Single nucleotide polymorphisms associated with coronary heart disease predict incident ischemic stroke in the atherosclerosis risk in communities study.
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ABSTRACT:
SUBMITTER: Morrison AC
PROVIDER: S-EPMC2662496 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeEpidemiological studies have documented that plasma d-dimer, a fibrin degradation product, is a risk marker for coronary heart disease, but there is limited prospective evidence for stroke. Given that thrombosis is a key mechanism for many strokes, we studied whether d-dimer is a risk marker for ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsWe measured d-dimer in 11 415 ARIC participants free of stroke and coronary heart disease in 1992 to 1995. We followed them for stroke, stroke subtype, and coronary heart disease events through 2012.ResultsOver a median of 18 years of follow-up, 719 participants had incident strokes (628 ischemic and 91 hemorrhagic). d-dimer was associated positively with risk of total, ischemic, and cardioembolic strokes, with risk elevated primarily for the highest quintile of d-dimer. After adjustment for other cardiovascular risk factors, the hazard ratio for the highest versus lowest quintile of d-dimer was 1.30 (95% confidence interval, 1.02-1.67) for total stroke, 1.33 (95% confidence interval, 1.02-1.73) for ischemic stroke, and 1.79 (95% confidence interval, 1.08-2.95) for cardioembolic stroke. There was no association with hemorrhagic, lacunar, or nonlacunar stroke categories. d-dimer was positively but weakly associated with coronary heart disease incidence.ConclusionsA higher basal plasma d-dimer concentration in the general population is a risk marker for ischemic stroke, especially cardioembolic stroke.
| S-EPMC4696899 | biostudies-literature
Project description:Ultrasound measurements of arterial stiffness are associated with atherosclerosis risk factors, but limited data exist on their association with incident cardiovascular events. We evaluated the association of carotid ultrasound-derived arterial stiffness measures with incident coronary heart disease (CHD) and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.Carotid arterial strain and compliance, distensibility and stiffness indices, pressure-strain, and Young elastic moduli were measured in 10 407 individuals using ultrasound. Hazard ratios for incident CHD (myocardial infarction, fatal CHD, coronary revascularization) and stroke in minimally adjusted (age, sex, center, race) and fully adjusted models (minimally adjusted model+diabetes, height, weight, total cholesterol, high-density lipoprotein cholesterol, tobacco use, systolic blood pressure, antihypertensive medication use, and carotid intima-media thickness) were calculated.The mean age was 55.3 years. Over a mean follow-up of 13.8 years, 1267 incident CHD and 383 ischemic stroke events occurred. After full adjustment for risk factors and carotid intima-media thickness, all arterial stiffness parameters (carotid arterial strain hazard ratio [HR], 1.14 [95% CI, 1.02-1.28]; arterial distensibility HR, 1.19 [1.02-1.39]; stiffness indices HR, 1.14 [1.04-1.25]; pressure-strain HR, 1.17 [1.06-1.28]; Young elastic moduli HR, 1.13 [1.03-1.24]), except arterial compliance (HR, 1.02 [0.90-1.16], were significantly associated with incident stroke but not with CHD.After adjusting for cardiovascular risk factors, ultrasound measures of carotid arterial stiffness are associated with incident ischemic stroke but not incident CHD events despite that the 2 outcomes sharing similar risk factors.URL: www.clinicaltrials.gov. Unique identifier: NCT00005131.
| S-EPMC3246524 | biostudies-literature
Project description:Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with increased all-cause and cardiovascular mortality. We examined the association between reduced HRV and incident stroke in a community-based cohort.The Atherosclerosis Risk in Communities (ARIC) study measured HRV using 2-minute ECG readings in 12 550 middle-aged adults at baseline (1987-1989). HRV indices were calculated using the SD of RR intervals (SDNN), the mean of all normal RR intervals (meanNN), the root mean square of successive differences of successive RR intervals (RMSSD), low (LF) and high (HF) frequency power, and the LF/HF ratio. All HRV measures were categorized into quintiles. Incident stroke was adjudicated through 2011. Cox regression was used to estimate hazard ratios (HRs) with the lowest HRV quintile as the reference, with and without stratification by prevalent diabetes mellitus.Over a median follow-up of 22 years, 816 (6.5%) participants experienced incident stroke. After covariate adjustment, there was no strong evidence of association between HRV and stroke risk. In stratified analyses, the lowest HRV quintile was associated with higher stroke risk compared with the highest quintile for SDNN (HR, 2.0, 95% confidence interval, 1.1-4.0), RMSSD (HR, 1.7; 95% confidence interval, 0.9-3.2), LF (HR, 1.5; 95% confidence interval, 0.8-3.0), and HF (HR, 1.7; 95% confidence interval, 0.9-3.0) only among people with diabetes mellitus.Lower HRV was associated with higher risk of incident stroke among middle-aged adults with prevalent diabetes mellitus but not among people without diabetes mellitus.
| S-EPMC4880420 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. METHODS:A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. RESULTS:SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. CONCLUSIONS:We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted.
| S-EPMC4174726 | biostudies-literature
Project description:BACKGROUND:The association of individual fatty acids with ischemic stroke has not been thoroughly studied, and results have been inconsistent. Few prospective studies have systematically explored the association of biomarkers of fatty acid intake with stroke. The aim of this study was to explore which individual plasma fatty acids would be associated with higher risk of ischemic stroke among whites. METHODS:We studied 3,870 white men and women from the Minneapolis field center of the Atherosclerosis Risk in Communities (ARIC) Study, aged 45-64 years at baseline (1987-1989), who had plasma cholesterol ester (CE) and phospholipid (PL) fatty acids measured. Participants were followed through 2008 for incident ischemic stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) across quartiles of each fatty acid, measured as the percentage of total fatty acids, were calculated using the Cox proportional hazards model. RESULTS:During a maximum of 22 years of follow-up, we identified 168 cases of ischemic stroke. After adjustment for age and sex, plasma levels of saturated fatty acids were associated positively: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.93 (1.23-3.04, p for trend = 0.01) and that for PL fraction was 1.64 (1.05-2.57, p for trend = 0.03). There was also a positive linear association with monounsaturated fatty acids, especially with palmitoleic acid: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.86 (1.20-2.87, p for trend = 0.003) and that for PL fraction was 1.52 (0.99-2.34, p for trend = 0.005). No associations of ?-3 and ?-6 polyunsaturated fatty acids with ischemic stroke were observed, but linoleic acid was inversely and nonlinearly associated with ischemic stroke: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 0.64 (0.43-0.97, p for trend = 0.13) and that for PL fraction was 0.69 (0.45-1.05, p for trend = 0.24). These associations were generally unchanged after adjustment for cardiovascular risk factors. CONCLUSIONS:In this US cohort of whites, we found significant positive associations of plasma saturated and monounsaturated fatty acids, especially of palmitoleic acid, with ischemic stroke. We also found an inverse nonlinear association between linoleic acid and ischemic stroke.
| S-EPMC3875134 | biostudies-literature
Project description:ObjectiveThe cytochromes P450 epoxygenases CYP2J2 and CYP2C8 synthesize epoxyeicosatrienoic acids, which regulate endothelial function. We sought to determine if genetic variation in CYP2J2 and CYP2C8 was associated with coronary heart disease risk.MethodsWe genotyped 2065 Atherosclerosis Risk in Communities study participants (1085 incident coronary heart disease cases, 980 noncases) for polymorphisms in CYP2J2 and CYP2C8. Using a case-cohort design, associations between genotype and incident coronary heart disease risk were evaluated using proportional hazards regression. The influence of cigarette smoking on these associations was also evaluated. False discovery rate q-values were estimated to minimize the impact of the multiple statistical comparisons completed. All analyses were race stratified.ResultsThe CYP2J2 G-50T polymorphism variant -50T allele was associated with significantly lower risk of incident coronary heart disease in African-Americans (adjusted hazard rate ratio 0.58, 95% confidence interval 0.35-0.96, P=0.036, q=0.051); however, no significant association was observed in Caucasians. Overall, the I264M, I269F, and K399R polymorphisms in CYP2C8 were not significantly associated with risk of incident coronary heart disease. In Caucasians, the relationship between the I264M and K399R polymorphisms and incident coronary heart disease risk was significantly modified by cigarette smoking status (P for interaction=0.008, q=0.064), with the highest risk observed in smokers carrying at least one variant allele.ConclusionsThe G-50T polymorphism in CYP2J2 may be an important risk factor for the development of coronary heart disease events in African-Americans, whereas cigarette smoking may modify the relationship between the I264M and K399R polymorphisms in CYP2C8 and coronary heart disease risk in Caucasians. Confirmation of these findings in an independent population is warranted.
| S-EPMC1947003 | biostudies-literature
Project description:In 2007, the Wellcome Trust Case Control Consortium (WTCCC) performed a genome-wide association study in 2,000 British coronary heart disease (CHD) cases and 3,000 controls after genotyping 469,557 single nucleotide polymorphisms (SNPs). Seven variants associated with CHD were initially identified, and 5 SNPs were later found in replication studies. In the current study, the authors aimed to determine whether the 12 SNPs reported by the WTCCC predicted incident CHD through 2004 in a biracial, prospective cohort study (Atherosclerosis Risk in Communities) comprising 15,792 persons aged 45-64 years who had been selected by probability sampling from 4 different US communities in 1987-1989. Cox proportional hazards models with adjustment for age and gender were used to estimate CHD hazard rate ratios (HRRs) over a 17-year period (1,362 cases in whites and 397 cases in African Americans) under an additive genetic model. The results showed that 3 SNPs in whites (rs599839, rs1333049, and rs501120; HRRs were 1.10 (P = 0.044), 1.14 (P < 0.001), and 1.14 (P = 0.030), respectively) and 1 SNP in African Americans (rs7250581; HRR = 1.60, P = 0.05) were significantly associated with incident CHD. This study demonstrates that genetic variants revealed in a case-control genome-wide association study enriched for early disease onset may play a role in the genetic etiology of CHD in the general population.
| S-EPMC2800304 | biostudies-literature
Project description:This study was designed to assess the relationship between insulin resistance and incident heart failure (HF) in a community-based cohort.Diabetes mellitus increases the risk for HF, but the association between insulin resistance and HF in individuals without diabetes is unclear.We prospectively analyzed 12,606 participants without diabetes mellitus, prevalent HF, or history of myocardial infarction at baseline (1987 to 1989) from the ARIC (Atherosclerosis Risk in Communities) study. We assessed the relationship between insulin resistance and incident HF using the homeostatic model assessment of insulin resistance (HOMA-IR) equation, adjusting for age, sex, race, body mass index, smoking, hypertension, center, and interim myocardial infarction. We tested for interactions by age, sex, obesity, and race.Participants with insulin resistance, defined as HOMA-IR ≥2.5 (n = 4,810, 39%), were older, more likely female, African American, hypertensive, and had a higher body mass index as compared with those without insulin resistance. There were 1,455 incident HF cases during a median of 20.6 years of follow-up. Insulin resistance defined by this threshold was not significantly associated with an increased risk for incident HF after adjustment (hazard ratio: 1.08, 95% confidence interval: 0.95 to 1.23). However, when analyzed continuously, this relationship was nonlinear, which indicated that risk increased, and was significantly associated with incident HF between HOMA-IR of 1.0 to 2.0, adjusting for baseline covariates; however, values over 2.5 were not associated with additional increased risk in adjusted models.In a community cohort, insulin resistance, defined by lower levels of HOMA-IR than previously considered, was associated with an increased risk for HF.
| S-EPMC3893700 | biostudies-other
Project description: Not available
| S-EPMC2656439 | biostudies-literature
Project description:BACKGROUND:Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients. METHODOLOGY/PRINCIPAL FINDINGS:We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ?50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR?=?1.29 [1.09-1.53]; p?=?0.003). This association was strong and significant in T2DM patients (n?=?393; OR?=?1.91 [1.32-2.75]; p?=?0.001) but not in non-diabetic subjects (OR?=?1.09 [0.90-1.33]; p?=?0.370). The interaction risk allele by T2DM was significant (p(interaction)?=?0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR?=?1.90 [1.31-2.74]; p?=?0.001 and OR?=?1.75 [1.22-2.50]; p?=?0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR?=?1.22 [1.04-1.43]; p?=?0.013 and OR?=?1.67 [1.19-2.22]; p?=?0.003, respectively). CONCLUSIONS/SIGNIFICANCE:These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis.
| S-EPMC3058059 | biostudies-literature