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In a large Finnish study of twins, smoking is linked to bleeding in the brain

Researchers at the University of Helsinki in Finland have found a clear link between smoking and subarachnoid haemorrhage, a type of bleeding stroke, in a study of more than 16,000 pairs of twins over 42 years. The study was published last week in the journal Stroke.

The researchers found that bleeding in the brain can be explained to a greater degree by environmental risk factors, such as smoking, than by genetic influence, according to materials produced by the American Heart Association and published in ScienceDaily on 17 September 2020.

An investigation of the Finnish Twin Cohort reaffirmed a link between smoking and subarachnoid haemorrhage or SAH, a type of bleeding stroke that occurs under the membrane that covers the brain and is frequently fatal.

Stroke is a journal of the American Stroke Association, which is a division of the American Heart Association.

In a 2010 study of nearly 80,000 twins from Denmark, Finland and Sweden, results suggested that SAH had more to do with external risk factors and very little to do with genetic influence. Twins share either all or half their genes (identical versus fraternal) so they are valuable for studies designed to evaluate the role of genetics versus environmental factors in disease development.

In this study, researchers sought to clarify the factors involved when only one twin suffered from fatal bleeding in the brain and hypothesised that smoking – the most important environmental risk factor – could play a significant role.

The study utilised health care data from the Finnish Twin Cohort, a national database of 32,564 individuals (16,282 same-sex, twin pairs in Finland) who were born before 1958 and alive in 1974, and followed for over 42 years between 1976 and 2018.

Researchers identified 120 fatal bleeding stroke events among the twins, and the strongest link for a fatal brain bleed was found among smokers.

"Our study provides further evidence about the link between smoking and bleeding in the brain," said corresponding researcher Ilari Rautalin, a sixth-year medical and PhD student at the University of Helsinki.

Data collected from surveys included smoking; high blood pressure (diagnosis or use of antihypertensive medications); physical activity; body mass index; education; and alcohol use. Participants were separated into two groups: smokers (occasional or current) or non-smokers (never and former). Current smokers were classified according to the number of cigarettes smoked per day: light, less than 10; moderate, 10-19; heavy, 20 or more.

The analysis of the 120 fatal bleeding events found:

  • Four fatalities occurred among both twins in two pairs. In the remaining 116 fatalities, one twin died of bleeding in the brain, while the other died of another cause, migrated during the follow-up or was still alive at the end of the study follow-up.
  • Heavy and moderate smokers had three times the risk of fatal bleeding in the brain, while light smokers had slightly less at 2.8 times the risk.
  • Median age at the fatal brain bleed was 61.4 years.

Risk factors such as high blood pressure, lower physical activity rates and being female were not found to be significant influences in this investigation, unlike prior studies. Smoking was associated with fatal bleeding in the brain consistently in both men and women and with bleeding stroke deaths within twin pairs where only one of the twins died from a SAH.

The current study did not have data on non-fatal SAH events and researchers were not able to estimate the impact of former smoking on these brain bleeds. Former smokers and never smokers were combined in the non-smoking category. Researchers were also not able to confirm the aneurysmal origin of SAHs (no patient data was available) and may have included a few non-aneurysmal SAH events.

"This long-term study in twins helps to confirm the link between subarachnoid hemorrhage and smoking," said Rose Marie Robertson, the American Heart Association's deputy chief science and medical officer and co-director of the AHA Tobacco Center for Regulatory Science, who was not involved in the study.

"Not smoking or quitting if you've already started, is an essential component of primary prevention."


Smoking Causes Fatal Subarachnoid Hemorrhage: A case-control study of Finnish twins

The journal Stroke. Published on 17 September 2020.


Ilari Rautalin, Miikka Korja and Jaakko Kaprio.

The first two authors are from the Department of Neurosurgery at the University of Helsinki and the third author is from the Institute for Molecular Medicine Finland FIMM at the University of Helsinki.


Background and purpose

One of the largest twin studies to date suggested that subarachnoid hemorrhage (SAH) is mainly of nongenetic origin, but the causal effect of environmental factors on SAH is yet unknown. We hypothesised that if only one of the twins experience fatal SAH, they do not share the most important environmental risk factor for SAH, namely smoking. If true, such finding would suggest that smoking causes SAH.


Through the nationwide cause-of-death register, we followed 16,282 same-sex twin pairs of Finnish origin from the older Finnish Twin Cohort between 1976 and 2018 and identified all participants who died from SAH. For the baseline, we collected risk factor information about smoking, hypertension, physical activity, body mass index, alcohol consumption and education.

We classified the pairs as monozygotic, dizygotic, or of unknown zygosity. We examined the within-pair risk factor differences in the pairs discordant for SAH, that is, where one twin died from SAH and the other did not. We computed both individual (whole cohort) and pairwise (discordant pair) hazard ratios and 95% CIs.


During the 869,469 person-years of follow-up, we identified 116 discordant and 2 concordant (both died from SAH) twin pairs for fatal SAH. Overall, 25 of the discordant twin pairs were monozygotic. For the whole cohort, smoking (occasional/current) was associated with increased risk of SAH death (hazard ratio, 3.33 [CI, 2.24–4.95]) as compared with non-smokers (never/former).

In the pairwise analyses for discordant twin pairs, we found that the twin who smoked had an increased risk of fatal SAH (hazard ratio, 6.33 [CI, 1.87–21.4]) as compared with the nonsmoking twin. The association remained consistent regardless of the twin pairs’ zygosity or sex.


Our results provide strong evidence for a causal, rather than associative, role of smoking in SAH.


[link url="https://www.sciencedaily.com/releases/2020/09/200917084557.htm"]Smoking linked to bleeding in the brain in large, long-term study of twins[/link]


[link url="https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031231"]Smoking Causes Fatal Subarachnoid Hemorrhage[/link]


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