Stroke Epidemiology

Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and …

by Michael V Holmes

Co-authored with Newcombe P, Hubacek JA, Sofat R, Ricketts SL, Cooper J, Breteler MM, Bautista LE, Sharma P, Whittaker JC, Smeeth L, Fowkes FG, Algra A, Shmeleva V, Szolnoki Z, Roest M, Linnebank M, Zacho J, Nalls MA, Singleton AB, Ferrucci L, Hardy J, Worrall BB, Rich SS, Matarin M, Norman PE, Flicker L, Almeida OP, van Bockxmeer FM, Shimokata H, Khaw KT, Wareham NJ, Bobak M, Sterne JA, Smith GD, Talmud PJ, van Duijn C, Humphries SE, Price JF, Ebrahim S, Lawlor DA, Hankey GJ, Meschia JF, Sandhu MS, Hingorani AD, Casas JP.

BACKGROUND:
The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and... more BACKGROUND:
The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials.
METHODS:
We established a collaboration of genetic studies consisting of 237 datasets including 59,995 individuals with data for homocysteine and 20,885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45,549 individuals, 2314 stroke events, 269 transient ischaemic attacks).
FINDINGS:
The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, -0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region.
INTERPRETATION:
In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C→T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption.

Development, Expansion and Use of a Stroke Clinical Trials Resource for Novel Exploratory Analyses (in press) International Journal of Stroke.

by Marian Brady

Ali M, Bath P, Brady M, Davis S, Diener H-C, Donnan G; Fisher M, Hacke W, Hanley DF, Luby M, Tsivgoulis G, Wahlgren N, Warach S, Lees KR, on behalf of the VISTA Steering Committees.

Dispositional Optimism Protects Older Adults From Stroke: The Health and Retirement Study

by Eric S. Kim

Published in: Stroke

Background and Purpose—Although higher optimism has been linked to an array of positive health outcomes, the... more Background and Purpose—Although higher optimism has been linked to an array of positive health outcomes, the association between optimism and incidence of stroke remains unclear, especially among older adults. We examined whether higher optimism was associated with a lower incidence of stroke.

Method—Prospective data from the Health and Retirement Study—a nationally representative panel study of American adults aged >50 years—were used. Analyses were conducted for a 2-year follow-up on the subset of 6044 adults (2542 men, 3502 women) who were stroke-free at baseline. Analyses adjusted for chronic illnesses, self-rated health, and relevant sociodemographic, behavioral, biological, and psychological factors.

Results—Higher optimism was associated with a lower risk of stroke. On an optimism measure ranging from 3 to 18, each unit increase in optimism was associated with an age-adjusted OR of 0.90 for stroke (95% CI, 0.84 to 0.97; P<0.01). The effect of optimism remained significant even after fully adjusting for a comprehensive set of sociodemographic, behavioral, biological, and psychological stroke risk factors.

Conclusions—Optimism may play an important role in protecting against stroke among older adults.

Clinical Presentation and Epidemiology of Stroke :A Study of 100 Cases

by Md. Shahriar Mahbub

Co-authored with Md Abu Naser Siddique, Zannatun Nur, Md Billal Alam, Md Titu Miah

Journal of Medicine 2009; 10 : 86-89

doi: 10.3329/jom.v10i2.2820

The stroke patients comprise a large number of hospital admissions and stroke is one of leading cause of significant... more The stroke patients comprise a large number of hospital admissions and stroke is one of leading cause of significant mortality and morbidity. This prospective observational study was carried out among 100 hospitalized stroke patients admitted into different medicine units of Chittagong Medical College Hospital (CMCH), with a view to study clinical presentation and epidemiology of stroke. Data, collected in prescribed protocol, were analyzed in simple statistical percentage and cases were selected irrespective of age and sex. Stroke was found most commonly in 51-60 age group (45%in hemorrhagic and 51.75% in ischemic stroke).Most of the patients were male with male, female ratio 3:1 in hemorrhagic stroke and 1.35:1 in ischemic stroke. Most of the patients were from rural area (60% in hemorrhagic stroke and 57.5 in ischemic stroke). Ischemic stroke was found in 80% cases and hemorrhagic stroke was found in 20% cases. The commonest presentation in both ischemic and hemorrhagic stroke was hemiplegia or hemiparesis. Rightsided hemiparesis was the predominant finding in both types. Headache (60%) and vomiting (75%) were found to be more common accompaniment of hemorrhagic stroke. In case of ischemic stroke the association with these clinical features was less marked where headache was present in 46.25% and vomiting in 40% cases. 50% of patients of hemorrhagic stroke presented with Glasgow Coma Scale (GCS) level 9-12(grade2) and 5% with GCS level 4 - 8(Grade 3). Whereas, 52.5% of patients of ischemic stroke presents with GCS 9-12 and also 46.25% with GCS13-14 (grade 1). Hypertension was the commonest risk factor associated with both types of stroke. In hemorrhagic stroke it was 80% and in ischemic stroke it was found in 56.25% eases. Smoking was associated with 50% of hemorrhagic and 55% of ischemic stroke. Diabetes mellitus was associated with 26.25% of ischemic stroke