Body Composition, Coronary Microvascular Dysfunction, and Future Risk of Cardiovascular Events Including Heart Failure.

Background: Body mass index (BMI) is a controversial marker of cardiovascular prognosis, especially in women. Coronary microvascular dysfunction (CMD) is prevalent in obese patients and a better discriminator of risk than BMI, but its association with body composition is unknown.
Objectives: The authors used a deep learning model for body composition analysis to investigate the relationship between CMD, skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), and their contribution to adverse outcomes in patients referred for evaluation of coronary artery disease.
Methods: Consecutive patients (n = 400) with normal perfusion and preserved left ventricular ejection fraction on cardiac stress positron emission tomography were followed (median, 6.0 years) for major adverse events, including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was quantified as stress/rest myocardial blood flow from positron emission tomography. SM, SAT, and VAT cross-sectional areas were extracted from abdominal computed tomography at the third lumbar vertebra using a validated automated algorithm.
Results: Median age was 63, 71% were female, 50% non-White, and 50% obese. Compared with the nonobese, patients with obesity (BMI: 30.0-68.4 kg/m ² ) had higher SAT, VAT, and SM, and lower CFR (all P < 0.001). In adjusted analyses, decreased SM but not increased SAT or VAT was significantly associated with CMD (CFR <2; OR: 1.38; 95% CI: 1.08-1.75 per -10 cm ² /m ² SM index; P < 0.01). Both lower CFR and SM, but not higher SAT or VAT, were independently associated with adverse events (HR: 1.83; 95% CI: 1.25-2.68 per -1 U CFR and HR: 1.53; 95% CI: 1.20-1.96 per -10 cm ² /m ² SM index, respectively; P < 0.002 for both), especially heart failure hospitalization (HR: 2.36; 95% CI: 1.31-4.24 per -1 U CFR and HR: 1.87; 95% CI: 1.30-2.69 per -10 cm ² /m ² SM index; P < 0.004 for both). There was a significant interaction between CFR and SM (adjusted P = 0.026), such that patients with CMD and sarcopenia demonstrated the highest rate of adverse events, especially among young, female, and obese patients (all P < 0.005).
Conclusions: In a predominantly female cohort of patients without flow-limiting coronary artery disease, deficient muscularity, not excess adiposity, was independently associated with CMD and future adverse outcomes, especially heart failure. In patients with suspected ischemia and no obstructive coronary artery disease, characterization of lean body mass and coronary microvascular function may help to distinguish obese phenotypes at risk for cardiovascular events.
Competing Interests: Funding Support and Author Disclosures This research was supported by a Lemann Cardiovascular Research Fellowship (Dr Souza); the National Institutes of Health (NIH) (U01CA320272, U01CA200468, and U10CA180821), the Lustgarten Foundation Dedicated Lab at Dana-Farber Cancer Institute, the Lustgarten Foundation and Stand Up To Cancer Pancreatic Cancer Collaborative, and the Hale Family Center for Pancreatic Cancer Research at Dana-Farber (Dr Rosenthal); a joint KL2/Catalyst Medical Research Investigator Training (CMeRIT) award from Harvard Catalyst and the Boston Claude D. Pepper Older Americans Independence Center (5P30AG031679-10) (Dr Divakaran); NIH K23HL151909 (Dr Osborne); and the Gilead Sciences Research Scholars Program in Cardiovascular Disease and NIH K23HL135438 (Dr Taqueti). Dr Blankenstein has received research support from Amgen Inc and Novartis Inc. Dr Osborne has received consulting fees from WCG Intrinsic Imaging for unrelated work. Dr Dorbala has received research grants from Pfizer, Attralus, and GE Healthcare; and consulting fees from Janssen, Pfizer, and GE Healthcare. Dr Di Carli has received research grants from Gilead Sciences and Spectrum Dynamics, and consulting fees from Bayer and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)