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

Background: Extracellular volume (ECV) and native T1 time (nT1) are markers of interstitial-myocardial-fibrosis (IMF) by cardiac MRI (CMR) and are associated with CV events, heart failure and death. However, the association between smoking and IMF at the population level has not been explored. Objectives: This study investigated the relationship between smoking and IMF by CMR, as well as the sex differences of this association in the MESA cohort. 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 IMF in women but not in men, ECV% (ꞵ=2% p=<0.001 vs. 0.5%; p=0.2) and nT1 (ꞵ=28ms; p=<0.001 vs. 3ms; p=0.5) in women vs. men, respectively. A higher ACPD1-5 was associated with increased ECV% (ꞵ =0.1%; p<0.001) and nT1 (ꞵ=1ms; p=0.003) in women but not in men. Similarly, higher ACPD at Exam-5 was associated with higher ECV% in women vs. men. Sex interaction ascertained prior to stratification was statistically significant. Conclusion: In this population study, cigarette smoking was associated with a higher prevalence of IMF in females but not in males, indicating differences in the pathophysiology of CVD by sex.