Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors

Abstract

Purpose: Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer.

Methods: Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors.

Results: Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]).

Conclusion: Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.

FIG 1.

Specific adipose tissue depots within body mass index (BMI, kg/m²) categories. Both visceral (A) and subcutaneous (B) adiposity increase with BMI. However, visceral adiposity in particular occurs across the BMI spectrum (eg, 2% of normal-weight and 11% of overweight patients in the highest tertile of visceral adiposity). Meanwhile, (C) intramuscular adiposity occurs in substantial numbers of patients in every BMI group (low muscle radiodensity). This novel cardiovascular disease risk factor is occult unless imaging methods such as computed tomography are used.

FIG 2.

Incidence of cardiovascular events in the decade after a diagnosis of nonmetastatic breast cancer. Results from the Breast, Sarcopenia, Cancer and Near-Term Survival study (n = 2, 943). Overall, the cumulative incidence of cardiovascular disease increased steadily, exceeding 15% by year 10 of follow-up (A; cumulative incidence at year 10 = 0.15 [95% CI, 0.14 to 0.17]). Cardiovascular disease incidence was highest for women in the highest tertile of visceral (B; Gray’s test P = .01), subcutaneous (C; Gray’s test P = .01), and intramuscular (D; Gray’s test P ≤ .001) adiposity.