Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol.

Autor:	Zhang Y; Division of General Medicine, Columbia University, New York, New York., Dron JS; Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.; Center for Genomic Medicine, Massachusetts General Hospital, Boston., Bellows BK; Division of General Medicine, Columbia University, New York, New York., Khera AV; Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts., Liu J; Department of Population Health Science and Policy, Icahn School of Medicine, Mount Sinai, New York, New York., Balte PP; Division of General Medicine, Columbia University, New York, New York., Oelsner EC; Division of General Medicine, Columbia University, New York, New York., Amr SS; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.; Laboratory for Molecular Medicine, Personalized Medicine, Mass General Brigham, Cambridge, Massachusetts., Lebo MS; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.; Laboratory for Molecular Medicine, Personalized Medicine, Mass General Brigham, Cambridge, Massachusetts., Nagy A; Laboratory for Molecular Medicine, Personalized Medicine, Mass General Brigham, Cambridge, Massachusetts., Peloso GM; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts., Natarajan P; Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Department of Medicine, Massachusetts General Hospital, Boston., Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California., Willer C; Department of Internal Medicine, University of Michigan, Ann Arbor.; Department of Human Genetics, University of Michigan, Ann Arbor.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor., Boerwinkle E; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston., Ballantyne CM; Department of Medicine, Baylor College of Medicine, Houston, Texas., Lutsey PL; Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis., Fornage M; The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston., Lloyd-Jones DM; Northwestern University, Chicago, Illinois., Hou L; Northwestern University, Chicago, Illinois., Psaty BM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle.; Department of Epidemiology, University of Washington, Seattle.; Department of Health Systems and Population Health, University of Washington, Seattle., Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle., Floyd JS; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle.; Department of Epidemiology, University of Washington, Seattle., Vasan RS; The Framingham Heart Study, Framingham, Massachusetts.; Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts.; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts., Heard-Costa NL; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts., Carson AP; Department of Medicine, University of Mississippi Medical Center, Jackson., Hall ME; Department of Medicine, University of Mississippi Medical Center, Jackson., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville., Guo X; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California., Kazi DS; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts., de Ferranti SD; Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts., Moran AE; Division of General Medicine, Columbia University, New York, New York.
Jazyk:	angličtina
Zdroj:	JAMA cardiology [JAMA Cardiol] 2024 Mar 01; Vol. 9 (3), pp. 263-271.
DOI:	10.1001/jamacardio.2023.5366
Abstrakt:	Importance: Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified. Objective: To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults. Design, Setting, and Participants: A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023. Exposures: LDL-C, cumulative past LDL-C, FH variant status. Main Outcomes and Measures: Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults. Results: Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant. Conclusions and Relevance: In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.
Databáze:	MEDLINE
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