Additive interaction between potentially modifiable risk factors and ethnicity among individuals in the Han, Tujia and Miao populations with first-ever ischaemic stroke

China has had explosive growth in ischemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to explore the possible combination effect between gut microbiota and traditional potentially modifiable risk factors for IS among two ethnic minorities (Tujia and Miao) and the Han population. Herein, we first used the 16 S rRNA sequencing to compare the gut microbial compositions of 82 patients with first-ever IS vs. 82 normal controls (NCs) among Han, Tujia, and Miao people between 1 May 2018 and 30 April 2019, from Xiangxi Tujia and Miao Autonomous Prefecture in China. An additive model was used to study the interaction between traditional risk factors and gut microbiota with R software. Linear discriminant analysis (LDA) and LDA effect size (LEfSe) results showed that the identified key gut microbiota's taxonomic composition varied in different ethnicity between the IS patients and NCs. Furthermore, families Lactobacillaceae, Enterococcaceae, Streptococcaceae, and Enterobacteriaceae were found to be positively correlated with high-risk factors and negatively correlated with preventive factors in the IS patients, but families Ruminococcaceae and Lachnospiraceae were just the opposite in the NCs. There were additive interactions between traditional risk factors (systolic blood pressure, diastolic blood pressure, and high-sensitive C-reactive protein) and family Enterococcaceae for first-ever IS with the attributable proportion due to the interaction was 0.74, 0.71, and 0.85, respectively; and the synergy index was 4.45, 3.78, and 7.01, respectively. This preliminary but promising study showed that the gut microbiota disturbances may potentially interact to IS with different ethnic host's traditional risk factors.

To find a rapid single nucleotide polymorphism (SNP) loci typing method in the mitochondrial DNA (mtDNA) coding regions, we genotyped 16 SNP loci in the mitochondrial DNA coding region in Han, Miao and Tujia populations by the multiplex-amplified product-length polymorphism (mAPLP) technique. This method generates allele-specific fragments that are different in length through PCR amplification using allele-specific forward (or reverse) primers different in size and a common reverse (or forward) primer. Results showed that both of the allelic frequency of 3970T in Han and Tujia populations were 17%, which were significantly different from that of in the Miao population (P0.01). The allelic frequency of 8020A in Han population was 6% , which was different from that of in the Miao and Tujia populations (P0.05) . In all of 300 samples, a total of 45 different haplotypes were identified, 12 of which were found in all the three populations, 10 were shared by two populations and 23 haplotypes existed only in one of the populations. Among these 23 haplotypes, 8, 6 and 12 haplotypes were exclusively observed in the Han, Miao and Tujia populations, respectively.

Standard 12-lead electrocardiography is a routine and mandatory cardiovascular examination in the evaluation of stroke patients. This study investigates the relationship of electrocardiography findings and first-ever ischemic stroke. This hospital-based case-control study consisted of 238 consecutively hospitalized cases of first-ever ischemic stroke and 238 healthy age- and sex-matched control subjects. Multivariate logistic regression analyses were performed to evaluate the risk factors and electrocardiography findings. Atrial fibrillation [odds ratio (OR) = 6.8, 95% confidence interval (CI) =1.90-24.45], myocardial ischemic change (OR = 5.0, 95% CI = 2.22-11.06), left ventricular hypertrophy (OR = 3.9, 95% CI = 2.02-7.39) and sinus bradycardia (OR = 0.37, 95% CI = 0.18-0.79) were significantly related with first-ever ischemic stroke. Electrocardiography findings of atrial fibrillation, myocardial ischemic change and left ventricular hypertrophy as risk factors for ischemic stroke were similar to those from other studies. Additional studies are needed to assess the role of sinus bradycardia for ischemic stroke, which was less common in patients with stroke than in controls.

Elevated plasma homocyst(e)ine may be a causal and modifiable risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that homocyst(e)ine may only be associated with certain pathophysiological subtypes of ischemic stroke. We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by etiologic subtype in a blinded fashion. The prevalence of conventional vascular risk factors, fasting plasma homocyst(e)ine levels, vitamin levels, and nucleotide 677 methylene tetrahydrofolate reductase (MTHFR) genotypes were determined in cases and controls. Increasing homocyst(e)ine was a strong and independent risk factor for ischemic stroke (adjusted OR 2.7, 95% CI 1.4 to 5.1 for a 5-micromol/L increase in fasting plasma homocyst(e)ine from 10 to 15 micromol/L). Compared with the lowest quartile, the highest quartile of homocyst(e)ine was associated with an adjusted OR of ischemic stroke of 2.2 (95% CI 1.1 to 4.2). Mean plasma homocyst(e)ine was significantly higher in cases of ischemic stroke due to large-artery disease (14.1 micromol/L, 95% CI 12.5 to 15.9, P<0.001) and small-artery disease (12.7 micromol/L, 95% CI 11. 4 to 14.1, P=0.004) compared with control subjects (10.5 micromol/L; 95% CI 10.0 to 11.0) but not in cardioembolic or other etiologic subtypes of ischemic stroke. Compared with the lowest quartile of homocyst(e)ine, the upper 3 quartiles were associated with an adjusted OR of ischemic stroke due to large-artery disease of 3.0 (95% CI 0.8 to 10.8) for the second quartile, 5.6 (95% CI 1.6 to 20) for the third quartile, and 8.7 (95% CI 2.4 to 32) for the fourth quartile (P for trend=0.0005). However, despite a clear association between the TT MTHFR genotype and elevated fasting plasma homocyst(e)ine, there was no association between MTHFR genotype and ischemic stroke or subtype of ischemic stroke. There is a strong, graded association between increasing plasma homocyst(e)ine and ischemic stroke caused by large-artery atherosclerosis and, to a much lesser extent, small-artery disease, but not cardioembolic or other etiologic subtypes of ischemic stroke. Our results are consistent with the hypothesis that the deleterious effect of high homocyst(e)ine is mediated primarily via a proatherogenic effect.

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Risk factors for ischemic stroke is suggested to differ by etiologic subtypes. The purpose of this study was to examine the associations between modifiable and non-modifiable risk factors and atherothrombotic stroke (i.e., excluding cardioembolic stroke), and to examine if the potential benefit of modifiable lifestyle factors differs among subjects with and without predisposing comorbidities. After a median follow-up of 21.2 years, 2339 individuals were diagnosed with atherothrombotic stroke out of 26,547 study participants from the Malmö Diet and Cancer study. Using multivariable Cox regression, we examined non-modifiable (demographics and family history of stroke), semi-modifiable comorbidities (hypertension, dyslipidemia, diabetes mellitus and atherosclerotic disease), and modifiable (smoking, body mass index, diet quality, physical activity, and alcohol intake) risk factors in relation to atherothrombotic stroke. Higher age, male gender, family history of stroke, and low educational level increased the risk of atherothrombotic stroke as did predisposing comorbidities. Non-smoking (hazard ratio (HR) = 0.62, 95% confidence interval (CI) 0.56–0.68), high diet quality (HR = 0.83, 95% CI 0.72–0.97) and high leisure-time physical activity (HR = 0.89, 95% CI 0.80–0.98) decreased the risk of atherothrombotic ischemic stroke independent of established risk factors, with non-significant associations with body mass index and alcohol intake. The effect of the lifestyle factors was independent of predisposing comorbidities at baseline. The adverse effects of several cardiovascular risk factors were confirmed in this study of atherothrombotic stroke. Smoking cessation, improving diet quality and increasing physical activity level is likely to lower risk of atherothrombotic stroke in the general population as well as in patient groups at high risk.

PurposeThis study aimed to assess the risk factors for acute first-ever ischaemic stroke (IS) in the elderly population aged ≥60 years in the eastern part of Liaoning Province, China.Patients and MethodsThis retrospective case-control study was derived from the Benxi Clinical Biobank and the Thrombotic Chronic Non-Communicable Disease Cohort Study in Natural Populations in Eastern Liaoning (ChiCTR2300074593). We collected cases of acute IS in the elderly population and selected the corresponding controls in a 1:1 ratio for inclusion in the study. Data collection included sociodemographics, clinical characteristics, and laboratory characteristics. We used IBM SPSS Statistics V26.0 for Windows for descriptive statistical analysis and conditional logistic regression analysis to determine risk factors for IS.ResultsThis study included 326 cases (163 pairs) of study subjects. The median age of the cases and controls was 65 years (62–70). Both groups were predominantly 60–69 years old in the age subgroups, 69.3% in the case group and 74.2% in the control group, with a p-value of 0.011; females in both groups accounted for 49.1% in the case group and 49.1% in the control group. Variables with P < 0.05 in the univariate analysis included current smoking, current alcohol consumption, fasting blood glucose, and hypertension. Variables statistically significant in the univariate analysis entered into the multivariate multifactorial analysis. The results showed that hypertension (OR, 1.977; 95% CI, 1.322–2.956) and current alcohol consumption (OR, 1.549; 95% CI, 1.086–2.210) were independent risk factors for acute first-ever IS in the elderly population aged ≥60 years.ConclusionHypertension and current alcohol consumption are major risk factors for IS in an elderly population in eastern Liaoning Province.

Predictors of ischemic cardiovascular disease in middle-age Chinese with optimal low-density lipoprotein cholesterol

Background:Obstructive sleep apnoea (OSA) syndrome is an established and modifiable but under recognized risk factor for common disorders like stroke and hypertension.Objective:To assess awareness level of health care practitioners and medical students about OSA as a risk factor for stroke and hypertension.Methods:Questionnaire based survey with multiple response type and fill in the blanks type questions. The data was compiled and analyzed using SPSS version 19.Results:180 participants completed the survey questionnaire. Only 24 (13.3%) identified OSA as a reversible risk factor for ischemic stroke. 11 (6%) participants only could answer OSA as an identified risk factor for hypertension as per Seventh Joint National Committee report.Conclusion:This study reveals dismal level of awareness, among health professionals and medical students, about OSA being an established and modifiable risk factor for hypertension and ischemic stroke.

Impact of the 1425G/A Polymorphism of PRKCH on the Recurrence of Ischemic Stroke: Fukuoka Stroke Registry

Risk factors of young ischemic stroke in Qatar

Two common polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012 (approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group (P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke (OR = 1.844, 95% CI: 1.286-2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke (OR = 1.366, 95% CI: 1.077-1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype (OR = 2.953, 95% CI: 2.082-4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction (OR = 3.404, 95% CI: 1.631-7.102, P < 0.001) and additive interaction (RERI = 41.705, 95% CI: 14.586-68.824, AP = 0.860; 95% CI: 0.779-0.940; S = 8.170, 95% CI: 3.772-17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele (OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele (OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.

BACKGROUND:Cardiovascular diseases, hypertension, diabetes mellitus, dyslipidemia, and atrial fibrillation are the most common modifiable risk factors for recurrent ischemic stroke. In this study, we aimed to find the risk factors associated with more than two recurrent ischemic strokes after the first-ever stroke.METHODS:We collected the ischemic stroke patients in our stroke registry data bank, and the eligible patients were followed for recurrent ischemic stroke after 2008. Our study consisted of 927 patients who were followed up for 9 years after the first-ever stroke.RESULTS:We found that 185 (20%) patients had a recurrent ischemic stroke, and another 32 (3.5%) patients had more than one recurrence after the first-ever ischemic stroke. The mean time for the first stroke recurrence was 1 year, and the mean time for the multiple stroke recurrences was 3 years. Significant risk factors for multiple recurrences were congestive heart disease (P < 0.015) and diabetes mellitus (P < 0.006).CONCLUSIONS:We concluded that even with the appropriate treatments, patients with congestive heart disease and diabetes mellitus have a higher rate of multiple recurrences for ischemic stroke after the first-ever ischemic stroke, indicating that more attention should be paid to this issue.

Background and Purpose: The association between anticardiolipin antibody (aCL) and ischemic stroke is controversial, and there are few case-control studies of Asian populations. The aim of this study, therefore, was to determine whether aCL is an independent risk factor for ischemic stroke in Taiwanese patients over the age of 40 years. Methods: Both the IgG and IgM isotypes of aCL were measured in 273 patients (>40 years of age) hospitalized for first-ever ischemic stroke and in 181 non-stroke controls. Results were defined as: negative (<10 IgG phospholipid units [GPL] or <7.5 IgM phospholipid units [MPL]); low positive (10–20 GPL or 7.5–15 MPL); or, high positive (>20 GPL or >15 MPL). Odds ratios (OR) were estimated by logistic regression with adjustment for potential confounders. Results: A high positive IgG aCL was present in 4.4% of the stroke patients and 1.2% of the controls. Age- and sex-adjusted analysis showed a borderline association between a high positive level for aCL IgG titer and stroke, with an OR of 4.01 (95% CI 0.87–18.37; p = 0.0739). Final analysis, with adjustments for age, sex, hypertension, diabetes, tobacco smoking, atrial fibrillation, left ventricular hypertrophy and hyperlipidemia, revealed an OR of 5.25 (95% CI 1.06–25.89; p = 0.0419). Conclusions: The results of this study suggest that elevated titer of aCL IgG (>20 GPL) is associated with first-ever ischemic stroke in Taiwanese patients aged over 40 years. High positive aCL titer is related to ischemic stroke after adjustment for conventional cerebrovascular risk factors, indicating that it is probably an independent risk factor for ischemic stroke.

Stroke remains a leading cause of disability and death for people of all races and ethnicities. Nearly 800 000 Americans experience a stroke each year—1 every 40 seconds—and ≈135 000 die.1 Approximately 600 000 of these are first or new strokes, and those who survive are at increased risk of a future stroke.1 In 2010, strokes cost the United States an estimated $53.9 billion, including both healthcare costs and productivity losses.2 There are significant racial and ethnic disparities in stroke rates, with blacks having nearly twice the risk of whites of having a first stroke,1 and blacks and Hispanics are more likely to die after a stroke than are whites.1 There are also geographic disparities, with higher stroke incidence in the southeastern United States.3 And although stroke risk increases with age, strokes can occur at any age; about 25% of strokes occur in people who are <65 years of age.3a Stroke is the leading cause of serious long-term adult disability in the United States. As many as 30% of people who experience a stroke become permanently disabled, losing their speech, sight, mobility, and the ability to perform the simplest life tasks.4 For some, the final years of life can be transformed in an instant from what had been envisioned as an enjoyable time spent with family and friends to one of frustration, isolation, and despair. As the US population ages, the burden of cardiovascular diseases, including stroke, is expected to increase dramatically in coming decades. Assuming no changes in current trends, by 2030, the prevalence of stroke is projected to increase by 25%, and the economic costs of stroke will nearly triple.2 Because improvements in medical care are reducing stroke mortality even further, the prevalence of adult stroke-related disability is likely …