Survival bias explains improved survival in smokers and hypertensive individuals after aSAH.

Abstract

Two recent hospital-based studies have reported that both smoking and hypertension-the 2 most important risk factors for aneurysmal subarachnoid hemorrhage (aSAH)-may improve survival after aSAH. We tested the hypothesis that a higher case fatality among smokers and hypertensive individuals after aSAH contributes to these paradoxical findings. We followed 65,521 population-based FINRISK participants during 1.52 million person-years and identified 445 first-ever hospitalized aSAHs and 98 sudden-death aSAHs occurring between 1974 and 2014. We measured risk factors prior to disease onset in the cohort surveys, and confirmed, among all sudden-death aSAHs, 80% by extensive (including the brain) forensic autopsy; the remaining 20% were based on clinical examination (CT of the head, spinal tap, or both). The Cox proportional hazards model estimated survival curves. Analyses repeating the protocol of the 2 recent hospital-based studies again showed improved survival among smokers and those with hypertension. Conversely, in analyses including more accurate risk factor measurements and including patients with sudden-death aSAH who never reached a hospital, these paradoxical results were reversed. Smokers had reduced survival compared to that of never-smokers (<i>p</i> = 0.04), and those with high systolic blood pressure (SBP) (≥160 mm Hg) had reduced survival when compared to survival of those with SBP <160 mm Hg (<i>p</i> = 0.05). After aSAH, smoking and hypertension were associated with worse survival. The earlier and opposite findings are likely explained by inadequate risk factor measurement and by survival bias inherent to hospital-based risk factor studies lacking information on out-of-hospital deaths confirmed by autopsy.