Poor R-Wave Progression and Long-Term Outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Poor R-wave progression (PRWP) on the 12-lead electrocardiogram has been linked to excess mortality in single-ethnicity cohorts, but its significance in a contemporary, multi-ethnic population without baseline coronary artery disease (CAD) is unknown. We examined the prevalence and prognostic value of isolated PRWP in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: MESA enrolled 6,814 adults aged 45-84 years free of clinical cardiovascular disease. After exclusion of ECGs with pre-excitation, major conduction disturbances, Q-wave criteria for prior infarction, or missing covariates, 6,323 participants (mean age 61.9 ± 10.2 years; 54% women) were analyzed. PRWP was defined as an R-wave 3 mm in lead V3 with R V3 > R V2 and was present in 202 individuals (3.2%). Cox models adjusted for age, sex, race/ethnicity, hypertension, and diabetes assessed associations with all-cause mortality and major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, coronary revascularization, or heart-failure hospitalization). Results: During a median follow-up of 14.1 years (IQR 13.5-14.7), 1,138 deaths and 918 MACE were adjudicated. PRWP was not associated with all-cause mortality in the prespecified model (hazard ratio [HR] 1.31, 95% CI 0.99-1.73; P = 0.059) nor with MACE (HR 1.29, 95% CI 0.93-1.79). Additional adjustment for current smoking and self-reported emphysema, both more common in PRWP, attenuated the mortality HR to 1.19 (95% CI 0.90-1.58) and MACE (HR 1.26, 95% CI 0.91-1.76). Interaction terms revealed no effect modification by sex or race/ethnicity. Conclusion: In a large, multi-ethnic cohort free of clinical CAD, isolated PRWP did not confer independent risk for all-cause death or major cardiovascular events over 14 years. Prior positive studies may reflect populations enriched for overt coronary disease or other high-risk features rather than a direct effect of the ECG pattern itself.