Reduced Lung Function a Risk Factor for SAH

Pam Harrison

August 23, 2012

August 23, 2012 — The contribution of reduced lung function to the development of subarachnoid hemorrhage (SAH) is comparable with the effects of hypertension and smoking — both known risk factors for SAH, new research shows.

Investigators from Lund University in Sweden found that reduced lung function, expressed as both forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), was significantly associated with an increased incidence of SAH.

At a mean follow-up of 25.7 years, patients in the lowest quartile of FEV1 had an unadjusted hazard ratio (HR) of 2.64 for SAH compared with patients in the highest FEV1 quartile.

Increased risk for SAH remained significant after established risk factors for SAH were taken into account, at an HR of 2.2 for the lowest vs the highest FEV1 quartiles. Furthermore, results were consistent when analysis was restricted to nonsmokers.

In contrast, no significant association was noted between SAH and FVC. Unlike FEV1 and FEV1/FVC, both of which are measures of pulmonary obstruction, FVC is more related to the volume of the lungs and often is increased in chronic obstructive lung disease (COPD) compared with reductions in both FEV1 and FEV1/FVC.

"Our hypothesis is that matrix degradation of vessel walls, which is the major reason for SAH, and degradation of lung tissue, which is a major reason for reduced FEV1, share common mechanisms," co-investigator Gunnar Engstrom, MD, PhD, also from Lund University in Sweden, told Medscape Medical News. "And results suggest that pulmonary obstruction and not lung volumes are of importance for the risk of SAH."

This study was published online August 7 in Stroke.

Incidence Higher in Women

Previous studies had shown that reduced lung function increases the risk for all-cause as well as ischemic stroke, but whether reduced lung function also increases the risk for SAH had not been previously studied.

Investigators sought to elucidate the relationship between lung function and the incidence of SAH in a large prospective cohort from an urban population.

Between 1974 and 1992, a large-scale screening program — The Malmo Preventive Project — was carried out to detect individuals at high risk for cardiovascular disease (CVD).

Spirometry was performed in complete birth cohorts during most but not all of the screening period. For this analysis, a total of 20,534 men and 7237 women, with a mean age of 44 years at baseline, were included.

At baseline, FEV1, FVC, and FEV1/FVC were 95.3%, 97%, and 98.2% of predicted, respectively, in men. In women, corresponding values were 95.8%, 97.4%, and 99.7%, respectively.

At follow-up, 98 men and 47 women had experienced an SAH, corresponding to an overall crude incidence of 20.3 per 100,000 person-years. The incidence of SAH was higher in women at 26.5 per 100,000 person-years than in men at 18.3 per 100,000 person-years.

Mean age at SAH was 59 years.

Table. Adjusted Hazard Ratios for SAH in Relation to Quartiles (Q) of FEV1 and FEV1/FVC

  Q4 (highest) Q3 Q2 Q1 (lowest) P Value for Trend
FEV1/HR 1 2.01 1.58 2.24 .014
FEV1/FVC 1 1.39 2.30 1.92 .003

FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HR, hazard ratio; SAH, subarachnoid hemorrhage.

"In the present cohort of middle-aged, healthy individuals, the risk of SAH was more than doubled in subjects with FEV1 in the lowest quartile as compared with those with FEV1 in the highest quartile, taking several possible confounders into account," the authors write.

When adjusted for smoking, "the HR for SAH in subjects with reduced lung function was even higher when the analysis was restricted to nonsmokers," they add.

Results were independent of systolic blood pressure — another important risk factor for SAH — as well as antihypertensive treatment at baseline. No significant interaction with hypertension was noted.

"Low FEV1 is a new risk factor for SAH, which may give new insights into the pathogenesis of SAH and help us to identify individuals at higher risk," Dr. Engstrom concluded. "[In the meantime], the first preventive measure patients can take to reduce SAH risk is to stop smoking and reduce exposure to environmental smoke, while the second most important way is to measure blood pressure regularly and treat hypertension with antihypertensive drugs."

Novel Finding

Ralph Sacco, MD, from the University of Miami, Leonard Miller School of Medicine, in Florida, told Medscape Medical News that identification of reduced lung volume as a risk factor for SAH is a "novel finding" that has not, to his knowledge, been reported before. "There have been other studies showing a relationship with reduced lung function with CVD and ischemic stroke, as the authors discuss," he noted.

However, identifying any new risk factor for SAH is not easy, as Dr. Sacco suggested, because SAH is much less frequent than other forms of stroke. Dr. Sacco also noted that Swedish investigators did control for other important risk factors for SAH, including smoking and hypertension.

Given this, the association between reduced lung function and SAH identified in the current study may indeed be a true one, although further studies are needed to confirm the association, and mechanism studies would be helpful, as Dr. Sacco indicated.

This study was supported by the Swedish Heart and Lung Foundation, the Swedish Stroke Foundation, Lundstrom's Foundation, the Swedish Research Council, and funds from both Lund University and Skane University Hospital. Dr. Engstrom has disclosed that he is employed as a senior epidemiologist by AstraZeneca R & D. Dr. Sacco has disclosed no relevant financial relationships.

Stroke. Published online August 7, 2012.

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