Coronary Blood Flow in Women From the CENTURY Trial: Potential Mechanisms for Sex Differences in Coronary Disease

Despite comparable cardiovascular risk factors, clinically manifest coronary artery disease (CAD) in women is delayed by up to 2 decades compared with men without a defined physiological basis.

This study aims to assess the mechanistic basis of sex differences in CAD using quantitative coronary blood flow (CBF) and coronary flow capacity measured by positron emission tomography in a post hoc analysis of the randomized CENTURY trial.

CENTURY trial data were reanalyzed in 331 women vs 697 men for risk factors, age, quantitative CBF, coronary flow capacity, and clinical outcomes through 14 years of follow-up.

Women and men had similar age, body mass index, hypertension, diabetes, and cumulative summed risk scores. Still, women had less established CAD, lower coronary artery calcium, and fewer positron emission tomography perfusion defects. Women had approximately half the rates of all-cause death (log-rank P = 0.0223), death or myocardial infarction (log-rank P = 0.0138), revascularization (log-rank P = 0.0004), and major adverse cardiac events (log-rank P < 0.0001) compared with men by Kaplan-Meier plots. Rest and stress CBF were 33% higher in women than in men across all comparable strata of age, body mass index, risk factors, and treatment. When integrated with the published reports showing ∼10% smaller coronary arteries in women, these flow data suggest a potential global endothelial shear stress ∼82% higher in women than in men, suggesting a potential hypothetical chronic, diffuse, antiatherogenic differential mechanism.

In the randomized CENTURY trial, women had higher CBF than men across all comparable strata. Combined with the smaller coronary arteries reported in the published reports, this higher CBF suggests a potential, hypothesized higher antiatherogenic ESS that may be a primary, sex-specific physiological mechanism underlying the delayed onset and modifying the course of CAD throughout women's lives. (Comprehensive LifEstyle ModificatioN, Optimal Pharmacological Treatment and Utilizing PET Imaging for Quantifying and Managing Stable CoronaRy ArterY Disease [CENTURY]; NCT00756379).