Sex-specific distribution and prognostic relevance of the P-wave Axis in a population-based cohort

Background Abnormal P-wave axis (PWA) reflects atrial conduction disturbances and has been associated with stroke, atrial fibrillation, and premature mortality. Comprehensive population-based data on sex-specific distributions and their prognostic significance remain limited. Purpose To characterize sex-specific distributions of PWA in a large community-based cohort and to evaluate their prognostic relevance. Methods We analysed 16,411 participants aged 45–74 years from the general population with follow-up through May 2023. Participants in sinus rhythm were included. PWA was divided into three subgroups: low (<0°), normal (0-75°) and high (>75°). The primary endpoint was a composite of all-cause mortality or major adverse cardiovascular events (MACE). Associations with baseline characteristics were assessed using Hodges–Lehmann estimator and modified Wilson–Newcombe approach. Kaplan–Meier methods were used to estimate the cumulative probability of MACE or all-cause mortality, overall and stratified by sex; associations were evaluated using Cox proportional hazard models. Results Of 16,411 participants, 14,089 (49.4% women; median age 60 years [interquartile range (IQR) 54–68]; 65 [56–72] and 54 [45–70] for normal, high, and low PWA, respectively) were eligible for analysis. Over a median follow-up of 4.3 years [IQR 3.0–5.8], 679 participants (600 normal, 23 high and 56 low PWA) experienced the composite endpoint of MACE or all-cause mortality, including 265 women and 414 men. In participants without incident MACE, 9,726 had normal, 331 high, and 615 low PWA. Both high and low PWA were associated with older age (+4.9 years, 95% CI 2.1–4.0 and +3.3 years, 95% CI 1.2–2.6, respectively) and higher prevalence of comorbidities, including prior myocardial infarction, heart failure, and pacemaker implantation. Low PWA, compared to normal PWA, was additionally associated with a lower proportion of women (−6.5%, 95% CI 2.4–10.7) and higher rates of coronary artery disease and cardiovascular risk factors, including dyslipidaemia, hypertension, diabetes mellitus, and elevated body mass index (+0.7 kg/m², 95% CI 0.37–0.97) (Table 1). In cumulative incidence analyses, both high and low PWA did not show a significant association with the composite endpoint in women (Figure 1A), whereas low PWA was associated with MACE or all-cause mortality in men (HR 1.46, 95% CI 1.07–2.00, p=0.018) (Figure 1B). Conclusion In this large, population-based cohort, both high and low PWA were associated with older age and a greater burden of comorbidities. Low PWA was additionally associated with an adverse cardiovascular risk profile and the composite endpoint of MACE or all-cause mortality in men. PWA might serve as a sex-specific marker for cardiovascular risk stratification. Further studies are warranted to clarify whether PWA provides independent prognostic value across age groups and in high-risk populations.