Association of Cardiovascular Risk Factors With Cardiac Events and Survival Outcomes Among Patients With Breast Cancer Enrolled in SWOG Clinical Trials

Abstract

Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.

Fig 1.

Forest plot of survival by baseline comorbidity status. BL, baseline; CAD, coronary artery disease or ischemic heart disease; CVD-RF, cardiovascular-disease risk factor.

Fig 2.

Cumulative incidence of cardiac events by statistically significant baseline cardiovascular (CV) disease risk factors. CAD, coronary artery disease or ischemic heart disease.

Fig 3.

Cumulative incidence of cardiac events by number of cardiovascular disease risk factors: (A) adjuvant studies and (B) advanced studies.

Fig A1.

Flow diagram showing sample sizes and exclusions. DOB, date of birth.

Fig A2.

Overall survival for patients with versus without a Medicare linkage among patients with ≥ 12 months of continuous baseline Medicare coverage and ≥ 66 years old: (A) diabetes, (B) hypertension, (C) coronary artery disease or ischemic heart disease (CAD), and (D) number of cardiovascular risk factors.