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J Am Heart Assoc. 2019 Jul 2;8(13):e012415. doi: 10.1161/JAHA.119.012415. Epub 2019 Jun 29.

Coronary Artery Disease Risk and Lipidomic Profiles Are Similar in Hyperlipidemias With Family History and Population-Ascertained Hyperlipidemias.

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1 Institute for Molecular Medicine Finland HiLIFE University of Helsinki Finland.
2 Research Programs Unit Clinical and Molecular Metabolism University of Helsinki Finland.
3 Endocrinology Abdominal Center Helsinki University Hospital Helsinki Finland.
4 Lipotype GmbH Dresden Germany.
5 Łukasiewicz Research Network-PORT Polish Center for Technology Development Wroclaw Poland.
6 Cardiovascular Division Department of Medicine Washington University School of Medicine St. Louis MO.
7 Department of Genetics Washington University School of Medicine St. Louis MO.
8 McDonnell Genome Institute Washington University School of Medicine St. Louis MO.
9 National Institute for Health and Welfare Helsinki Finland.
10 Department of Mathematics and Statistics Faculty of Science University of Helsinki Finland.
16 Department of Public Health Clinicum Faculty of Medicine University of Helsinki Finland.
11 Center for Neurobehavioral Genetics Semel Institute for Neuroscience and Human Behavior University of California Los Angeles CA.
12 Minerva Foundation Institute for Medical Research Biomedicum Helsinki Finland.
13 Program in Medical and Population Genetics and The Stanley Center for Psychiatric Research The Broad Institute of MIT and Harvard Cambridge MA.
14 Psychiatric and Neurodevelopmental Genetics Unit Department of Psychiatry, Analytic and Translational Genetics Unit Department of Medicine, and the Department of Neurology Massachusetts General Hospital Boston MA.
15 Max Planck Institute of Cell Biology and Genetics Dresden Germany.


Background We asked whether, after excluding familial hypercholesterolemia, individuals with high low-density lipoprotein cholesterol ( LDL -C) or triacylglyceride levels and a family history of the same hyperlipidemia have greater coronary artery disease risk or different lipidomic profiles compared with population-based hyperlipidemias. Methods and Results We determined incident coronary artery disease risk for 755 members of 66 hyperlipidemic families (≥2 first-degree relatives with similar hyperlipidemia) and 19 644 Finnish FINRISK population study participants. We quantified 151 circulating lipid species from 550 members of 73 hyperlipidemic families and 897 FINRISK participants using mass spectrometric shotgun lipidomics. Familial hypercholesterolemia was excluded using functional LDL receptor testing and genotyping. Hyperlipidemias ( LDL -C or triacylglycerides >90th population percentile) associated with increased coronary artery disease risk in meta-analysis of the hyperlipidemic families and the population cohort (high LDL -C: hazard ratio, 1.74 [95% CI, 1.48-2.04]; high triacylglycerides: hazard ratio, 1.38 [95% CI, 1.09-1.74]). Risk estimates were similar in the family and population cohorts also after adjusting for lipid-lowering medication. In lipidomic profiling, high LDL -C associated with 108 lipid species, and high triacylglycerides associated with 131 lipid species in either cohort (at 5% false discovery rate; P-value range 0.038-2.3×10-56). Lipidomic profiles were highly similar for hyperlipidemic individuals in the families and the population ( LDL -C: r=0.80; triacylglycerides: r=0.96; no lipid species deviated between the cohorts). Conclusions Hyperlipidemias with family history conferred similar coronary artery disease risk as population-based hyperlipidemias. We identified distinct lipidomic profiles associated with high LDL -C and triacylglycerides. Lipidomic profiles were similar between hyperlipidemias with family history and population-ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms.


coronary artery disease; family study; high‐risk populations; hypercholesterolemia; hypertriglyceridemia; lipids and lipoproteins

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