P-wave indices and atrial fibrillation: Cross-cohort assessments from the Framingham Heart Study (FHS) and Atherosclerosis Risk in Communities (ARIC) study

Background Atrial fibrillation (AF) is associated with increased morbidity. P-wave indices (PWIs) measure atrial electrical function and are associated with AF. Study of PWI has been limited to single-cohort investigations, and their contributions to risk enhancement are unknown. Methods We examined PWI from the FHS and ARIC study. We calculated 10-year AF risk using adjusted Cox models. We conducted cross-cohort meta-analyses for the PWI estimates and assessed their contributions to risk discrimination (c statistic), net reclassification index, and integrated discrimination improvement. Results After exclusions, the analysis included 3,110 FHS (62.6 +/- 9.8 years, 56.9% women) and 8,254 ARIC participants (62.3 +/- 5.6 years, 57.3% women, 20.3% black race). Over 10 years, 217 FHS and 458 ARIC participants developed AF. In meta-analysis, P-wave duration >120 milliseconds was significantly associated with AF (hazard ratio 1.55, 95% CI 1.29-1.85) compared with <= 120 milliseconds. P-wave area was marginally but not significantly related to AF (hazard ratio 1.31, 95% CI 0.95-1.80). P-wave terminal force was strongly associated with AF in ARIC but not FHS. P-wave indices had a limited contribution toward predictive risk beyond traditional risk factors and markers. Conclusions P-wave indices are intermediate phenotypes for AF. They are associated with AF in cross-cohort meta-analyses but contribute minimally toward enhancing risk prediction.