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Genetic Risk Factors for Ischemic and Hemorrhagic Stroke.

ABSTRACT: Understanding the genetic risk factors for stroke is an essential step to decipher the underlying mechanisms, facilitate the identification of novel therapeutic targets, and optimize the design of prevention strategies. A very small proportion of strokes are attributable to monogenic conditions, the vast majority being multifactorial, with multiple genetic and environmental risk factors of small effect size. Genome-wide association studies and large international consortia have been instrumental in finding genetic risk factors for stroke. While initial studies identified risk loci for specific stroke subtypes, more recent studies also revealed loci associated with all stroke and all ischemic stroke. Risk loci for ischemic stroke and its subtypes have been implicated in atrial fibrillation (PITX2 and ZFHX3), coronary artery disease (ABO, chr9p21, HDAC9, and ALDH2), blood pressure (ALDH2 and HDAC9), pericyte and smooth muscle cell development (FOXF2), coagulation (HABP2), carotid plaque formation (MMP12), and neuro-inflammation (TSPAN2). For hemorrhagic stroke, two loci (APOE and PMF1) have been identified.

SUBMITTER: Chauhan G

PROVIDER: S-EPMC5086478 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Genetic Risk Factors for Ischemic and Hemorrhagic Stroke.

Chauhan Ganesh G Debette Stéphanie S

Current cardiology reports 20161201 12

Understanding the genetic risk factors for stroke is an essential step to decipher the underlying mechanisms, facilitate the identification of novel therapeutic targets, and optimize the design of prevention strategies. A very small proportion of strokes are attributable to monogenic conditions, the vast majority being multifactorial, with multiple genetic and environmental risk factors of small effect size. Genome-wide association studies and large international consortia have been instrumental ...[more]

PMID: 27796860

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Project description:Background and purposeThe few epidemiological studies that addressed the association between age at menopause and ischemic and hemorrhagic stroke risk in women had conflicting findings. We aimed to investigate whether age at (natural and surgical) menopause is a risk factor for total, ischemic, and hemorrhagic stroke in women.MethodsWe analyzed data from 16 244 postmenopausal women, aged 26 to 70 years at recruitment who were enrolled in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort between 1993 and 1997. Participants were followed for the occurrence of stroke until January 1, 2011. At baseline, participants filled in questionnaires about health, reproductive history including age at menopause, diet, and lifestyle. Cox regression was used to investigate the association between age at menopause and stroke. All analyses were adjusted for age, smoking, systolic blood pressure, and body mass index.ResultsMean age of menopause was 46.4 (7.0) years. A total of 830 strokes (571 ischemic, 162 hemorrhagic, 97 unclassified) were identified. Earlier menopause was associated with an increased risk of total stroke. Compared with women who experienced menopause between 50 and 54 years old, women who underwent menopause before age 40 years had 1.48× higher risk (95% CI, 1.19-1.85) of total stroke. In continuous analyses, we observed a 2% lower total stroke risk for each year menopause was delayed (hazard ratio, 0.98 [95% CI, 0.97-0.99]). The risk between earlier menopause and stroke was confined to ischemic stroke, earlier menopause was not associated with hemorrhagic stroke. The association with age at menopause was stronger for natural menopause (hazard ratio <40 versus 50-54 years, 1.74 [95% CI, 1.12-2.70]) than for surgical menopause (hazard ratio <40 versus 50-54 years, 1.26 [95% CI, 0.84-1.89]).ConclusionsThe risk of total and ischemic stroke decreased with an increase in age at menopause. Whether this should have clinical consequences such as intensified risk factor control should be subject of further studies.

Dataset Information

Genetic Risk Factors for Ischemic and Hemorrhagic Stroke.

Publications

Genetic Risk Factors for Ischemic and Hemorrhagic Stroke.

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