Familial History of Stroke Is Associated With Acute Coronary Syndromes in Women

Banerjee, Amitava; Lim, C.C.S.; Silver, L E; Welch, Sarah; Banning, Adrian P.; Rothwell, Peter M.

doi:10.1161/circgenetics.110.957688

Cited by 32 publications

(23 citation statements)

References 36 publications

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“…25,26 Existing research is however based on the associated risk in populations with a higher mean age and thus older parents, and our population might be too young to demonstrate any such association.…”

Section: Discussionmentioning

confidence: 87%

Prepregnancy Obesity and Associations With Stroke and Myocardial Infarction in Women in the Years After Childbirth

et al. 2014

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A disturbingly low rate of temporal decline in coronary heart disease mortality has been observed among women aged 35-44 years, compared with men and older women. 1 Additionally, women aged <45 years have an adverse prognosis after myocardial infarction as compared with men and older women, 2 and women 31-50 years old have a poorer prognosis than men after ischemic stroke.3 Further insight into cardiovascular risk factors and the prognosis of cardiovascular disease in young women is warranted, as requested by leading healthcare organizations including the American Heart Association. Clinical Perspective on p 337The World Health Organization states obesity to be the fifth leading cause of global death, 5 and the consequences of obesity has been found to have a higher impact in younger women (≤65 years of age) than in older women. 6 A recent report from the American Heart Association has furthermore documented that the rise in prevalent obesity is alarmingly rapid in the young.7 Despite the rising concerns regarding the obesity epidemic and the identification of young women as an overlooked group with a high morbidity after cardiovascular events, the association between obesity and the risk of cardiovascular disease in the young women has yet to be determined.We examined the associations between prepregnancy body mass index (BMI) and the risk of stroke and myocardial infarction in young, healthy women who have given birth in a nationwide study including pregnancy-associated risk factors in addition to well-established cardiovascular risk factors.Background-Cardiovascular events (stroke or myocardial infarction) are often associated with poorer prognosis in younger, compared with older individuals. We examined the associations between prepregnancy obesity and the risks of myocardial infarction and stroke in young, healthy women. ). The hazard ratios of myocardial infarction, ischemic stroke, and a composite outcome (myocardial infarction, stroke, cardiovascular death) were assessed using multivariable Cox regression models. We included 273 101 women with a median age of 30.4 years (interquartile range, 27.2-33.8). A total of 68 women experienced a myocardial infarction, and 175 women experienced an ischemic stroke. The adjusted hazard ratios of myocardial infarction compared with normal weight were 2.50 (95% confidence interval [95% CI], 0.97-6.50) in underweight, 1.68 (95% CI, 0.92-3.06) in overweight, and 2.63 (95% CI, 1.41-4.91) in obese women. For ischemic stroke the adjusted hazard ratios were 1.06 (95% CI, 0.44-2.28) in underweight, 1.27 (95% CI, 0.87-1.85) in overweight, and 1.89 (95% CI, 1.25-2.84) in obese women, respectively. For the composite outcome, hazard ratios were 1.34 (95% CI, 0.81-2.20), 1.43 (95% CI, 1.11-1.84), and 1.76 (95% CI, 1.31-2.34) for underweight, overweight, and obese women. Conclusions-In apparently healthy women of fertile age, prepregnancy obesity was associated with increased risks of ischemic stroke and myocardial infarction in the years after childbirth. (Circulation. 2014;129:...

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Section: Discussionmentioning

confidence: 87%

Prepregnancy Obesity and Associations With Stroke and Myocardial Infarction in Women in the Years After Childbirth

et al. 2014

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“…4, 5 Twin and family studies have demonstrated that both IS and CAD are highly heritable 6, 7 with some evidence of a shared heritability for both diseases. 8 …”

Section: Introductionmentioning

confidence: 99%

Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease

Dichgans

Malik

König

et al. 2014

Stroke

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307

224

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Summary Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each have a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Methods Genome-wide association data were obtained from the METASTROKE, CARDIoGRAM, and C4D consortia. We first analyzed common variants reaching a nominal threshold of significance (p<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2,167 individuals with the ischemic large artery stroke (LAS) subtype. Results Common variants associated with CAD at p<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, three and five loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (p<5×10-8) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Since these loci had prior evidence for genome-wide significance for CAD we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (pIS=1.62×10-07) and ABO (pIS =2.6×10-4) as well as at HDAC9 (pLAS=2.32×10-12), 9p21 (pLAS =3.70×10-6), RAI1-PEMT-RASD1 (pLAS =2.69×10-5), EDNRA (pLAS =7.29×10-4), and CYP17A1-CNNM2-NT5C2 (pLAS =4.9×10-4). Conclusions Our results demonstrate substantial overlap in the genetic risk of ischemic stroke and particularly the large artery stroke subtype with coronary artery disease.

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“…3 These data also indicate that stroke and coronary artery disease share genetic factors, as a family history of coronary artery disease is associated with an increased risk of large-artery stroke, 5 and a family history of stroke is associated with acute coronary syndrome. 6 Furthermore, a family history of stroke is also strongly associated with risk factors for stroke, such as hypertension and diabetes mellitus, which makes it important to determine whether any identified genetic factors predispose patients to stroke indirectly via risk factors, or independently of the risk factors. 7 Sex differences have also been reported: women were found to be approximately 50% more likely to have a maternal history of stroke than a paternal history of stroke, whereas no similar excess exists in men.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and treatment of ischaemic stroke—insights from genetic associations

Markus

Bevan

2014

Nat Rev Neurol

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| The precise pathophysiology of ischaemic stroke is unclear, and a greater understanding of the different mechanisms that underlie large-artery, cardioembolic and lacunar ischaemic stroke subtypes would enable the development of more-effective, subtype-specific therapies. Genome-wide association studies (GWASs) are identifying novel genetic variants that associate with the risk of stroke. These associations provide insight into the pathophysiological mechanisms, and present opportunities for novel therapeutic approaches. In this Review, we summarize the genetic variants that have been linked to ischaemic stroke in GWASs to date and discuss the implications of these associations for both our understanding and treatment of ischaemic stroke. The majority of genetic variants identified are associated with specific subtypes of ischaemic stroke, implying that these subtypes have distinct genetic architectures and pathophysiological mechanisms. The findings from the GWASs highlight the need to consider whether therapies should be subtype-specific. Further GWASs that include large cohorts are likely to provide further insights, and emerging technologies will complement and build on the GWAS findings.

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Familial History of Stroke Is Associated With Acute Coronary Syndromes in Women

Cited by 32 publications

References 36 publications

Prepregnancy Obesity and Associations With Stroke and Myocardial Infarction in Women in the Years After Childbirth

Prepregnancy Obesity and Associations With Stroke and Myocardial Infarction in Women in the Years After Childbirth

Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease

Mechanisms and treatment of ischaemic stroke—insights from genetic associations

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