An investigation of the Finnish Twin Cohort reaffirmed a link between smoking and subarachnoid hemorrhage (SAH), a type of bleeding stroke that occurs under the membrane that covers the brain and is frequently fatal.
The new study by researchers in Finland is published today in Stroke.
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 vs. 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 hypothesized that smoking—the most important environmental risk factor – could play a significant role.
This study utilized 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, B.M., a sixth-year medical and Ph.D. student at the University of Helsinki in Finland.
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 3 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, M.D., FAHA, 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.”
Although cigarette smoking is one of the strongest risk factors for cerebral aneurysm development and rupture, there are limited data evaluating the impact of smoking on outcomes after aneurysmal subarachnoid hemorrhage (SAH).
Additionally, two recent studies suggested that nicotine replacement therapy was associated with improved neurological outcomes among smokers who had sustained an SAH compared with smokers who did not receive nicotine.
METHODS Patients who underwent endovascular or microsurgical repair of a ruptured cerebral aneurysm were extracted from the Nationwide Inpatient Sample (NIS, 2009-2011) and stratified by cigarette smoking. Multivariable logistic regression analyzed in-hospital mortality, complications, tracheostomy or gastrostomy placement, and discharge to institutional care (a nursing or an extended care facility).
Additionally, the composite NIS-SAH outcome measure (based on mortality, tracheostomy or gastrostomy, and discharge disposition) was evaluated, which has been shown to have excellent agreement with a modified Rankin Scale score greater than 3.
Covariates included in regression constructs were patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities (including hypertension, drug and alcohol abuse), the NIS-SAH severity scale (previously validated against the Hunt and Hess grade), treatment modality used for aneurysm repair, and hospital characteristics.
A sensitivity analysis was performed matching smokers to nonsmokers on age, sex, number of comorbidities, and NIS-SAH severity scale score. RESULTS Among the 5784 admissions evaluated, 37.1% (n = 2148) had a diagnosis of tobacco use, of which 31.1% (n = 1800) were current and 6.0% (n = 348) prior tobacco users.
Smokers were significantly younger (mean age 51.4 vs 56.2 years) and had more comorbidities compared with nonsmokers (p < 0.001). There were no significant differences in mortality, total complications, or neurological complications by smoking status.
However, compared with nonsmokers, smokers had significantly decreased adjusted odds of tracheostomy or gastrostomy placement (11.9% vs 22.7%, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51-0.78, p < 0.001), discharge to institutional care (OR 0.71, 95% CI 0.57-0.89, p = 0.002), and a poor outcome (OR 0.65, 95% CI 0.55-0.77, p < 0.001).
Similar statistical associations were noted in the matched-pairs sensitivity analysis and in a subgroup of poor-grade patients (the upper quartile of the NIS-SAH severity scale).
In this nationwide study, smokers experienced SAH at a younger age and had a greater number of comorbidities compared with nonsmokers, highlighting the negative ramifications of cigarette smoking among patients with cerebral aneurysms.
However, smoking was also associated with paradoxical superior outcomes on some measures, and future research to confirm and further understand the basis of this relationship is needed.
More information: Smoking Causes Fatal Subarachnoid Hemorrhage, Stroke (2020). DOI: 10.1161/STROKEAHA.120.031231