Deepak Gulati, MD
Smoking has been identified as the most important lifestyle risk factor for subarachnoid hemorrhage (SAH) and accounts for at least one third of all cases.
Familial risk is defined as the probability of a healthy family member being affected by the same disease that has already affected at least one other family member. Familial risk of SAH depends on a number of factors, including genetic and environmental factors. It has been a challenge to estimate the genetic risk of SAH in relatives given the relatively low incidence of SAH. The accurate estimation of genetic risk could have significant implications on prophylactic screening protocols of intracranial aneurysms. Large twin cohorts provide a “shortcut” to carry out the estimation of heritability. Twin studies usually provide the natural way to separate familial resemblance from genetic influence. The Nordic Twin Study in 2010 indicated that most twin pairs were discordant for SAH, i.e., only one twin died from SAH. However, the role of risk factors in explaining this discordance was not studied.
The study by Rautalin and co-authors hypothesized that smoking — the most important environmental risk factor for SAH — may be associated with the discordance noticed in the Nordic Twin Study. In this study, most of the cases of fatal SAH were found to be discordant (the co-twin did not die from SAH). Among discordant pairs, 25 were monozygotic, 72 dizygotic, and 19 were of uncertain zygosity. Smoking was found to be associated with increased risk of fatal SAH across 16,282 same-sex Finnish twin pairs irrespective of the twin pair’s sex or zygosity. In addition, smoking predicted SAH death within discordant sibling pairs based on pairwise analyses. The authors found a significant association between strong alcohol consumption and the risk of fatal SAH, but this association was no longer apparent after adjusting for smoking. These findings suggested that smoking may contribute to the familial manifestation of SAH and are consistent with a strong evidence for a causal effect.
Previous studies suggested that smoking is a dose-dependent risk factor for SAH. The authors in this study showed that both heavy (HR 3.01, CI 1.58–5.73) and moderate smokers (HR 3.98, CI 2.44–6.49) had a slightly higher risk than light smokers (HR 2.83, CI 1.64–4.9), but with overlapping confidence intervals.
The authors concluded that smoking increased the risk of fatal SAH, also within twin pairs, and may contribute to a familial manifestation of SAH.
