All Smokers, but Especially Women, at Increased Risk for Subarachnoid Hemorrhage

Deborah Brauser

July 21, 2016

Smoking even 1 to 10 cigarettes per day can lead to twice the risk for subarachnoid hemorrhage (SAH) compared with nonsmokers, and this risk increases as smoking amounts increase — and jumps even more dramatically for women, new research suggests.

A population study of more than 65,000 individuals in Finland showed that, compared with men who did not smoke, men who were light smokers had almost double the risk for SAH, ranging up to almost 3 times the risk for heavy smokers, defined as up to 30 cigarettes per day.

For women, however, light smoking conferred 3 times the SAH risk vs never smokers, ranging up to 8 times the risk for heavy smokers.

"We were a bit surprised that vulnerability to smoking may explain, at least in part, the previously reported increase in SAH risk in women," said lead author Joni Valdemar Lindbohm, MD, Department of Public Health, University of Helsinki, Finland.

Dr Joni Valdemar Lindbohm

In addition, the risk for SAH was significantly lower for the study participants who were former smokers, with hazard ratios (HRs) for the men and for the women not much greater than for the never-smokers.

"There is no safe level of smoking. But the good news is that it's never too late to stop smoking. Doing so can reduce SAH risk in both sexes," Dr Lindbohm told Medscape Medical News. "One of the important take-home messages for patients and physicians is to support smoking cessation programs and legislation."

The findings were published online July 21 in Stroke.

Smokers at Risk

The investigators evaluated data for 65,521 individuals (52% women; mean age, 45.3 years) who participated in the National FINRISK Surveys from 1972 to 2007. The mean follow-up was 21.1 years, or 1.38 million person-years.

Smoking status and socioeconomic data were determined by self-administered questionnaires. Clinical measurements of height, weight, blood pressure, and cholesterol were also performed.

Among the participants, 38% of the men and 19% of the women identified themselves as current smokers at baseline. There were four main smoking categories:

  • Nonsmokers: never smokers or <100 cigarettes over a lifetime

  • Light smokers: 1 to 10 cigarettes/day on average

  • Moderate smokers: 11 to 20 cigarettes/day

  • Heavy smokers: 21 to 30 cigarettes/day

In addition, those who had quit smoking within 6 months of enrollment were considered "recent quitters," and those who quit more than 6 months before were considered "former smokers."

At the end of follow-up, 492 SAHSs had occurred, including in 54% of the women.

For the whole group of current smokers, the HR for an SAH was 2.77 vs nonsmokers (95% confidence interval [CI], 2.22 - 3.46).

For all of the women smokers, the HR for an SAH was 3.43 (95% CI, 2.58 - 4.55) and for the men it was 2.20 (95% CI, 1.56 - 3.10).

"This translates to a population attributable risk estimate of 31% in both men and women," report the researchers.

The risk increased with increasing consumption and was highest in both sexes for heavy smokers, although heavy smoking conferred a much greater risk in women.

Table. Risk for SAH by Smoking Level

Cigarette Consumption HR in Men HR in Women
Light smoking (1 - 10 cigarettes per day) 1.9 3.0
Moderate smoking (11 - 20 cigarettes per day) 2.1 3.9
Heavy smoking (21 - 30 cigarettes per day) 2.8 8.4


Recent vs Former Smokers

Not surprisingly, recent quitters had a higher HR than former smokers (1.93 vs 1.34, respectively). And heavy smokers had a higher HR than light smokers (3.79 vs 2.54).

HRs were also significantly higher for women vs men in all categories (P = .01).

Moreover, "when an adjusted model included interaction terms between sex and cigarettes per day or pack-years, female sex was no longer an independent SAH risk factor," write the investigators.

Study limitations cited included the following: How smoking patterns may have changed after the baseline questionnaires was unknown, alcohol consumption was not included in the final adjusted model, the possible use of hypertension and hypercholesterolemia medications weren't taken into account, and the incidence rate of SAH "is believed to be exceptionally high in Finland."

Nevertheless, "the results emphasize the importance of worldwide smoking cessation agendas and active treatment of nicotine dependence," the researchers summarize.

Dr Lindbohm noted that information on further analyses looking into the generalizability of the study findings are in press.

"Quit to Avoid This Complication"

When asked for comment, Brian Silver, MD, director of the Rhode Island Hospital Stroke Center in Providence and professor of neurology at The Warren Alpert Medical School of Brown University, noted that the findings "were consistent with the knowledge" that smoking increases the risk for SAH.

Dr Brian Silver

"The piece that is novel is that subarachnoid hemorrhage is related to not just cigarette smoking but in a graded fashion to the amount of cigarettes consumed on a daily basis," said Dr Silver, who is also a spokesperson for the American Heart Association.

"There appears to be a pretty good dose-response relationship with subarachnoid hemorrhage, and that relationship is magnified in women," he added.

Dr Silver noted that it was also "pretty significant" that even the light smokers were at such a high risk.

"I think the message is that, as with other health-related effects from smoking, you're better off never having smoked in the first place. But if you do smoke, you should try to quit to try to avoid this complication, as well as many others," he said.

"It's worth noting that most subarachnoid hemorrhage is related to a rupture of an aneurysm. So from a mechanistic standpoint, if you were trying to explain why we're seeing this increase risk with respect to cigarette smoking, it may be because smoking may weaken the walls of the artery in predisposed individuals so that it bulges and can eventually rupture," said Dr Silver.

He added that this may affect the collagen that keeps the vessel wall intact, "making it looser and more vulnerable to rupture." And for women, that effect of weakened collagen might be more pronounced.

The study was funded by the Department of Public Health at the University of Helsinki. Dr Lindbohm, Dr Silver, and all but one of the coauthors have disclosed no relevant financial relationships. Co-investigator Jaakko Kaprio, MD (University of Helsinki), reports having consulted for Pfizer on nicotine dependence from 2012 to 2014.

Stroke. Published online July 21, 2016. Abstract

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