Audrey Y Chu1, Franco Giulianini2, Bryan J Barratt2, Bo Ding2, Fredrik Nyberg2, Samia Mora2, Paul M Ridker2, Daniel I Chasman2. 1. From the Division of Preventive Medicine (A.Y.C., F.G., S.M., P.M.R., D.I.C.), Division of Cardiovascular Medicine (S.M., P.M.R.), Division of Genetics (D.I.C.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Personalised Healthcare and Biomarkers AstraZeneca Research and Development, Alderley Park, United Kingdom (B.J.B.); Observational Research Center, AstraZeneca Research and Development, Mölndal (B.D., F.N.); and Unit of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (F.N.). aychu@partners.org. 2. From the Division of Preventive Medicine (A.Y.C., F.G., S.M., P.M.R., D.I.C.), Division of Cardiovascular Medicine (S.M., P.M.R.), Division of Genetics (D.I.C.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Personalised Healthcare and Biomarkers AstraZeneca Research and Development, Alderley Park, United Kingdom (B.J.B.); Observational Research Center, AstraZeneca Research and Development, Mölndal (B.D., F.N.); and Unit of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (F.N.).
Abstract
BACKGROUND: Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. METHODS AND RESULTS: One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for ≥ 1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. CONCLUSIONS: These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
RCT Entities:
BACKGROUND: Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. METHODS AND RESULTS: One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for ≥ 1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. CONCLUSIONS: These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
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