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  • JAMA September 12, 2017

    Figure 4: Association of Genetic Variants With Naturally Occurring Discordance Between Changes in Concentrations of LDL-C and apoB and the Risk of CHD Among CARDIoGRAMplusC4D Consortium Participants

    Analyses are based on summary data from up to 62 240 participants with coronary heart disease (CHD) and 127 299 control participants from the Coronary Artery DIsease Genome Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) Consortium. Effect sizes are standardized per 10-mg/dL lower level of low-density lipoprotein cholesterol (LDL-C) or 10-mg/dL lower level of apolipoprotein B (apoB). MR-Egger regression estimates are presented for sensitivity analyses. Data markers indicate point estimates of effect; error bars, 95% confidence intervals.
  • JAMA September 12, 2017

    Figure 1: Study Design

    CARDIoGRAMplusC4D indicates Coronary Artery Disease Genome Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; CETP, cholesteryl ester transfer protein; HMGCR, 3-hydroxy-3-methyl-glutaryl-CoA reductase; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
  • JAMA July 25, 2017

    Figure 1: Schematic Diagram of the Mendelian Randomization Assumptions Underpinning a Mendelian Randomization Analysis of the Association Between Serum Calcium Levels and Coronary Artery Disease

    SNPs indicate single-nucleotide polymorphisms. The dashed lines represent potential causal associations between variables that would represent violations of the mendelian randomization assumptions. For a formal treatment of the assumptions, see Greenland.
  • JAMA July 25, 2017

    Figure 3: Mendelian Randomization Estimates of the Association Between Genetically Predicted Serum Calcium Levels and Coronary Artery Disease

    OR indicates odds ratio; SNP, single-nucleotide polymorphisms. Data markers indicate the OR for the association of each calcium-associated SNP with coronary artery disease. Size of the data marker is inversely proportional to variance of the estimate. Error bars indicate 95% CIs.
  • Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction

    Abstract Full Text
    JAMA. 2017; 318(4):371-380. doi: 10.1001/jama.2017.8981

    This analysis evaluates the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease and myocardial infarction using mendelian randomization.

  • JAMA July 25, 2017

    Figure 2: Data Sources and Analysis Plan Using Mendelian Randomization

    BMI indicates body mass index; DIAGRAM, Diabetes Genetics Replication and Meta-analysis; GIANT, Genetic Investigation of Anthropometric Traits; GLGC, Global Lipids Genetics Consortium; ICBP, International Consortium of Blood Pressure; MAGIC, Meta-Analyses of Glucose and Insulin-related traits Consortium; SNPs, single-nucleotide polymorphisms. aFor sample sizes of each study, see Methods.bAny SNP with pleiotropic effects (ie, associated with more than 1 risk factor) violates the Mendelian randomization assumptions. One SNP (rs780094 in the GCKR gene region) had pleiotropic associations with cardiometabolic risk factors and was excluded, leaving 6 calcium-related SNPs for inclusion in the mendelian randomization analyses. cThe estimates for the association of each SNP with coronary artery disease were combined using the inverse-variance weighted method, with summary statistics for coronary artery disease obtained from the CardiogramplusC4D consortium.
  • JAMA March 7, 2017

    Figure 2: Association of Damaging Lipoprotein Lipase Gene (LPL) Mutations With Coronary Artery Disease (CAD) Among 46 891 Individuals in 11 Studies

    In each study, the relationship of rare damaging mutations in LPL with risk of CAD was determined. P values for association tests and confidence intervals were determined using exact methods. A meta-analysis across studies was performed using Cochran-Mantel-Haenszel statistics for stratified 2-by-2 tables. This method combines score statistics and is particularly useful when some observed odds ratios are 0. An odds ratio in the Jackson Heart Study (JHS) cohort was not available (NA) owing to absence of identified carriers of a damaging LPL mutation. ATVB indicates Atherosclerosis, Thrombosis, and Vascular Biology Italian Study; DiscovEHR, DiscovEHR project of the Regeneron Genetics Center and Geisinger Health System; ESP-EOMI, Exome Sequencing Project Early-Onset Myocardial Infarction study; Leicester, Leicester Myocardial Infarction study; North German, North German Myocardial Infarction study; OHS, Ottawa Heart Study; PROCARDIS, Precocious Coronary Artery Disease study; PROMIS, Pakistan Risk of Myocardial Infarction Study; REGICOR, Registre Gironí del COR (Gerona Heart Registry) study; South German, South German Myocardial Infarction study; and dashed line, overall meta-analysis effect estimate.
  • Association of Rare and Common Variation in the Lipoprotein Lipase Gene With Coronary Artery Disease

    Abstract Full Text
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    JAMA. 2017; 317(9):937-946. doi: 10.1001/jama.2017.0972

    This cross-sectional study examines whether rare and common variants in the lipoprotein lipase gene are associated with early-onset coronary artery disease.

  • JAMA February 14, 2017

    Figure 4: Association of 48-SNP Polygenic Risk Score for WHR Adjusted for BMI With Type 2 Diabetes and Coronary Heart Disease

    Results are standardized to a 1-SD increase in waist-to-hip ratio adjusted for body mass index due to polygenic risk score. Estimates were independently derived in genome-wide association studies (CARDIOGRAMplusC4D for coronary heart disease and DIAGRAM for type 2 diabetes) and the UK Biobank. The threshold of significance was P < .025 (0.05/2 = 0.025). Size of data markers is inversely proportional to variance of estimate. CARDIOGRAMplusC4D indicates Coronary Artery DIsease Genome-Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; DIAGRAM, Diabetes Genetics Replication and Meta-analysis.
  • JAMA February 14, 2017

    Figure 2: Study Design

    A polygenic score of 48 single-nucleotide polymorphisms was used as an instrument to estimate the causal association of waist-to-hip ratio (WHR) adjusted for body mass index (BMI) with cardiometabolic quantitative traits, type 2 diabetes, and coronary heart disease; sources of data for analysis included the UK Biobank and publicly available genome-wide association studies. CARDIOGRAMplusC4D indicates Coronary Artery DIsease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; CKDGen, Chronic Kidney Disease Genetics Consortium; DIAGRAM, Diabetes Genetics Replication and Meta-analysis; GIANT, Genetic Investigation of Anthropometric Traits; GLGC, Global Lipids Genetics Consortium; MAGIC, Meta-analyses of Glucose and Insulin-Related Traits Consortium; SNP, single-nucleotide polymorphism.
  • Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial

    Abstract Full Text
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    JAMA. 2016; 316(22):2373-2384. doi: 10.1001/jama.2016.16951

    This randomized clinical trial compares the effects of evolocumab vs placebo on change in percent atheroma volume among adult patients with angiographic coronary disease despite treatment with statins.

  • Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis

    Abstract Full Text
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    JAMA. 2016; 316(20):2126-2134. doi: 10.1001/jama.2016.17020

    This meta-analysis of data from 5 population-based cohort studies assesses the associations between coronary artery calcium (CAC) score and atherosclerotic cardiovascular disease (CVD) in low-risk women and the changes in risk discrimination when CAC score is added to traditional CVD risk factors.

  • JAMA October 4, 2016

    Figure: Association of Low-Density Lipoprotein Cholesterol (LDL-C)–Lowering Genetic Variants With Coronary Artery Disease and Type 2 Diabetes

    Coronary artery disease data are from 60 801 cases with coronary artery disease and 123 504 controls from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) Consortium. Type 2 diabetes data are from 50 775 cases of type 2 diabetes and 270 269 controls from European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study, the UK Biobank study, and the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM). In addition to the EPIC-InterAct study, the UK Biobank study, and DIAGRAM, type 2 diabetes association analyses of rs12916 at HMGCR included 11 studies (4496 cases and 50 677 controls) previously reported by Swerdlow et al. Therefore, the sample size of HMGCR genetic variants association with type 2 diabetes was 55 271 cases of type 2 diabetes and 320 946 controls. All results are scaled to represent the odds ratio per 1-mmol/L (38.7-mg/dL) genetically predicted reduction in LDL-C.
  • Association Between Low-Density Lipoprotein Cholesterol–Lowering Genetic Variants and Risk of Type 2 Diabetes: A Meta-analysis

    Abstract Full Text
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    JAMA. 2016; 316(13):1383-1391. doi: 10.1001/jama.2016.14568

    This meta-analysis of genetic association studies summarizes associations between molecular targets of lipid-lowering therapy and risk of type 2 diabetes and coronary artery disease.

  • Exercise Treadmill Testing

    Abstract Full Text
    JAMA. 2015; 314(18):1968-1969. doi: 10.1001/jama.2015.11719

    A 53-year-old man with chest pain and treated hypertension undergoes an exercise treadmill test, which demonstrates 1.5-mm ST-segment depression in inferolateral leads during recovery. How do you interpret the test result?

  • JAMA July 14, 2015

    Figure 2: Comparison of Statin Eligibility by 2004 ATP III Guidelines vs 2013 ACC/AHA Guidelines Across CAC Score Strata

    ACC/AHA, American College of Cardiology/American Heart Association; ATP III, Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; CAC, coronary artery calcification.
  • Association Between Physician Time-Unlimited vs Time-Limited Internal Medicine Board Certification and Ambulatory Patient Care Quality

    Abstract Full Text
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    JAMA. 2014; 312(22):2358-2363. doi: 10.1001/jama.2014.13992

    This retrospective analysis reports that there were no significant differences between physicians with time-limited vs time-unlimited board certification on 10 primary care performance measures.

  • Effect of Screening for Coronary Artery Disease Using CT Angiography on Mortality and Cardiac Events in High-Risk Patients With Diabetes: The FACTOR-64 Randomized Clinical Trial

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    JAMA. 2014; 312(21):2234-2243. doi: 10.1001/jama.2014.15825

    This randomized clinical trial reports that use of coronary computed tomography angiography to screen for coronary artery disease is not supported among asymptomatic patients with type 1 or type 2 diabetes.

  • Optimal Medical Therapy vs CT Angiography Screening for Patients With Diabetes

    Abstract Full Text
    JAMA. 2014; 312(21):2219-2220. doi: 10.1001/jama.2014.15958

    This Viewpoint discusses the use of screening coronary computed tomographic angiography in asymptomatic patients with diabetes.

  • Revascularization in Stable Coronary Artery Disease

    Abstract Full Text
    JAMA. 2014; 312(19):2028-2029. doi: 10.1001/jama.2014.9314