Stroke Alert: A Review of Current Clinical Stroke Literature

By Matthew E. Fink, MD, Interim Chair and Neurologist-in-Chief, Director, Division of Stroke & Critical Care Neurology, Weill Cornell Medical College and New York Presbyterian Hospital

Obesity a Major Risk Factor for Stroke that Should Be Modified

Yatsuya H, et. al. Race and sex-specific association of obesity measures with ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2010; DOI: 10.1161/STROKE.109.566299

In this prospective, population-based study of 13,549 middle-age black and white men and women in four U.S. communities, who, at the time of enrollment were free of cancer and cardiovascular disease, the investigators showed that abdominal obesity raised the risk of stroke in all groups, men and women, white and black.

The thinnest white women suffered about 1.2 strokes per 1,000 person-years, while their black counterparts suffered 4.3 strokes per 1,000 person-years. Obese black men had the highest incidence of stroke — 8.0 per 1,000 person-years. In all comparative groups, obese black men and women had between two and three times the stroke risk of their white counterparts. Correction for hypertension and diabetes attenuated the effect of obesity, but both of these conditions are strongly associated with obesity. Although there is no proof from any randomized clinical trials, we believe that aggressive weight reduction should be part of any stroke risk reduction program. But, it will take decades to prove this hypothesis.

Aspirin Alone or Aspirin Plus Extended-release Dipyridamole Is Equally Effective as Early Treatment for Transient Ischaemic Attack or Stroke

Dengler R, et al. Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischemic stroke within 24 h of symptom onset (EARLY trial): a randomized, open-label, blinded-endpoint trial. Lancet Neurol 2010;9:159-166.

Treatment guidelines recommend antiplatelet therapy for patients with non-cardioembolic stroke or TIA (aspirin 50–325 mg, aspirin plus extended-release dipryridamole, or clopidogrel). For long-term secondary prevention of stroke, aspirin plus extended-release dipyridamole (ASA-DPM) has been shown to be more effective than aspirin monotherapy, and clopidogrel is more effective in reducing combined vascular events and death. Based on the PRoFESS trial, there is no difference between clopidogrel and ASA-DPM in stroke recurrence.

However, the best antiplatelet treatment in the acute setting of stroke and TIA is unknown because the secondary prevention trials enrolled patients anywhere from one month to six months after symptom onset. The EARLY trial was designed to answer this question by enrolling 543 patients within 24 hours of symptom onset. Half received 100 mg of aspirin daily for the first seven days; the other half received ASA-DPM for the first seven days, and then all of the patients were treated with ASA-DPM until follow-up at 90 days. The primary end point was the modified Rankin scale score, and there was no significant difference between the groups at 90 days. A composite secondary outcome that looked at adverse events (non-fatal stroke, TIA, non-fatal myocardial infarction, major bleeding, and mortality) also showed no significant differences between the groups at 90 days. There was a higher dropout rate in the early ASA-DPM group due to headache.

Reducing Salt Intake Will Reduce the Risk of Stroke and Death

Bibbins-Domingo K, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med 2010; Jan 20 [Epub ahead of print].

The u.s. diet is high in salt, mostly from processed foods. Men consume more than 10 gm of salt per day and women more than 7 gm per day, far in excess of the recommendations of the Department of Health and Human Services. Hypertension remains a major public health challenge, with less than 50% of those affected getting optimal treatment, and the age-adjusted incidence of hypertension is rising.

In this setting, the investigators created a model for determining the health benefits of a population-wide reduction in dietary salt by 3 gm per day — a realistic and achievable level. A successful effort to reduce dietary salt could reduce new cases of stroke by 32,000 to 66,000 and reduce annual deaths from any cause by 44,000 to 92,000. The entire population would benefit, with blacks receiving a greater benefit than whites, and women having a greater reduction in stroke compared to men. Health care costs could be reduced by $10 billion to $24 billion, and dietary salt reduction would be more cost-effective than using blood pressure medications to lower blood pressure for everyone who has hypertension.

Proteinuria Associated with Cerebral Micro-bleeds, and May Predict Future Risk for Intracerebral Hemorrhage

Ovbiagele B, et al. Strong independent correlation of proteinuria with cerebral microbleeds in patients with stroke and transient ischemic attack. Arch Neurol 2010;67:45-50.

From an observation never before analyzed, the investigators correlated the degree of proteinuria with the presence and number of cerebral microbleeds (CMB), as measured on gradient-echo T2-weighted MRI, in an unselected group of patients with ischemic stroke and TIA. Of 236 patients (mean age, 70 years; 53% female), 31% had CMB and 38% had proteinuria. In a multivariable analysis with presence of CMB as the outcome, the following associations were found — higher urinary protein (OR = 2.33), being female (OR = 2.2.9), atrial fibrillation (OR = 2.49), elevated homocysteine (OR = 1.1.9), small-vessel disease subtype (OR = 2.95). All were associated with a higher number of CMB.

The authors speculate that the association of CMB and proteinuria may indicate a widespread endothelial dysfunction that results in blood vessel fragility and leakage of protein, as well as small bleeds from small cerebral arteries. We have no way to know how many of these patients might have cerebral amyloid angiopathy and whether proteinuria is associated with that disorder. Regarding treatment, the authors stress the importance of good blood pressure control to help the brain as well as the kidneys.