Background: Knowledge about the classic risk and protective factors of ischemic stroke is accumulating, but the underlying pathogenesis has not yet been fully understood. As emerging evidence indicates that DNA methylation plays a role in the pathological process of cerebral ischemia, this study aims to summarize the evidence of the association between DNA methylation and ischemic stroke. Methods: MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials were searched for eligible studies. The results reported by each study were summarized narratively. Results: A total of 20 studies with 7,014 individuals finally met the inclusion criteria. Three studies focused on global methylation, 11 studies on candidate-gene methylation, and six on epigenome-wide methylation analysis. Long-interspersed nuclear element 1 was found to be hypomethylated in stroke cases in two studies. Another 16 studies reported 37 genes that were differentially methylated between stroke cases and controls. Individuals with ischemic stroke were also reported to have higher acceleration in Hanuum 's epigenetic age compared to controls. Conclusion: DNA methylation might be associated with ischemic stroke and play a role in several pathological pathways. It is potentially a promising biomarker for stroke prevention, diagnosis and treatment, but the current evidence is limited by sample size and cross-sectional or retrospective design. Therefore, studies on large asymptomatic populations with the prospective design are needed to validate the current evidence, explore new pathways and identify novel risk/protective loci.

Haemoglobin A1c (HbA1c) is a marker of glycaemic control in type 2 diabetes mellitus (T2DM). Increased waist circumference (WC) is known to be associated with T2DM. Therefore, we investigated the relationship of WC with HbA1c and explored its optimal cutoff for identifying prediabetes and diabetes risk. This study included 2339 participants between 18 and 84 years of age [mean (SD) age, 43.5 (11.9) years] with valid data on WC, HbA1c and related variables in the Shenzhen–Hong Kong United Network on Cardiovascular Disease study. Participants on anti-diabetic medications were excluded. Multiple linear regression was used to investigate the relationship between HbA1c and WC. Cutoff values of WC indicating an HbA1c level of 5.7% and 6.5% were also assessed using optimal binning. There was a significant linear relationship between WC and HbA1c in the overall population (B = 0.261, P < 0.001), men (B = 0.206, P < 0.001) and women (B = 0.311, P < 0.001). After adjustment for smoking, alcohol consumption, physical activity, hypertension, hypercholesterolaemia and age, the association remained significant in the overall population (B = 0.201, P < 0.001), men (B = 0.186, P < 0.001) and women (B = 0.182, P < 0.001). The optimal cutoff values of WC indicating an HbA1c level of 5.7% and 6.5% was 83 cm (entropy = 0.943) and 85 cm (entropy = 0.365) in men, and 78 cm (entropy = 0.922) and 86 cm (entropy = 0.256) in women. The linear relationship between WC and HbA1c in this study suggests that addressing central obesity issue is beneficial to people with T2DM or at risk of T2DM. WC cutoff values of 85 cm for men and 86 cm for women are appropriate for recommendation to undergo diabetes screening.

BackgroundIncreasing evidence indicated that infection factors play important roles in stroke development. Human cytomegalovirus (HCMV) infection was positively associated with atherosclerosis and hypertension which are stroke risk factors. Therefore, we aimed to explore the relationship between HCMV infection and stroke using the data of US National Health and Nutrition Examination Survey (NHANES).MethodsWe analysed data on 2844 men and 3257 women in the NHANES 1999–2004. We included participants aged 20–49 years who had valid data on HCMV infection and stroke.Results54.1% of participants had serological evidence of HCMV infection and 0.8% of them had a previous diagnosis of stroke. There were ethnic differences in the prevalence of HCMV seropositivity (p<0.001). There was no significant association between HCMV seropositivity and stroke in men in any of the models. In women, HCMV seropositivity was associated with stroke before adjustment (OR=3.45, 95% CI 1.09 to 10.95, p=0.036). After adjusting for race/ethnicity, the association remained significant (OR=4.40, 95% CI 1.37 to 14.09, p=0.014). After further adjustment for body mass index, diabetes, hypercholesterolaemia, hypertension, alcohol consumption, smoking and physical activity, the association still existed (OR=3.58, 95% CI 1.14 to 11.25, p=0.030). The association was significant consistently in adjusted model for age (OR=3.39, 95% CI 1.08 to 10.64, p=0.037).ConclusionsWe found a strong association between HCMV and stroke in women from the nationally representative population-based survey. This provide additional motivation for undertaking the difficult challenge to reduce the prevalence of stroke.