Sex, Smoking, and Risk for Subarachnoid Hemorrhage

Key points:

    • To examine associations between smoking habits and SAH in a large, population-based, prospective cohort.

    • To assess interaction between smoking habits and sex.

    • To evaluate associations between smoking habits and the risk of sudden deaths from SAH.

    • To evaluate the effect of smoking cessation on risk for future SAH.

According to prospective cohort studies, smoking is the most important risk factor for unruptured intracranial aneurysms, correlating with their appearance, growth and rupture. In addition, earlier studies report that women are at higher risk for SAH with adjusted hazard ratios (HRs) from 1.4 to 1.9 compared with men. In this paper, published August, 2016, on Stroke, Authors analyzed in detail risk factors of aneurysmal subarachnoid hemorrhage (aSAH), using data of the National FINRISK Study, a large Finnish population survey on risk factors of chronic diseases. Follow-up started at the enrollment and ended at the first aSAH, death or on December 31, 2011. Baseline cohort characteristics are reported in the following table.

Baseline characteristics

Participants 65521 (33805 women)
first-ever aSAH 492 (266 women)
Median age 45 y/o
Median follow-up time aSAH 14.8 years
Median follow-up time cohort 21.1 years

Participants, based on smoking status, were divided into 8 categories and at baseline, 19% of women and 38% of men were current smokers.

Smokers categories
  • never-smokers, who reported no smoking at all or <100 cigarettes in their lifetime;
  • occasional smokers, who had smoked on a non-daily basis during the past 6 months before enrollment;
  • former smokers, who had quit >6 months before enrollment;
  • recent quitters, who had quit smoking within 6 months before enrollment;
  • 1-10 CPD (cigarettes per day)
  • 11-20 CPD
  • 21-30 CPD
  • ≥31 CPD

Joni Valdemar Lindbohm et al. found an interesting linear dose-dependent relationship between CPD and risk for SAH and this relation was stronger in women in all groups, indicating multiplicative interaction between sex and CPD. This evidence suggests that female sex may not be an independent risk factor for SAH.

Incidence rates of aSAH

Incidence rates of subarachnoid hemorrhage (SAH) shown by a competing risks model; the y axis describes competing risk rate, and the x axis, age in years. Competing risk rate described by sex and by smoking status; never-smokers (dashdot red), former smokers (dash-dot blue), 1–10 CPD (dash red), 11–20 CPD (dash blue), 21–30 CPD (solid red), and 30< CPD (solid blue). No SAH cases was observed in women smoking >30 CPD.

Moreover, Authors found that all CPD categories elevated the risk of sudden death from SAH more in women than in men.

In conclusion:

  • Smoking is a dose-dependent risk factor for SAH, particularly in women.
  • Even light smoking (1–10 CPD) elevated the risk for SAH and smoking cessation reduces this risk.
  • Risk of aSAH decreases rapidly reaching the risk level of never-smokers within 5 years.
  • It is possible that risk of aSAH is higher in women because smoking reduces estrogen levels, which further leads to collagen depletion, inflammation, and dysfunction of mural cells in vessel walls.

Reference

  • Joni Valdemar Lindbohm, Jaakko Kaprio, Pekka Jousilahti, Veikko Salomaa, Miikka Korja. Sex, Smoking, and Risk for Subarachnoid Hemorrhage. Stroke. 2016 Aug;47(8):1975-81. doi: 10.1161/STROKEAHA.116.012957

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