Coronary Artery Disease Risk and Lipidomic Profiles Are Similar in Hyperlipidemias With Family History and Population‐Ascertained Hyperlipidemias
Year: 2019
Type: article
Study design: Observational Study
Abstract: 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.
Authors: Joel T. Rämö, Pietari Ripatti, Rubina Tabassum, Sanni Söderlund, Niina Matikainen, Mathias J. Gerl, Christian Klose, Michal A. Surma, Nathan O. Stitziel, Aki S. Havulinna, Matti Pirinen, Veikko Salomaa, Nelson B. Freimer, Matti Jauhiainen, Aarno Palotie, Marja‐Riitta Taskinen, Kai Simons, Samuli Ripatti
Institutions: University of Helsinki, Institute for Molecular Medicine Finland, HiLIFE – Elämäntieteiden Instituutti, Helsinki University Hospital, Lipotype (Germany), Łukasiewicz Research Network – PORT Polish Center for Technology Development, Washington University in St. Louis, Finnish Institute for Health and Welfare, University of California, Los Angeles, Minerva Foundation, Broad Institute, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Max Planck Institute of Molecular Cell Biology and Genetics, Massachusetts Institute of Technology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,750
OpenAlex ID: W2955937506