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

Abstract

Objective

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.

Methods

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.

Results

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 ( p = 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 ( p = 0.05).

Conclusions

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.