Among 7,191 cardiovascular disease-free adults in the NHANES III cohort followed for a median 13.8 years, each additional ECG marker of atrial cardiopathy (AC) — prolonged P-wave duration ≥120ms, abnormal P-wave axis, or deep terminal negativity in V1 — was associated with a 41% higher stroke mortality risk (HR 1.41, 95% CI 1.13–1.77). Critically, blood pressure category powerfully modified this relationship: in severe hypertension (≥160/100 mmHg), each additional AC marker nearly tripled stroke mortality risk (HR 2.94, 95% CI 1.82–4.75), while stage 1–2 hypertension yielded a more modest elevation (HR 1.39), and normal/elevated BP showed no significant association. The interaction p-value of 0.003 strengthens confidence in this modifying effect.
This preprint, not yet peer-reviewed, adds meaningful granularity to the growing literature linking subclinical atrial dysfunction — a precursor state to atrial fibrillation — with embolic stroke risk. The synergistic hazard between AC burden and severe hypertension likely reflects compounding mechanisms: pressure-driven atrial remodeling accelerates fibrosis and thrombogenesis, amplifying the already-elevated stroke susceptibility that AC markers signal. For clinicians, these findings suggest routine 12-lead ECGs could stratify stroke risk more precisely when interpreted alongside BP status, potentially identifying a high-risk phenotype warranting aggressive hypertension management. Important limitations include observational design precluding causal inference, reliance on single baseline ECG measurements, and 183 total stroke deaths limiting statistical power in subgroup analyses. Replication in larger, prospective cohorts is needed before clinical translation.