Coronary artery disease risk and Lipidomic profiles are similar in hyperlipidemias with family history and population-ascertained Hyperlipidemias

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

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3 Scopus citations

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.

Original languageEnglish
Article numbere012415
JournalJournal of the American Heart Association
Volume8
Issue number13
DOIs
StatePublished - Jul 1 2019

Keywords

  • Coronary artery disease
  • Family study
  • High-risk populations
  • Hypercholesterolemia
  • Hypertriglyceridemia
  • Lipids and lipoproteins

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    Rämö, J. T., Ripatti, P., Tabassum, R., Söderlund, S., Matikainen, N., Gerl, M. J., Klose, C., Surma, M. A., Stitziel, N. O., Havulinna, A. S., Pirinen, M., Salomaa, V., Freimer, N. B., Jauhiainen, M., Palotie, A., Taskinen, M. R., Simons, K., & Ripatti, S. (2019). Coronary artery disease risk and Lipidomic profiles are similar in hyperlipidemias with family history and population-ascertained Hyperlipidemias. Journal of the American Heart Association, 8(13), [e012415]. https://doi.org/10.1161/JAHA.119.012415