Stroke Alert: A Review of Current Clinical Stroke Literature

Environmental and Lifestyle Impact on Stroke Risk

By Matthew E. Fink, MD, Professor and Chairman, Department of Neurology, Weill Cornell Medical College, and Neurologist-in-Chief, New York Presbyterian Hospital

Editor’s Note: This series of well-designed epidemiological studies emphasizes the importance of diet, sunlight exposure, stress, and vitamin deficiencies in the pathogenesis and risk of stroke.

Mediterranean Diet Can Reduce Risk for Stroke

Source: Estruch R, et al, for the PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; Feb. 25. DOI: 10.1056/NEJMoa1200303. [Epub ahead of print].

The predimed investigators from Barcelona, Spain, reported the results of their multicenter, randomized dietary treatment trial of the effects of three different diets on cardiovascular events — a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet that included advice to reduce dietary fat. The Mediterranean diet is characterized by a high intake of olive oil, fruit, nuts, vegetables, and cereals; a moderate intake of fish and poultry; a low intake of dairy products, red meat, processed meats, and sweets; and wine in moderation consumed with meals. A number of observational cohort studies suggested that this diet, over many years, might confer a reduced risk of cardiovascular disease, but this was the first large-scale, randomized study that directly compared diets. The primary endpoint was the rate of major cardiovascular diseases (myocardial infarction, stroke, death from cardiovascular causes), and the trial was stopped early (median follow-up of 4.8 years) when an interim analysis showed a significant difference in outcomes, based on which diet was instituted.

The enrolled subjects were free of cardiovascular disease, but had risk factors for disease — type 2 diabetes mellitus, or at least three of the following other risk factors: smoking, hypertension, elevated LDL, low HDL, obesity, or family history of premature coronary heart disease. A total of 7447 patients were enrolled (ages 55 to 80 years); 57% were women, and they were followed for a mean time of 4.8 years before the study was terminated. In a multivariable-adjusted analysis, the hazard ratios were 0.70 (95% confidence interval [CI], 0.54-0.92) for the Mediterranean diet with extra olive oil, and 0.72 (95% CI, 0.54-0.96) for the group assigned to the Mediterranean diet with nuts, vs the control group. For stroke alone, the hazard ratios for the two Mediterranean diets were 0.67 (olive oil) and 0.54 (nuts). Adherence to the Mediterranean diet results in a clinically and statistically significant reduction in cardiovascular events, especially stroke.

Low Levels of Light Exposure Associated with Higher Stroke Incidence

Source: Kent ST, et al. Short- and long-term sunlight radiation and stroke incidence. Ann Neurol 2013;73:32-37.

This investigation was a subject observational cohort of the REGARDS trial, which looked at a variety of risk exposures to African American and white patients living in the Southeastern Stroke Belt as well as the Southwest United States. Sunlight exposure was determined by using the North American Land Data Assimilation System dataset with calculation made for different regions over periods of 15-, 10-, 5-, 2-, and 1-year exposures. A cohort of 16,606 stroke and coronary artery disease-free black and white participants > 45 years were analyzed for these defined time periods, and compared for stroke risk using the lowest and highest quartiles of exposure to sunlight. After adjustment for other covariates, the previous year’s monthly average insolation exposure that was below the median gave a hazard ratio of 1.61 (95% CI, 1.15-2.26) and the previous year’s highest monthly average temperature exposure gave an HR of 1.92 (95% CI, 1.27-2.92).

The results of this study suggest that low light exposure increases stroke risk and that high temperature exposure increases stroke risk. The physiologic mechanisms related to these observations are unknown and require further investigation.

Psychosocial Stress Increases Risk of Stroke in Older Adults

Source: Henderson KM, et al. Psychosocial distress and stroke risk in older adults. Stroke 2013;44:367-372.

The investigators reported data from the Chicago Health and Aging Project, a longitudinal population-based study of community-dwelling black and non-Hispanic white adults, aged 65 years or older, living on the south side of Chicago. Psychosocial distress was measured from an analytically derived composite measure of depressive symptoms, perceived stress, neuroticism, and life dissatisfaction. A total of 6769 people were included and followed in this study. Cox proportional hazards ratio model was used to examine the association of distress with stroke incidence and mortality over a 6-year follow-up period.

The authors identified 151 stroke deaths and 452 incident strokes. After adjusting for age, race, and sex, the hazard ratio for each 1-standard deviation increase in distress was 1.47 (95% CI, 1.28-1.70) for stroke mortality and 1.18 (95% CI, 1.07-1.30) for incident stroke. Secondary analysis showed that distress was strongly related to hemorrhagic stroke (hazard ratio [HR],1.70) and not with ischemic stroke (HR, 1.02). In conclusion, the investigators stated that increasing levels of psychosocial distress are associated with an excess risk of stroke in older adults. The physiological mechanisms that underly this association (i.e., hypertension, cardiac arrhythmias, etc.) remain to be elucidated.

Vitamin D Deficiency May Increase Risk of Ischemic Stroke

Source: Brondum-Jacobsen P, et al. 25-hydroxyvitamin D and symptomatic ischemic stroke: An original study and meta-analysis. Ann Neurol 2013;73:38-47.

As part of the Copenhagen city heart study, investigators measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, and followed them for 21 years. During the follow-up period, 1256 developed ischemic strokes and 164 persons developed hemorrhagic strokes. A stepwise decrease in vitamin D levels was accompanied by a stepwide increase in the risk of ischemic stroke, and this varied by seasonal adjustments.

Using a Cox regression model comparing individuals with plasma vitamin D levels between the 1st and 4th percentiles to individuals with vitamin D concentrations between the 50th and 100th percentiles, the adjusted hazard ratio for ischemic stroke was 1.82 (95% CI, 1.41-2.34). Vitamin D levels were not associated with risk of hemorrhagic stroke. In a multivariate adjusted odds ratio of a meta-analysis of 10 other studies that examined vitamin D levels and stroke, comparing the lowest quartile with the highest quartile, the adjusted odds ratio for ischemic stroke was 1.54. This study confirms many others that vitamin D deficiency may increase the risk of ischemic stroke.