of IHD without obstructive CAD has not been reported,” they wrote. “New markers and improved models to better predict SCD risk are needed in women.”

Though women represent a slight minority of all SCD cases at 40 percent, the study stated, there are still around 120,000 cases of SCD in American women per year. Traditional IHD risk factors like smoking, hypertension and hyperlipidemia have been associated with SCD in the past but aren’t able to predict mortality on their own; left ventricular ejection fraction can be an indicator, but only in women with “significant” left ventricular dysfunction, which is only a third of the total population affected by SCD.

Mehta and co-authors drew a pool of their more than 900 subjects from the Women’s Ischemia Syndrome Evaluation (WISE) study. Through WISE, the researchers had access to patients’ medical records and were able to observe diagnostic testing and coronary angiographies. Women were divided into three CAD categories: “no CAD” (328 women), “minimal CAD” (223 women) and “obstructive CAD” (353 women). Researchers followed up with the subjects six weeks after testing, and then annually for an average of six years.

The majority of the cohort studied were white women around 58 years old, and more than 75 percent of the population was postmenopausal. In addition to evaluating traditional risk factors of IHD—most women in the study tested positive for three or more—patients were also queried about their history of depression, if they had one.

Ninety-six women died over the course of the study, Mehta and co-authors reported. Of those deaths, 65—68 percent total—were due to cardiovascular causes, while 30 deaths, or 31 percent, were not. One woman’s death couldn’t be classified due to insufficient information. Of the heart disease-related deaths, 48 of 65 could be classified in terms of SCD. Twenty-seven of those 48 women reportedly died of SCD—a 56 percent majority.

According to the study, traditional predictors, higher CAD severity, lower left ventricular ejection fraction and an increasing number of CAD risk factors all predicted cardiovascular events, whether those were SCD-related or not. While older women with higher blood pressure and lower functional capacity were more prone to non-SCD cardiovascular death, the only factor unique to predicting SCD-specific deaths was metabolic syndrome. Longer corrected QT intervals, smoking and a history of depression could also be unique predictors, Mehta and colleagues wrote, though those numbers weren’t statistically significant.

“These results indicate that SCD is a substantial health threat for women independent of angiographic characterization,” Mehta and co-authors wrote. “Notably, the SCD risk variables predict risk across the CAD status, for example, they are not exclusive predictors within the obstructive CAD cohort. Together these results indicate that low angiographic CAD burden in women with evidence of ischemia does not guarantee immunity from cardiovascular death or SCD.”