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Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Prospective Population-Based Cohort Study.

ABSTRACT: Recent genome-wide association studies suggest some overlap of genetic determinants of ischemic stroke (IS) and myocardial infarction (MI). This study aimed to assess shared familial risk between IS and MI in a large, population-wide cohort study.Study participants free of IS and MI and their affected siblings were extracted from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007, forming an exposed sib-pair. They were matched by birth year of both siblings and calendar period to up to five unexposed sib-pairs. Stratified Cox regression analyses were used to assess familial risk of MI and IS in those exposed to having a sibling with IS (n?=?31,659) and MI (n?=?62,766), respectively, compared to unexposed (n?=?143,728 and 265,974).The overall risk of MI when exposed to having a sibling with IS was statistically significantly increased (RR, 1.44; 95% CI, 1.34-1.55, p?

SUBMITTER: Kasiman K

PROVIDER: S-EPMC4668847 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Prospective Population-Based Cohort Study.

Kasiman Katherine K Lundholm Cecilia C Sandin Sven S Malki Ninoa N Sparén Pär P Ingelsson Erik E

Frontiers in cardiovascular medicine 20140730

<h4>Background</h4>Recent genome-wide association studies suggest some overlap of genetic determinants of ischemic stroke (IS) and myocardial infarction (MI). This study aimed to assess shared familial risk between IS and MI in a large, population-wide cohort study.<h4>Methods</h4>Study participants free of IS and MI and their affected siblings were extracted from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007, forming an exposed sib-pair. They were matched by ...[more]

PMID: 26664855

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Project description:Metabolomic approaches in prospective cohorts may offer a unique snapshot into early metabolic perturbations that are associated with a higher risk of cardiovascular diseases (CVD) in healthy people. We investigated the association of 105 serum metabolites, including acylcarnitines, amino acids, phospholipids and hexose, with risk of myocardial infarction (MI) and ischemic stroke in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) and Heidelberg (25,540 adults) cohorts. Using case-cohort designs, we measured metabolites among individuals who were free of CVD and diabetes at blood draw but developed MI (n = 204 and n = 228) or stroke (n = 147 and n = 121) during follow-up (mean, 7.8 and 7.3 years) and among randomly drawn subcohorts (n = 2214 and n = 770). We used Cox regression analysis and combined results using meta-analysis. Independent of classical CVD risk factors, ten metabolites were associated with risk of MI in both cohorts, including sphingomyelins, diacyl-phosphatidylcholines and acyl-alkyl-phosphatidylcholines with pooled relative risks in the range of 1.21-1.40 per one standard deviation increase in metabolite concentrations. The metabolites showed positive correlations with total- and LDL-cholesterol (r ranged from 0.13 to 0.57). When additionally adjusting for total-, LDL- and HDL-cholesterol, triglycerides and C-reactive protein, acyl-alkyl-phosphatidylcholine C36:3 and diacyl-phosphatidylcholines C38:3 and C40:4 remained associated with risk of MI. When added to classical CVD risk models these metabolites further improved CVD prediction (c-statistics increased from 0.8365 to 0.8384 in EPIC-Potsdam and from 0.8344 to 0.8378 in EPIC-Heidelberg). None of the metabolites was consistently associated with stroke risk. Alterations in sphingomyelin and phosphatidylcholine metabolism, and particularly metabolites of the arachidonic acid pathway are independently associated with risk of MI in healthy adults.

Project description:RationalePrevious studies have suggested that acute exacerbations of chronic obstructive pulmonary disease (COPD) may be associated with increased risk of myocardial infarction and ischemic stroke.ObjectivesWe aimed to quantify the increased risks of myocardial infarction and ischemic stroke risk associated with both moderate and severe acute exacerbation, and to investigate factors that may modify these risks.MethodsWe performed a self-controlled case series to investigate the rates of myocardial infarction and ischemic stroke after acute exacerbation compared with stable time, within individuals. The participants were 5,696 adults with COPD with a first myocardial infarction (n = 2,850) or ischemic stroke (n = 3,010) and at least one acute exacerbation from the UK Clinical Practice Research Datalink with linked Hospital Episodes Statistics data.ResultsThe risks of both myocardial infarction and ischemic stroke were increased in the 91 days after an acute exacerbation. The risks were greater after a severe exacerbation (incidence rate ratio [IRR], 2.58; 95% confidence interval [CI], 2.26-2.95 for myocardial infarction; and IRR, 1.97; 95% CI, 1.66-2.33 for ischemic stroke) than after a moderate exacerbation (IRR, 1.58; 95% CI, 1.46-1.71 for myocardial infarction; and IRR, 1.45; 95% CI, 1.33-1.57 for ischemic stroke). The relative risks of myocardial infarction and ischemic stroke associated with acute exacerbation were lower among those with more frequent exacerbations (IRR, 1.42; 95% CI, 1.24-1.62 vs. IRR, 1.69; 95% CI, 1.50-1.91 for myocardial infarction; and IRR, 1.30; 95% CI, 1.15-1.48 vs. IRR, 1.68; 95% CI, 1.50-1.89 for ischemic stroke). Higher GOLD stage was associated with a lower rate of myocardial infarction (IRR, 1.98; 95% CI, 1.61-2.05 vs. IRR, 1.69; 95% CI, 1.45-1.98) but not for ischemic stroke. Aspirin use at baseline was associated with a lower risk of ischemic stroke (IRR, 1.28; 95% CI, 1.10-1.50 vs. IRR, 1.63; 95% CI, 1.47-1.80) but not with myocardial infarction.ConclusionsAcute exacerbations of COPD are associated with an increased risk of myocardial infarction and ischemic stroke within 28 days of their onset. Several patient characteristics were identified that are associated with these events.

Dataset Information

Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Prospective Population-Based Cohort Study.

Publications

Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Prospective Population-Based Cohort Study.

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