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Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography.

ABSTRACT: Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established.In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age <70 years and controls ?70 years without prior MI and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants, and a GRS was calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70, compared with older controls (?70 years of age) with no history of MI (P<0.001). This association was successfully replicated in a second cohort, yielding a pooled P value of <0.001. The GRS modestly improved the area-under-the-curve statistic in models of prevalent MI with traditional risk factors; however, the association was not statistically significant when elderly controls without MI but with s\ angiographic CAD were examined (pooled P=0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort.A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction.

SUBMITTER: Patel RS

PROVIDER: S-EPMC3459582 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography.

Patel Riyaz S RS Sun Yan V YV Hartiala Jaana J Veledar Emir E Su Shaoyong S Sher Salman S Liu Ying X YX Rahman Ayaz A Patel Ronak R Rab S Tanveer ST Vaccarino Viola V Zafari A Maziar AM Samady Habib H Tang W H Wilson WH Allayee Hooman H Hazen Stanley L SL Quyyumi Arshed A AA

Circulation. Cardiovascular genetics 20120705 4

<h4>Background</h4>Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established.<h4>Methods and results</h4>In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age <70 years and controls ≥70 years without prior MI and follow ...[more]

PMID: 22767652

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Project description:Background A risk score for secondary prevention after myocardial infarction (Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention [TRS2P]), based on 9 established clinical factors, was recently developed from the TRA 2°P- TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events) trial. We aimed to evaluate the performance of TRS 2P for predicting long-term outcomes in real-world patients presenting for coronary angiography. Methods and Results A retrospective analysis of 13 593 patients referred to angiography for the assessment or treatment of coronary disease was performed. Risk stratification for 10-year major adverse cardiovascular events was performed using the TRS 2P, divided into 6 categories (0 to ≥5 points), and in relation to the presenting coronary syndrome. All clinical variables, except prior coronary artery bypass grafting, were independent risk predictors. The annualized incidence rate of major adverse cardiovascular events increased in a graded manner with increasing TRS 2P, ranging from 1.65 to 16.6 per 100 person-years ( Ptrend<0.001). Compared with the lowest-risk group (risk indicators=0), the hazard ratios (95% CIs) for 10-year major adverse cardiovascular events were 1.60 (95% CI, 1.36-1.89), 2.58 (95% CI, 2.21-3.02), 4.31 (95% CI, 3.69-5.05), 6.43 (95% CI, 5.47-7.56), and 10.03 (95% CI, 8.52-11.81), in those with 1, 2, 3, 4 and ≥5 risk indicators, respectively. Risk gradation was consistent among individual clinical end points. TRS 2P showed reasonable discrimination with C-statistics of 0.693 for major adverse cardiovascular events and 0.758 for mortality. The graded relationship between the risk score and event rates was observed in both patients presenting with acute and nonacute coronary syndromes. Conclusions The use of TRS 2P, a simple risk score based on routinely collected variables, enables risk stratification in patients undergoing coronary angiography. Its predictive value was demonstrated in a real-world setting with long-term follow-up and regardless of the acuity of coronary presentation.

Project description:BACKGROUND:Among older adults (age ?75 years) hospitalized for acute myocardial infarction, acute kidney injury after coronary angiography is common. Aging-related conditions may independently predict acute kidney injury, but have not yet been analyzed in large acute myocardial infarction cohorts. METHODS:We analyzed data from 2212 participants age ?75 years in the Comprehensive Evaluation of Risk Factors in Older Patients with Acute Myocardial Infarction (SILVER-AMI) study who underwent coronary angiography. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria (serum Cr increase ?0.3 mg/dL from baseline or ?1.5 times baseline). We analyzed the associations of traditional acute kidney injury risk factors and aging-related conditions (activities of daily living impairment, prior falls, cachexia, low physical activity) with acute kidney injury, and then performed logistic regression to identify independent predictors. RESULTS:Participants' mean age was 81.3 years, 45.2% were female, and 9.5% were nonwhite; 421 (19.0%) experienced acute kidney injury. Comorbid diseases and aging-related conditions were both more common among individuals experiencing acute kidney injury. However, after multivariable adjustment, no aging-related conditions were retained. There were 11 risk factors in the final model; the strongest were heart failure on presentation (odds ratio [OR] 1.91; 95% confidence interval [CI], 1.41-2.59), body mass index [BMI] >30 (vs BMI 18-25: OR 1.75; 95% CI, 1.27-2.42), and nonwhite race (OR 1.65; 95% CI, 1.16-2.33). The final model achieved an area under the receiver operating characteristic curve of 0.72 and was well calibrated (Hosmer-Lemeshow P = .50). Acute kidney injury was independently associated with 6-month mortality (OR 1.98; 95% CI, 1.36-2.88) but not readmission (OR 1.26; 95% CI, 0.98-1.61). CONCLUSIONS:Acute kidney injury is common among older adults with acute myocardial infarction undergoing coronary angiography. Predictors largely mirrored those in previous studies of younger individuals, which suggests that geriatric conditions mediate their influence through other risk factors.

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Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography.

Publications

Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography.

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