Journal of the American Heart Association · Feb 26, 2026

Sex-Difference of Associations Between Cigarette Smoking and Myocardial Fibrosis: The Multi-Ethnic Study of Atherosclerosis

By Akl EW, Zeitoun R, Chehab O et al.

BACKGROUND: Extracellular volume (ECV) and native T1 time (nT1) are markers of interstitial-myocardial-fibrosis by cardiac magnetic resonance and are associated with cardiovascular events, heart failure, and death. However, the association between smoking and interstitial-myocardial-fibrosis at the population level has not been explored. This cross-sectional analysis of the MESA (Multi-Ethnic Study of Atherosclerosis) cohort investigated the relationship between smoking and interstitial-myocardial-fibrosis by cardiac magnetic resonance, as well as the sex differences of this association. METHODS: A total of 2118 participants (53% women) had data on smoking between 2000 and 2012 and ECV (%) and nT1 (ms) at exam 5 (2010-2012). We constructed participant-specific trajectories of average cigarettes per day (ACPD) based on linear interpolation to estimate ACPD between exams 1 through 5 (ACPD₁₋₅). We explored the associations of smoking status at exam 5, ACPD at exam 5, ACPD₁₋₅, and temporal change in smoking status, with ECV and nT1 using multivariable analysis. RESULTS: Current smoking status was associated with increased markers of interstitial-myocardial-fibrosis in women but not in men, ECV% (ꞵ=2% P≤0.001 versus 0.5%; P=0.2) and nT1 (ꞵ=28 ms; P≤0.001 versus 3 ms; P=0.5) in women versus men, respectively. A higher ACPD₁₋₅ was associated with increased ECV% (ꞵ=0.1%; P<0.001) and nT1 (ꞵ=1 ms; P=0.003) in women but not in men. Similarly, higher ACPD at exam 5 was associated with higher ECV% in women versus men. Sex interaction ascertained before stratification was statistically significant. CONCLUSIONS: In this population study, cigarette smoking was associated with a higher prevalence of interstitial-myocardial-fibrosis in women but not in men, indicating differences in the pathophysiology of cardiovascular disease by sex.

doi.org/10.1161/jaha.125.044664Open accessPubMed 41744134Populations