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Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population.

ABSTRACT: We previously reported increased incidence of ischemic stroke among both blacks and whites with diabetes mellitus, especially in those aged <55 years. With rising prevalence of diabetes mellitus in the past decade, we revisit the impact of diabetes mellitus on stroke incidence in the same population (?1.3 million) 5 and 10 years later.This is a population-based study. First ischemic strokes among black and white residents of the 5-county Greater Cincinnati/Northern Kentucky region, aged ? 20 years, for periods 7/1993 to 6/1994, 1999, and 2005, were included in this analysis. Incidence rates were adjusted for sex, race, and age, as appropriate, to the 2000 US population.History of diabetes mellitus among first ischemic strokes was reported for 493/1709 (28%) in 1993/1994, 522/1778 (29%) in 1999, and 544/1680 (33%) in 2005. Risk ratios (95% confidence interval) for rates of stroke in those with versus without diabetes mellitus for blacks reduced significantly from 5.6 in 1993/1994 to 3.2 in 2005; for whites the risk ratio remained stable at 3.8 in 1993/1994 and 2005. However, risk ratios varied with age, with an overall 5- to 14-fold increased risk observed in those aged 20 to 65 years.Those with diabetes mellitus remain at greatly increased risk for stroke at all ages, especially <65 years, regardless of race. The rates and risk ratios for 1999 and 2005, although similar to those previously reported for the mid-1990s, take on increased significance, given the epidemic of diabetes mellitus and metabolic syndrome throughout the US and the world.

SUBMITTER: Khoury JC

PROVIDER: S-EPMC3746032 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population.

Khoury Jane C JC Kleindorfer Dawn D Alwell Kathleen K Moomaw Charles J CJ Woo Daniel D Adeoye Opeolu O Flaherty Matthew L ML Khatri Pooja P Ferioli Simona S Broderick Joseph P JP Kissela Brett M BM

Stroke 20130425 6

<h4>Background and purpose</h4>We previously reported increased incidence of ischemic stroke among both blacks and whites with diabetes mellitus, especially in those aged <55 years. With rising prevalence of diabetes mellitus in the past decade, we revisit the impact of diabetes mellitus on stroke incidence in the same population (≈1.3 million) 5 and 10 years later.<h4>Methods</h4>This is a population-based study. First ischemic strokes among black and white residents of the 5-county Greater Cin ...[more]

PMID: 23619130

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Project description:BACKGROUND:Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by current cigarette smoking status. METHODS:A population-based case-control study of stroke among women aged 15-49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-comparable control subjects (43.1% African-American). Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status. RESULTS:Of the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0-5.0, p = 0.049; risk factor adjusted: OR = 2.5, 95% CI = 1.0-6.5, p = 0.05). When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI = 0.11-.082, p = 0.02), but not among smokers (OR = 1.63, 95% CI = 0.48-5.58, p = 0.43); genotype by smoking interaction (p = 0.036). Second, the C allele (frequency = 39%) of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09-3.86, p = 0.03), but not among non-smokers (OR = 0.93, 95% CI = 0.62-1.39, p = 0.72); genotype by smoking interaction (p = 0.039). CONCLUSION:This study demonstrates that inflammatory gene SNPs are associated with early-onset ischemic stroke among African-American women (IL6) and that cigarette smoking may modulate stroke risk through a gene-environment interaction (IL6 and CD14). Our finding replicates a prior study showing an interaction with smoking and the C allele of CD14 SNP rs2569190.

Project description:In a recent meta-analysis migraine was associated with a two-fold increase in stroke risk. While the mechanism driving this association is unknown, one intriguing hypothesis is that migraineurs are genetically predisposed to developing ischemic stroke. Mutations in the ATP1A2 gene are implicated in familial hemiplegic migraine type II and increase the severity of ischemic brain injury in animal models. To further explore these observations, we assessed the association between ATP1A2 polymorphisms, migraine, and the risk of ischemic stroke in participants of the Genetics of Early-Onset Stroke Study, a population-based case-control study of ischemic stroke among men and women aged 15-49. Using responses to a headache symptoms questionnaire, subjects were classified as having no migraine, or migraine with or without visual aura. Evaluating a total of 134 ATP1A2 polymorphisms genotyped using a combination of Illumina platforms (Cardiovascular Gene-centric 50 K SNP Array and HumanOmni1-Quad_v1-0_B Bead Chip), only one polymorphism (rs2070704) demonstrated a nominally significant association with stroke in an age-, gender-, ethnicity-adjusted model (OR?=?0.83, 95% CI?=?0.71-0.98, p?=?0.025) and in a vascular risk factor model adjusting for age, gender, ethnicity, hypertension, diabetes, smoking, and myocardial infarction (OR?=?0.74, 95% CI?=?0.63-0.89, p?=?0.001). Ethnicity-stratified analyses demonstrated a significant association for rs2070704 among African-Americans (OR?=?0.68, 95% CI?=?0.53-0.90, p?=?0.005) but not Caucasians (OR?=?0.82, 95% CI?=?0.64-1.04, p?=?0.107). These associations were unchanged when migraine subtypes were included as co-variates. We did not observe an association between ATP1A2 polymorphisms and migraine. While our results do not demonstrate a strong relationship between ATP1A2 polymorphisms and migraine associated stroke risk, the results are hypothesis generating and indicate that an association between ATP1A2 polymorphisms and stroke risk may exist. Additional studies are required.

Project description:Background and Purpose- Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods- Using data from the Get With The Guidelines-Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3- to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results- Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5-15] versus 7 [4-13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P=0.31) and 6.2% versus 5.5% ( P=0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51-1.21]; P=0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52-1.14]; P=0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0-2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59-0.99]; P=0.04). Conclusions- Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3- to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.

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Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population.

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Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population.

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