Increased Risk Of Ischemic Stroke Research Articles

Is Ischemic Stroke Risk Related to Folate Status or Other Nutrients Correlated With Folate Intake?

Folate status was inversely associated with plasma homocysteine concentration, a potential risk factor of cardiovascular disease. However, it is uncertain whether folate is causally associated with risk of ischemic stroke (IS). We aimed to examine the association between IS incidence and folate intake, biochemical folate status, and folate associated nutrients. Information on baseline characteristics and food frequency questionnaire was collected in 1990 to 1993 and included for analyses data from 1772 adults over 40 years, who were free of stroke and cancer at baseline from the CardioVascular Disease risk FACtor Two-township Study. Multivariate Cox proportional hazard model was used to relate baseline nutrient status with IS event. Over an average of 10.6 years of follow-up, 132 incident IS events were documented. Low folate intake (1st and 2nd quartiles) was significantly and independently associated with increased IS risk (HR=1.61; 95% CI: 1.04 to 2.48 and HR=1.82; 95% CI: 1.20 to 2.76) compared with those in the 3rd and 4th quartile combined, whereas no association was observed for plasma folate concentration. On the other hand, several nutrients correlated with dietary folate: vitamin B2, potassium, iron, vitamin A of plant origin, calcium were also associated with IS risk in an inverse linear manner with HR ranging from 1.5 to 1.9 for the first quartile. The protective association of dietary folate on IS risk may be in part through that of other correlated nutrients or other dietary components.

Clinical Epidemiology of Atrial Fibrillation and Related Cerebrovascular Events in the United States

Atrial fibrillation (AF) is an important, independent risk factor for stroke and is estimated to cause a 5-fold increase in ischemic stroke risk. The aim of this article is to describe the changing epidemiology of AF in the United States and to assess the implications for stroke prevention and treatment. AF prevalence is increasing in the general population. This is likely due to the aging of the population, the improvements in coronary care and the rising prevalence of AF risk factors such as diabetes. Risk factors such as rheumatic heart disease and hypertension have decreased in prevalence over the past few decades. However, novel risk factors such as obesity and possibly the metabolic syndrome have been identified and these have the potential to further increase AF prevalence. The utilization of warfarin has improved and this is reflected in falling ischemic stroke rates in the AF population. There is evidence for an increased incidence of anticoagulant associated intraparenchymal hemorrhages during the 1990s. Although the decline in stroke rates in AF is laudable, the rising prevalence of AF, the changing profile of risk factors, and the recent plateauing of warfarin use indicate that stroke in AF patients will continue to be a significant public health problem.

Variation in 24 hemostatic genes and associations with non-fatal myocardial infarction and ischemic stroke.

Arterial thrombosis involves platelet aggregation and clot formation, yet little is known about the contribution of genetic variation in fibrin-based hemostatic factors to arterial clotting risk. We hypothesized that common variation in 24 coagulation-fibrinolysis genes would contribute to risk of incident myocardial infarction (MI) or ischemic stroke (IS). We conducted a population-based, case-control study. Subjects were hypertensive adults and postmenopausal women 30-79 years of age, who sustained a first MI (n = 856) or IS (n = 368) between 1995 and 2002, and controls matched on age, hypertension status, and calendar year (n = 2,689). We investigated the risk of MI and IS associated with (i) global variation within each gene as measured by common haplotypes and (ii) individual haplotypes and single nucleotide polymorphisms (SNPs). Significance was assessed using a 0.2 threshold of the false discovery rate q-value, which accounts for multiple testing. After accounting for multiple testing, global genetic variation in factor (F) VIII was associated with IS risk. Two haplotypes in FVIII and one in FXIIIa1 were significantly associated with increased IS risk (all q-values < 0.2). A plasminogen gene SNP was associated with MI risk. All are new discoveries not previously reported. Another 24 tests had P-values < 0.05 and q-values > 0.2 in MI and IS analyses, 23 of which are new and hypothesis generating. Apart from the association of FVIII variation with IS, we found little evidence that common variation in the 24 candidate fibrin-based hemostasis genes strongly influences arterial thrombotic risk, but our results cannot rule out small effects.

Can Biomarkers Identify Women at Increased Stroke Risk? The Women's Health Initiative Hormone Trials

Objective:The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy (HT).Design:The hormone trials were randomized, double-blind, and placebo controlled.Setting:The Women's Health Initiative trials were conducted at 40 clinical centers in the United States.Participants:The trials enrolled 27,347 postmenopausal women, aged 50–79 y.Interventions:We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo.Outcome Measures:Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial.Results:No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin (odds ratio 1.28) but were when assigned to placebo (odds ratio 3.47; p for difference = 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant (p = 0.03).Conclusions:Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance.

Long-term Risk of Ischemic Stroke Associated with Rofecoxib

The association between rofecoxib use and ischemic stroke has not been shown in clinical trials. These trials were limited by short-term follow-up and non-placebo controls. Extended follow-up data from the APPROVe trial has shed some light on the incidence of ischemic stroke after rofecoxib use. Review of published and unpublished data from APPROVe. We searched the Food and Drug Administration and Merck websites to obtain unpublished data. Statistical analyses were performed by the APPROVe investigators and are reported as relative risks (RR) with their 95% confidence intervals (CI). APPROVe evaluated the effect of rofecoxib 25 mg/d versus matching placebo on recurrent colon polyps in 2,586 patients with a history of colorectal adenomas. Although the published data from APPROVe showed a nonsignificant relative risk of ischemic stroke (RR 1.99, 95% CI 0.74 to 5.39, p = 0.174), extended follow-up data from Merck's website recently revealed a significant three-fold increase in ischemic stroke in patients randomized to rofecoxib (RR 2.91, 95% CI 1.15 to 7.39, p = 0.024). Notably, seven out of eighteen ischemic strokes occurred after rofecoxib use had been discontinued. Based on extended follow-up data, APPROVe is the first trial to report an increase in ischemic stroke risk with rofecoxib compared to placebo. The finding of ischemic strokes after rofecoxib use had been discontinued should be further studied to determine whether patients previously exposed to rofecoxib remain at an increased risk.

Dose-Related Association of MTHFR 677T Allele With Risk of Ischemic Stroke

Data are conflicting concerning ischemic stroke risk associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyperhomocystinemia in vivo. We performed a systematic review and meta-analysis of published relevant literature. We included cohort, case-control, or cross-sectional studies reporting the frequencies of heterozygous (CT) and homozygous (TT) genotypes in (a) all stroke/TIA (overall group) and (b) imaging-proven ischemic stroke (best-phenotyped group). Among 14 870 subjects, the pooled estimated risk of stroke/TIA associated with the 677T allele increased in a dose-dependent manner (T allele pooled OR 1.17, 95%CI 1.09 to 1.26, TT genotype pooled OR 1.37, 95%CI 1.15 to 1.64). An almost-identical relationship was observed when the analysis was restricted to imaging-proven ischemic stroke (T allele pooled OR 1.18, 95%CI 1.09 to 1.29, TT genotype pooled OR 1.48, 95%CI 1.22 to 1.8). A graded increase in ischemic stroke risk with increasing MTHFR 677T allele dose was observed, suggesting an influence of this polymorphism as a genetic stroke risk factor and supporting other evidence indicating a causal relationship between elevated homocysteine and stroke.

Family history and socioeconomic factors as predictors of myocardial infarction, unstable angina and stroke in an Italian population. PROGETTO 3A Investigators.

A comprehensive case-control study was conducted in an Italian region in order to compare the influence of family history of cardiovascular events, socioeconomic factors, social networks, and their joint associations with major risk factors, on the risk, of myocardial infarction (MI), unstable angina (UA) and ischemic stroke (IS). A total of 513 patients with MI, 178 with UA, 237 with IS, and 928 hospitalised controls were recruited. The odds ratio (OR) of MI for two or more relatives with a positive history of MI was 3.6 (95% CI: 1.8-7.3). Family history of MI was predictive for UA (OR = 5.8; 95% CI: 1.2-28.7), but not for IS. A family history of stroke was more associated with the risk of MI than of IS. After adjustment for known risk factors, the OR of MI for more educated people was 2.1 (1.3-3.6) compared with less-educated people. Large family size seemed to be protective for MI. The effect of major risk factors on MI ranged from additive (diabetes) to multiplicative jointly with high education and family history of MI. A family history of stroke increased IS risk threefold jointly with smoking and hyperlipidemia, and eightfold with diabetes. Besides a family history of MI and IS, in this community a higher educational status seems to better identify groups at increased risk of MI. The joint associations have important preventive implications since by identifying high-risk individuals (for MI and IS) a more careful assessment and control of risk factors amenable to intervention may be performed.