Dataset Information

KIF6 p.Trp719Arg Testing to Assess Risk of Coronary Artery Disease and/or Statin Response.

ABSTRACT: Coronary artery disease (CAD) is a leading cause of death worldwide and in the United States it is responsible for more than 500,000 deaths each year. Genome-wide association studies (GWAS) have revealed connections between a number of common single nucleotide polymorphisms (SNPs) and CAD and other cardiovascular diseases. The p.Trp719Arg SNP in the kinesin-like family 6 (KIF6) gene has recently been reported as a potential risk factor for CAD as well as a predictor of response to statin therapy.

SUBMITTER: Allingham-Hawkins D

PROVIDER: S-EPMC2959200 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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KIF6 p.Trp719Arg Testing to Assess Risk of Coronary Artery Disease and/or Statin Response.

Allingham-Hawkins Diane D Lea Andrew A Levine Susan S

PLoS currents 20101021

Coronary artery disease (CAD) is a leading cause of death worldwide and in the United States it is responsible for more than 500,000 deaths each year. Genome-wide association studies (GWAS) have revealed connections between a number of common single nucleotide polymorphisms (SNPs) and CAD and other cardiovascular diseases. The p.Trp719Arg SNP in the kinesin-like family 6 (KIF6) gene has recently been reported as a potential risk factor for CAD as well as a predictor of response to statin therapy ...[more]

PMID: 20975779

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Project description:ObjectivesThis study sought to determine prognostic value of nonobstructive coronary artery disease (CAD) for atherosclerotic cardiovascular disease (ASCVD) events and to determine whether incorporation of this information into the pooled cohort equation reclassifies recommendations for statin therapy as defined by the 2013 guidelines for cholesterol management of the American College of Cardiology and American Heart Association (ACC/AHA).BackgroundDetection of nonobstructive CAD by coronary computed tomography angiography may improve risk stratification and permit individualized and more appropriate allocation of statin therapy.MethodsThis study determined the pooled hazard ratio of nonobstructive CAD for ASCVD events from published studies and incorporated this information into the ACC/AHA pooled cohort equation. The study calculated revised sex- and ethnicity-based 10-year ASCVD risk and determined boundaries corresponding to the original 7.5% risk for ASCVD events. It also assessed reclassification for statin eligibility by incorporating the results from meta-analysis to individual patients from a separate cohort.ResultsThis study included 2 studies (2,295 subjects; 66% male; prevalence of nonobstructive CAD, 47%; median follow-up, 49 months; 67 ASCVD events). The hazard ratio of nonobstructive CAD for ASCVD events was 3.2 (95% confidence interval: 1.5 to 6.7). Incorporation of this information into the pooled cohort equation resulted in reclassification toward statin eligibility in individuals with nonobstructive CAD, with an original ASCVD score of 3.0% and 5.9% or higher in African-American women and men and a score of 4.4% and 4.6% or higher in Caucasian women and men, respectively. The absence of nonobstructive CAD resulted in reclassification toward statin ineligibility if the original ASCVD score was as 10.0% and 17.9% or lower in African-American women and men and 13.7% and 14.3% or lower in Caucasian women and men, respectively. Reclassification is observed in 14% of patients.ConclusionsDetection of nonobstructive CAD by coronary computed tomography angiography improves risk stratification and permits individualized and more appropriate allocation of statin therapy across sex and ethnicity groups.

Project description:BackgroundThe Multi-Ethnic Study of Atherosclerosis (MESA) showed that the addition of coronary artery calcium (CAC) to traditional risk factors improves risk classification, particularly in intermediate risk asymptomatic patients with LDL cholesterol levels <160 mg/dL. However, the cost-effectiveness of incorporating CAC into treatment decision rules has yet to be clearly delineated.ObjectiveTo model the cost-effectiveness of CAC for cardiovascular risk stratification in asymptomatic, intermediate risk patients not taking a statin. Treatment based on CAC was compared to (1) treatment of all intermediate-risk patients, and (2) treatment on the basis of United States guidelines.MethodsWe developed a Markov model of first coronary heart disease (CHD) and cardiovascular disease (CVD) events. We modeled statin treatment in intermediate risk patients with CAC≥1 and CAC≥100, with different intensities of statins based on the CAC score. We compared these CAC-based treatment strategies to a "treat all" strategy and to treatment according to the Adult Treatment Panel III (ATP III) guidelines. Clinical and economic outcomes were modeled over both five- and ten-year time horizons. Outcomes consisted of CHD and CVD events and Quality-Adjusted Life Years (QALYs). Sensitivity analyses considered the effect of higher event rates, different CAC and statin costs, indirect costs, and re-scanning patients with incidentalomas.ResultsWe project that it is both cost-saving and more effective to scan intermediate-risk patients for CAC and to treat those with CAC≥1, compared to treatment based on established risk-assessment guidelines. Treating patients with CAC≥100 is also preferred to existing guidelines when we account for statin side effects and the disutility of statin use.ConclusionCompared to the alternatives we assessed, CAC testing is both effective and cost saving as a risk-stratification tool, particularly if there are adverse effects of long-term statin use. CAC may enable providers to better tailor preventive therapy to patients' risks of CVD.

Dataset Information

KIF6 p.Trp719Arg Testing to Assess Risk of Coronary Artery Disease and/or Statin Response.

Publications

KIF6 p.Trp719Arg Testing to Assess Risk of Coronary Artery Disease and/or Statin Response.

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