Predicting Sudden Cardiac Death in Women with CAD: Are We There Yet?
Abstract & Commentary
By Joseph Varon, MD, FACP, FCCP, FCCM, Dr. Varon is Chief of Critical Care Services, University General Hospital, Clinical Professor of Medicine and Professor of Acute and Continuing Care at University of Texas Health Science Center, Houston, TX, and Clinical Professor of Medicine, University of Texas Medical Branch, Galveston, TX. Dr. Varon receives grant/research support from Baxter and EKR, is a retained consultant for Baxter, and serves on the speakers bureaus for Baxter, EKR, and The Medicines Company.
Synopsis: Sudden cardiac death (SCD) among postmenopausal women with coronary artery disease is common. The presence of congestive heart failure, reduced kidney function, atrial fibrillation, physical inactivity, and diabetes are independent risk factors for SCD. Some of these factors can be modified and SCD can be prevented.
Source: Deo R, et al. Risk factor and prediction modeling for sudden cardiac death in women with coronary artery disease. Arch Intern Med 2011;171:1703-1709.
This study was aimed at evaluating postmenopausal women with established coronary artery disease (CAD) in an attempt to quantify the risk for SCD in this population, and to compare it with risks factors for mortality from other cardiac and noncardiac clinical conditions. This multicenter trial is a subgroup analysis of the Heart and Estrogen/progestin Replacement Study (HERS), a randomized, double-blinded, placebo-controlled trial of the effect of treatment with 0.25 mg of conjugated estrogens plus 2.50 mg of medroxyprogesterone acetate daily vs placebo on the CAD event rate among 2763 postmenopausal women with documented CAD.1 All study participants were postmenopausal women younger than 80 years of age with no prior hysterectomy, and a history of at least one of the following: acute myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary angioplasty, or angiographic narrowing of a coronary artery of more than 50%.
Of the 2763 postmenopausal women with CAD in the HERS study, the average age was 67 years, and the median follow-up was 4.1 years. There were no significant differences in the rates of primary CAD events or secondary cardiovascular events, including SCD, among women assigned to the hormone group as compared with the placebo group. SCD was defined by the investigators as death that occurred within 1 hour of the onset of symptoms.
In this trial, there were 254 cardiac deaths and 246 noncardiac deaths during the follow-up period. SCD made up 54% (136 events) of the cardiac-related deaths, with an annual event rate of 0.79% per year (95% confidence interval, 0.67-0.94). Of note, there were no significant differences in most of the baseline characteristics across the different groups.
Those patients who died of cardiac causes (either SCD or others) had a higher prevalence of congestive heart failure and diabetes, a higher body mass index, diabetes, physical inactivity, and a lower serum low-density lipoprotein level than those who died of noncardiac causes. Myocardial infarction, congestive heart failure, and a low glomerular filtration rate were associated with a 2-fold or higher risk for SCD. The participants with no risk factors had an annualized SCD risk of 0.34% compared with 2.90% for those with at least three risk factors.
Commentary
Sudden cardiac death remains a significant issue across the world, claiming between 350,000-440,000 lives per year in the United States alone.2 Moreover, cardiopulmonary arrest in the context of cardiovascular disease occurs suddenly and in the most cases without signs or symptoms. Therefore, studies aimed to identify predictors for SCD are extremely important.
Prior studies have shown that women have a 10-fold lower risk of SCD.3 Indeed, the annual rate of SCD among women in the HERS study is lower than SCD rates observed in populations with an established cardiomyopathy. Despite these lower rates, a significant group of well-functioning women with CAD remain at risk of SCD.
This well-conducted study is interesting because it shows that congestive heart failure, reduced kidney function, atrial fibrillation, physical inactivity, and diabetes were independent risk factors for SCD in postmenopausal women with CAD. Many of these risk factors can be modified and, hopefully, fatal outcomes prevented.
References
1. Hulley S, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605-613.
2. Varon J, et al. Therapeutic hypothermia: Past, present, and future. Chest 2008;133:1267-1274.
3. Albert CM, et al. Prospective study of sudden cardiac death among women in the United States. Circulation 2003;107:2096-2101.