Genetic Inhibition of CETP, Ischemic Vascular Disease and Mortality, and Possible Adverse Effects
Open accessAbstract
Objectives This study tested whether genetic variation in the CETP gene is consistent with a protective effect of cholesteryl ester transfer protein (CETP) inhibition on risk of ischemic events and on total mortality, without the adverse effects reported for torcetrapib.Background Torcetrapib, an inhibitor of CETP, increased risk of death and ischemic cardiovascular disease of those randomized to the drug, despite improving the lipid profile.Methods The Copenhagen City Heart Study is a prospective cohort study of 10,261 individuals, aged 20 to 93 years, who were followed for up to 34 years (1976 to 2010). Of these, 2,087 developed ischemic heart disease, 1,064 developed ischemic cerebrovascular disease, and 3,807 died during follow-up. We selected 2 common genetic variants in CETP previously associated with reductions in CETP activity, thus mimicking the effect of pharmacological CETP inhibition.Results In individuals carrying 4 versus 0 high-density lipoprotein cholesterol-increasing alleles, there was an increase in levels of high-density lipoprotein cholesterol of up to 14% (0.2 mmol/l), and concomitant decreases in triglycerides, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol of, respectively, 6% (0.1 mmol/l), 3% (0.1 mmol/l), and 4% (0.2 mmol/l) (p for trend 0.004 to <0.001). Corresponding hazard ratios were 0.76 (95% confidence interval [CI]: 0.68 to 0.85) for any ischemic vascular event, 0.74 (95% CI: 0.65 to 0.85) for ischemic heart disease, 0.65 (95% CI: 0.54 to 0.79) for myocardial infarction, 0.77 (95% CI: 0.65 to 0.93) for ischemic cerebrovascular disease, 0.71 (95% CI: 0.58 to 0.88) for ischemic stroke, and 0.88 (95% CI: 0.80 to 0.97) for total mortality. CETP genotypes did not associate with variation in markers of possible side effects previously reported for torcetrapib.Conclusions Genetic CETP inhibition associates with reductions in risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, and ischemic stroke, with a corresponding antiatherogenic lipid profile, and with increased longevity, without adverse effects.
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Patients with genetically reduced CETP serum concentrations appear to have a slightly reduced risk of coronary heart disease.
“On the one hand, patients with genetically reduced CETP serum concentrations appear to have a slightly reduced risk of coronary heart disease [99–102].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [100]
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The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902 · see citing works
European guidelines on cardiovascular disease prevention in clinical practice: executive summary
Graham, I., Atar, D., Borch‐Johnsen, K., Boysen, G., Burell, G. K., Cífková, R., Dallongeville, J., Backer, G. D., Ebrahim, S. B. J., Gjelsvik, B., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm316 · Cited by 3,840 · see citing works
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487 · see citing works
Effects of torcetrapib in patients at high risk for coronary events
Barter, P. J., Caulfield, M., Eriksson, M., Grundy, S. M., Kastelein, J. J. P., Komajda, M., Lopez-Sendon, J., Mosca, L., Tardif, J.-C., Waters, D. D., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa0706628 · Cited by 3,139 · see citing works
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
The AIM-HIGH Investigators (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107579 · Cited by 2,911 · see citing works
Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058 · see citing works
Self-citationLarge-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
Cardiogenics, Schunkert, H., the CARDIoGRAM Consortium, König, I. R., Kathiresan, S., Reilly, M. P., Assimes, T. L., Holm, H., Preuss, M., Stewart, A. F. R., et al. (2011) · Nature Genetics · doi:10.1038/ng.784 · Cited by 1,866 · see citing works
Atherogenesis: a postprandial phenomenon.
Zilversmit, D. B. (1979) · Circulation · doi:10.1161/01.cir.60.3.473 · Cited by 1,701 · see citing works
Graham (2007) · doi:10.1097/01.hjr.0000277983.23934.c9 · Cited by 1,647 · see citing works
Grundy, S. M., Cleeman, J. I., Bairey Merz, C. N., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.07.001 · Cited by 1,550 · see citing works
Genetically Elevated Lipoprotein(a) and Increased Risk of Myocardial Infarction
Kamstrup, P. R. (2009) · JAMA · doi:10.1001/jama.2009.801 · Cited by 1,357 · see citing works
Chapman, M. J., Ginsberg, H. N., Amarenco, P., Andreotti, F., Borén, J., Catapano, A. L., Descamps, O. S., Fisher, E., Kovanen, P. T., Kuivenhoven, J. A., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr112 · Cited by 1,227 · see citing works
Self-citationInazu, A., Brown, M. L., Hesler, C. B., Agellon, L. B., Koizumi, J., Takata, K., Maruhama, Y., Mabuchi, H., & Tall, A. R. (1990) · New England Journal of Medicine · doi:10.1056/nejm199011013231803 · Cited by 862 · see citing works
Genetically elevated C-reactive protein and ischemic vascular disease
Zacho, J., Tybjærg-Hansen, A., Jensen, J. S., Grande, P., Sillesen, H., & Nordestgaard, B. G. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0707402 · Cited by 839 · see citing works
Self-citationSafety of anacetrapib in patients with or at high risk for coronary heart disease
Cannon, C. P., Shah, S., Dansky, H. M., Davidson, M., Brinton, E. A., Gotto, A. M., Stepanavage, M., Liu, S. X., Gibbons, P., Ashraf, T. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1009744 · Cited by 749 · see citing works
Nonfasting triglycerides and risk of ischemic stroke in the general population
Freiberg, J. J. (2008) · JAMA · doi:10.1001/jama.2008.621 · Cited by 542 · see citing works
Thompson, A. (2008) · JAMA · doi:10.1001/jama.299.23.2777 · Cited by 494 · see citing works
Brown, M. L., Inazu, A., Hesler, C. B., Agellon, L. B., Mann, C., Whitlock, M. E., Marcel, Y. L., Milne, R. W., Koizumi, J., Mabuchi, H., et al. (1989) · Nature · doi:10.1038/342448a0 · Cited by 467 · see citing works
Frikke-Schmidt, R. (2008) · JAMA · doi:10.1001/jama.299.21.2524 · Cited by 464 · see citing works
Self-citationNicholls, S. J., Brewer, H. B., Kastelein, J. J. P., Krueger, K. A., Wang, M.-D., Shao, M., Hu, B., McErlean, E., & Nissen, S. E. (2011) · JAMA · doi:10.1001/jama.2011.1649 · Cited by 410 · see citing works
Boekholdt, S. M., Sacks, F. M., Jukema, J. W., Shepherd, J., Freeman, D. J., McMahon, A. D., Cambien, F., Nicaud, V., de Grooth, G. J., Talmud, P. J., et al. (2005) · Circulation · doi:10.1161/01.cir.0000153341.46271.40 · Cited by 308 · see citing works
Tall, A. R., Yvan‐Charvet, L., & Wang, N. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000256728.60226.77 · Cited by 268 · see citing works
Langsted, A., Freiberg, J., Tybjærg‐Hansen, A., Schnohr, P., Jensen, G. B., & Nordestgaard, B. G. (2010) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02333.x · Cited by 230 · see citing works
Self-citationPolymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction
Ridker, P. M., Paré, G., Parker, A. N., Zee, R. Y. L., Miletich, J. P., & Chasman, D. I. (2009) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.108.817304 · Cited by 197 · see citing works
Schwartz, G. G., OLSSON, A. G., Ballantyne, C. M., Barter, P. J., Holme, I., Kallend, D. G., Leiter, L. A., Leitersdorf, E., McMurray, J. J. V., Shah, P. K., et al. (2009) · American Heart Journal · doi:10.1016/j.ahj.2009.09.017 · Cited by 182 · see citing works
Dachet, C., Poirier, O., Cambien, F., Chapman, J., & Rouis, M. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.2.507 · Cited by 168 · see citing works
Is raising HDL a futile strategy for atheroprotection?
JOY, T. R., & Hegele, R. A. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2489 · Cited by 135 · see citing works
CETP Inhibitors to Increase HDL Cholesterol Levels
Tall, A. R. (2007) · New England Journal of Medicine · doi:10.1056/nejme078029 · Cited by 128 · see citing works
Klerkx, A. H. E. M. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg013 · Cited by 123 · see citing works
Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population
Varbo, A., Nordestgaard, B. G., Tybjærg‐Hansen, A., Schnohr, P., Jensen, G. B., & Benn, M. (2011) · Annals of Neurology · doi:10.1002/ana.22384 · Cited by 122 · see citing works
Self-citationBorggreve, S. E., Hillege, H. L., Wolffenbuttel, B. H. R., de Jong, P. E., Zuurman, M. W., van der Steege, G., van Tol, A., & Dullaart, R. P. F. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2322 · Cited by 121 · see citing works
Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial
Stein, E. A., Roth, E. M., Rhyne, J. M., Burgess, T., Kallend, D. G., & Robinson, J. G. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehp601 · Cited by 109 · see citing works
Sofat, R., Hingorani, A. D., Smeeth, L., Humphries, S. E., Talmud, P. J., Cooper, J., Shah, T., Sandhu, M. S., Ricketts, S. L., Boekholdt, S. M., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.865444 · Cited by 104 · see citing works
van Venrooij, F. V., Stolk, R. P., Banga, J.-D., Sijmonsma, T., van Tol, A., Erkelens, D. W., Dallinga‐Thie, G. M., & for the DALI study group (2003) · Diabetes Care · doi:10.2337/diacare.26.4.1216 · Cited by 102 · see citing works
Polymorphisms in the CETP gene and association with CETP mass and HDL levels
Thompson, J. F., Lira, M. E., Durham, L. K., Clark, R. W., Bamberger, M. J., & Milos, P. M. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(03)00005-4 · Cited by 63 · see citing works
Corsetti, J. P., Ryan, D., Rainwater, D. L., Moss, A. J., Zaręba, W., & Sparks, C. E. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207977 · Cited by 47 · see citing works
McCaskie, P. A., Beilby, J. P., Chapman, C., Hung, J., McQuillan, B., Thompson, P. L., & Palmer, L. J. (2007) · Human Genetics · doi:10.1007/s00439-007-0326-2 · Cited by 38 · see citing works
Corella, D., Carrasco, P., Amiano, P., Arriola, L., Chirlaque, M. D., Huerta, J. M., Martínez, C., Martínez‐Camblor, P., Molina‐Montes, E., Navarro, C., et al. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.03.026 · Cited by 25 · see citing works
Niacin at 56 Years of Age — Time for an Early Retirement?
Giugliano, R. P. (2011) · New England Journal of Medicine · doi:10.1056/nejme1112346 · Cited by 22 · see citing works
High-Density Lipoprotein Cholesterol as the Holy Grail
Cannon, C. P. (2011) · JAMA · doi:10.1001/jama.2011.1687 · Cited by 21 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Frikke-Schmidt R, Nordestgaard BG, Stene MC, et al. Association of loss-of-function mutations in the ABCA1 gene with high-density Figure 4 Risk of Overall Mortality as a Function of Cholesteryl Ester Transfer Protein Genotype and Genotype Combination in the General Population Participants with ischemic heart disease and/or ischemic cerebrovascular dis- ease before entry were excluded. Hazard ratios were multifactorially adjusted for sex, age, body mass index, hypertension, diabetes mellitus, smoking, lipid- lowering therapy, alcohol consumption, physical inactivity, and, for women, post-menopausal status and hormone replacement therapy. The p values are tests for trend of hazard ratios with genotypes coded 0, 1, and 2, or 0, 1, 2, 3, and 4. 2047 JACC Vol. 60, No. 20, 2012
- Johannsen et al. November 13, 2012:2041-8 CETP and Ischemic Vascular Disease lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA 2008;299:2524 -32.
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Self-citationNordestgaard, B. G. (2016) · Circulation Research · doi:10.1161/circresaha.115.306249 · Cited by 1,116 · see citing works
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Madsen, C. M., Varbo, A., & Nordestgaard, B. G. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx163 · Cited by 715 · see citing works
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Self-citationTrials and Tribulations of CETP Inhibitors
Tall, A. R., & Rader, D. J. (2017) · Circulation Research · doi:10.1161/circresaha.117.311978 · Cited by 303 · see citing works
Ference, B. A., Kastelein, J. J. P., Ginsberg, H. N., Chapman, M. J., Nicholls, S. J., Ray, K. K., Packard, C. J., Laufs, U., Brook, R. D., Oliver-Williams, C., et al. (2017) · JAMA · doi:10.1001/jama.2017.11467 · Cited by 304 · see citing works
HDL cholesterol: reappraisal of its clinical relevance
März, W., Kleber, M. E., Scharnagl, H., Speer, T., Zewinger, S., Ritsch, A., Parhofer, K. G., von Eckardstein, A., Landmesser, U., & Laufs, U. (2017) · Clinical Research in Cardiology · doi:10.1007/s00392-017-1106-1 · Cited by 275 · see citing works
Hovingh, G. K., Kastelein, J. J. P., van Deventer, S. J. H., Round, P., Ford, J., Saleheen, D., Rader, D. J., Brewer, H. B., & Barter, P. J. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60158-1 · Cited by 237 · see citing works
Lipid-Lowering Agents: Targets Beyond PCSK9
Hegele, R. A., & Tsimikas, S. (2019) · Circulation Research · doi:10.1161/circresaha.118.313171 · Cited by 171 · see citing works
Burgess, S., Mason, A. M., Grant, A. J., Slob, E. A. W., Gkatzionis, A., Zuber, V., Patel, A. R., Tian, H., Liu, C., Haynes, W. G., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.12.017 · Cited by 148 · see citing works
HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology
Rosenson, R. S., Brewer, H. B., Barter, P. J., Björkegren, J., Chapman, M. J., Gaudet, D., Kim, D. S., Niesor, E. J., Rye, K., Sacks, F. M., et al. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.115 · Cited by 148 · see citing works
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Suresh, R., Li, X., Chiriac, A. E., Goel, K., Terzic, A., Pérez-Terzic, C. M., & Nelson, T. J. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.04.017 · Cited by 114 · see citing works
“In contrast, decreased expression of CETP as seen here in patients with recurrent events compared to the other two cohorts is associated with decreased risk of ischemic disease [29].”
ResultThe Role of Lipids and Lipoproteins in Atherosclerosis
Linton, M. F., Yancey, P. G., Davies, S. S., Jerome, W. G., Linton, E. F., Song, W., Doran, A. C., & Vickers, K. C. (2015) · Europe PMC (PubMed Central) · Cited by 108 · see citing works
New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B
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Cholesteryl ester transfer protein and its inhibitors
Shrestha, S., Wu, B. J., Guiney, L., Barter, P. J., & Rye, K. (2018) · Journal of Lipid Research · doi:10.1194/jlr.r082735 · Cited by 104 · see citing works
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BackgroundInfluentialHDL and cardiovascular disease
Nicholls, S. J., & Nelson, A. J. (2019) · Pathology · doi:10.1016/j.pathol.2018.10.017 · Cited by 100 · see citing works
Nurmohamed, N. S., Ditmarsch, M., & Kastelein, J. J. P. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab350 · Cited by 99 · see citing works
HDL and Reverse Remnant-Cholesterol Transport (RRT): Relevance to Cardiovascular Disease
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Management of residual risk after statin therapy
Reith, C. A., & Armitage, J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.12.018 · Cited by 91 · see citing works
KONES, R. J. (2013) · Vascular Health and Risk Management · doi:10.2147/vhrm.s37119 · Cited by 89 · see citing works
Madsen, C. M., Varbo, A., & Nordestgaard, B. G. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314050 · Cited by 87 · see citing works
Self-citationNomura, A., Won, H., Khera, A. V., Takeuchi, F., Ito, K., McCarthy, S., Emdin, C. A., Klarin, D. M., Natarajan, P., Zekavat, S. M., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311145 · Cited by 86 · see citing works
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BackgroundLauridsen, B. K., Stender, S., Frikke‐Schmidt, R., Nordestgaard, B. G., & Tybjærg‐Hansen, A. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv108 · Cited by 83 · see citing works
Self-citationMillwood, I. Y., Bennett, D., Holmes, M. V., Boxall, R., Guo, Y., Bian, Z., Yang, L., Sansome, S., Chen, Y., Du, H., et al. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2017.4177 · Cited by 83 · see citing works
Genetics of Lipid and Lipoprotein Disorders and Traits
Dron, J. S., & Hegele, R. A. (2016) · Current Genetic Medicine Reports · doi:10.1007/s40142-016-0097-y · Cited by 76 · see citing works
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“terol) was associated with reduced mortality [129].”
BackgroundSelf-citationNelson, A. J., Sniderman, A. D., Ditmarsch, M., Dicklin, M. R., Nicholls, S. J., Davidson, M. H., & Kastelein, J. J. P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169417 · Cited by 71 · see citing works
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Lacey, B., Herrington, W. G., Preiss, D., Lewington, S., & Armitage, J. (2017) · Current Atherosclerosis Reports · doi:10.1007/s11883-017-0661-2 · Cited by 66 · see citing works
Kjeldsen, E. W., Thomassen, J. Q., & Frikke‐Schmidt, R. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.159063 · Cited by 67 · see citing works
Self-citationHomozygous autosomal dominant hypercholesterolaemia
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Nordestgaard, L. T., Christoffersen, M., Lauridsen, B. K., Afzal, S., Nordestgaard, B. G., Frikke‐Schmidt, R., & Tybjærg‐Hansen, A. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2021.3728 · Cited by 62 · see citing works
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Future of Cholesteryl Ester Transfer Protein Inhibitors
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“(56), the CETP SNPs IVS1+279 G > A (TaqIB) and −629 C > A, both associated with reduction in CETP activity, were confirmed to be associated with both increased HDL-C and reduced LDL-C and were found to be significantly associated with reduced risk of incident ischemic vascular events.”
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New Era of Lipid-Lowering Drugs
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BackgroundMethodInfluentialCETP (Cholesteryl Ester Transfer Protein) Concentration
Blauw, L. L., Li‐Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbée, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., et al. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.117.002034 · Cited by 54 · see citing works
Plasma high density lipoproteins: Therapeutic targeting and links to atherogenic inflammation
Tall, A. R. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.07.004 · Cited by 54 · see citing works
High-Density Lipoprotein Cholesterol and All-Cause and Cause-Specific Mortality Among the Elderly
Li, Z., Lv, Y., Zhong, W.-F., Gao, X., Kraus, V. B., Zou, M., Zhang, X.-R., Li, F.-R., Yuan, J.-Q., Shi, X., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-02511 · Cited by 54 · see citing works
Furtado, J. D., Ruotolo, G., Nicholls, S. J., Dullea, R., Carvajal‐Gonzalez, S., & Sacks, F. M. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.317181 · Cited by 53 · see citing works
Human genetics of HDL: Insight into particle metabolism and function
Brunham, L. R., & Hayden, M. R. (2015) · Progress in Lipid Research · doi:10.1016/j.plipres.2015.01.001 · Cited by 52 · see citing works
High-density lipoproteins (HDL): Novel function and therapeutic applications
Darabi, M., & Kontush, A. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.159058 · Cited by 52 · see citing works
Mendelian Disorders of High-Density Lipoprotein Metabolism
Oldoni, F., Sinke, R. J., & Kuivenhoven, J. A. (2014) · Circulation Research · doi:10.1161/circresaha.113.300634 · Cited by 48 · see citing works
“Despite the presence of frequent CETP variants with significant effects on HDL-C, the role of CETP in atherogenesis remains controversial.(52,53,189) In mice, which naturally lack CETP, the introduction of the human CETP transgene decreases HDL-C and apoA-I levels,(190) whereas overexpression can either increase or de…”
BackgroundHovingh, G. K., Rader, D. J., & Hegele, R. A. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000161 · Cited by 48 · see citing works
“[35] showed that variants in the CETP gene that reduced CETP levels were associated with higher HDL-C, lower LDL-C and triglycerides plasma levels.”
BackgroundPharmacotherapies for lipid modification: beyond the statins
Gotto, A. M., & Moon, J. E. (2013) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2013.117 · Cited by 44 · see citing works
Poliakova, T., & Wellington, C. L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00671-y · Cited by 42 · see citing works
“…expression [127] and increased HDL [170] Decreased CAD risk [171] No association [172] rs1800775(-629C > A) Decreased [132] Mixed:Increased MI risk [131] Higher CAD risk [173] Reduced IHD, MI, ICVD, and IS risks [174] Mixed: No association [175] Decreased in an APOE ε4 allele-dependent fashion.”
BackgroundA Novel Role for CETP as Immunological Gatekeeper: Raising HDL to Cure Sepsis?
Blauw, L. L., Wang, Y., van Dijk, K. W., & Rensen, P. C. N. (2020) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.01.003 · Cited by 40 · see citing works
HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome
Alcover, S., Ramos-Regalado, L., Girón, G., Muñoz‐García, N., & Vilahur, G. (2025) · Antioxidants · doi:10.3390/antiox14040434 · Cited by 45 · see citing works
“Likewise, genetic modifications that reduce CETP activity are associated with a decreased risk of CVD [117], resulting in increased HDL-C levels and reduced LDL-C levels.”
Ooi, E. M. M., Barrett, P. H. R., & Watts, G. F. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.06.069 · Cited by 38 · see citing works
Cholesteryl Ester Transfer Protein Inhibition Is Not Yet Dead—Pro
Barter, P. J., & Rye, K. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.115.306879 · Cited by 36 · see citing works
“People with these polymorphisms also lived longer, with no evidence of adverse effects.(4)”
BackgroundObicetrapib—the Rebirth of CETP Inhibitors?
Chang, B. J., Laffin, L. J., Sarraju, A., & Nissen, S. E. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01231-5 · Cited by 36 · see citing works
“Several subsequent human studies including the Copenhagen City Heart Study, demonstrated that two common CETP reduced-function polymorphisms were associated with reduced MACE and mortality [17].”
BackgroundNovel Therapies Focused on the High-Density Lipoprotein Particle
van Capelleveen, J. C., Brewer, H. B., Kastelein, J. J. P., & Hovingh, G. K. (2014) · Circulation Research · doi:10.1161/circresaha.114.301804 · Cited by 34 · see citing works
Targeting High-density Lipoproteins to Reduce Cardiovascular Risk: What Is the Evidence?
Barter, P. J., & Rye, K. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.07.021 · Cited by 34 · see citing works
Cholesteryl ester transfer protein inhibitors: challenges and perspectives
Filippatos, T. D., Klouras, E., Barkas, F., & Elisaf, M. (2016) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2016.1189327 · Cited by 33 · see citing works
“Importantly, no association was found between CETP genotypes and markers of possible side effects [29].”
BackgroundAssociation of genetically predicted lipid traits and lipid-modifying targets with heart failure
Xiao, J., Ji, J., Zhang, N., Yang, X., Chen, K., Chen, L., & Huang, W. (2022) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwac290 · Cited by 31 · see citing works
Emerging Risk Factors for Stroke
Hopewell, J. C., & Clarke, R. (2016) · Stroke · doi:10.1161/strokeaha.115.010646 · Cited by 31 · see citing works
“For example, genetic variants in the CETP gene that lower cholesterylester transfer protein (CETP) activity (and influence various lipid fractions) and thus mimic the effect of CETP inhibition have been associated with lower risk of IS (and CHD), suggesting that this pathway of lipid modification may be beneficial.(16…”
BackgroundZein, M. A., Khazzeka, A., Khoury, A. E., Zein, J. A., Dima, Z., & Eid, A. H. (2024) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2024.10.009 · Cited by 32 · see citing works
Causal Effect of Lipids and Lipoproteins on Atherosclerosis
Ference, B. A. (2018) · Cardiology Clinics · doi:10.1016/j.ccl.2017.12.001 · Cited by 28 · see citing works
Barter, P. J., Nicholls, S. J., Kastelein, J. J. P., & Rye, K.-A. (2015) · Circulation · doi:10.1161/circulationaha.114.014025 · Cited by 29 · see citing works
“Furthermore, the larger the number of affected alleles, the greater the effect on ASCVD risk.(45) People with these polymorphisms also had increased longevity, with no evidence of adverse effects.”
BackgroundGenetics of HDL-C: A Causal Link to Atherosclerosis?
van Capelleveen, J. C., Bochem, A. E., Motazacker, M. M., Hovingh, G. K., & Kastelein, J. J. P. (2013) · Current Atherosclerosis Reports · doi:10.1007/s11883-013-0326-8 · Cited by 28 · see citing works
CETP‐Inhibition and HDL‐Cholesterol: A Story of CV Risk or CV Benefit, or Both
Nicholls, S. J. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1118 · Cited by 25 · see citing works
Low High-Density Lipoprotein Cholesterol and High White Blood Cell Counts
Harsløf, M., Pedersen, K. M., Nordestgaard, B. G., & Afzal, S. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314983 · Cited by 25 · see citing works
Self-citationBonfiglio, C., Leone, C. M., Silveira, L. V. D. A., Guerra, R., Misciagna, G., Caruso, M. G., Bruno, I., Buongiorno, C., Campanella, A., Guerra, V. M. B., et al. (2020) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2020.07.002 · Cited by 24 · see citing works
Frikke‐Schmidt, R. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.03.005 · Cited by 23 · see citing works
Self-citationLipid-lowering efficacy of obicetrapib: A comprehensive systematic review and meta-analysis
Masson, W., Barbagelata, L., Lobo, M., Nogueira, J. P., & Handelsman, Y. (2025) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2024.12.016 · Cited by 23 · see citing works
Dixit, S. M., Ahsan, M., & Senapati, S. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00301 · Cited by 22 · see citing works
Kathiresan, S. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.967 · Cited by 21 · see citing works
“(5) use naturally occurring human genetic variation to address these research questions.”
BackgroundThe mystery of evacetrapib - why are CETP inhibitors failing?
Nicholls, S. J., & Bubb, K. J. (2020) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2020.1745633 · Cited by 21 · see citing works
“tinues to present a potential cardioprotective strategy [3,4,35].”
BackgroundBell, T. A., Graham, M. J., Lee, R. G., Mullick, A. E., Fu, W., Norris, D., & Crooke, R. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m036509 · Cited by 20 · see citing works
“These results were validated by recent findings from the Copenhagen City Heart Study, where genetic inhibition of CETP was associated with increased in HDL-C and reduction in plasma TG, LDL-C, non-HDL-C, and adverse events (47).”
Wu, B. J., Shrestha, S., Ong, K. L., Johns, D. G., Hou, L., Barter, P. J., & Rye, K. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304747 · Cited by 19 · see citing works
Cholesteryl Ester Transfer Protein Inhibitors
McLain, J. H., Alsterda, A. J., & Arora, R. R. (2016) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248416662349 · Cited by 19 · see citing works
“The strongest genetics argument for the antiatherogenic effects of CETP deficiency came from the Copenhagen City Heart Study in which 10 261 patients were followed for over 34 years.(35) They looked at the occurrence of 2 common CETP variants associated with decreased CETP activity (rs1800775, rs708272) and compared t…”
BackgroundCan we revive CETP-inhibitors for the prevention of cardiovascular disease?
Nicholls, S. J., Ray, K. K., Nelson, A. J., & Kastelein, J. J. P. (2022) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000854 · Cited by 19 · see citing works
CETP Inhibitors: Should We Continue to Pursue This Pathway?
Nicholls, S. J., & Nelson, A. J. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01070-2 · Cited by 19 · see citing works
Yu, C., Bakshi, A., Watts, G. F., Renton, A. E., Fulton‐Howard, B., Goate, A., Natarajan, P., Chasman, D. I., Robman, L. D., Woods, R. L., et al. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.031459 · Cited by 19 · see citing works
“34,38 43 In addition, a recent Danish study suggested that genetic CETP deficiency, mimicking pharmacologic CETP inhibition, was associated with lower ASCVD risk but with an increased risk of AMD.”
BackgroundClinical trials with cholesteryl ester transfer protein inhibitors
Bartolo, B. A. D., Duong, M., & Nicholls, S. J. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000352 · Cited by 18 · see citing works
“This is supported by genetic studies demonstrating that polymorphisms resulting in low CETP activity also associate with high HDL-C levels and low cardiovascular risk [6,11,12].”
BackgroundLorkowski, S. W., & Smith, J. D. (2022) · Biomedicines · doi:10.3390/biomedicines10010128 · Cited by 17 · see citing works
“In contrast, two common SNPs leading to reductions in CETP activity and increased HDL-C levels are also associated with decreased risk of CHD [31], thus supporting the HDL hypothesis.”
ResultCETP inhibition, statins and diabetes
Barter, P. J., Cochran, B. J., & Rye, K. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.09.033 · Cited by 17 · see citing works
CETP Inhibition in CVD Prevention: an Actual Appraisal
Bartolo, B. A. D., Takata, K., Duong, M., & Nicholls, S. J. (2016) · Current Cardiology Reports · doi:10.1007/s11886-016-0724-y · Cited by 16 · see citing works
Statin Combination Therapy and Cardiovascular Risk Reduction
Toth, P. P., Farnier, M., Tomassini, J. E., Foody, J. M., & Tershakovec, A. M. (2016) · Future Cardiology · doi:10.2217/fca-2015-0011 · Cited by 16 · see citing works
Allard‐Ratick, M., Sandesara, P. B., Quyyumi, A. A., & Sperling, L. S. (2019) · US Cardiology Review · doi:10.15420/usc.2019.3.2 · Cited by 13 · see citing works
Journey Through Cholesteryl Ester Transfer Protein Inhibition
Karalis, I. K., Rensen, P. C. N., & Jukema, J. W. (2013) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.111.000014 · Cited by 12 · see citing works
“Quite confusingly, the Copenhagen City Heart Study initially demonstrated an increased risk for CAD, despite higher serum HDL-C in women with a lossof-function CETP polymorphism, and a 36% lower risk for CAD in women with low HDL-C in the context of gainof-function mutations,(20) findings that were questioned by a mor…”
ResultPovsic, T. J., Scott, R. C., Mahaffey, K. W., Blaustein, R. O., Edelberg, J. M., Lefkowitz, M. P., Solomon, S. D., Fox, J. C., Healy, K. E., Khakoo, A. Y., et al. (2017) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-017-6739-9 · Cited by 12 · see citing works
Christen, T., Trompet, S., Noordam, R., Blauw, L. L., Gast, K. B., Rensen, P. C. N., van Dijk, K. W., Rosendaal, F. R., de Mutsert, R., & Jukema, J. W. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.10.023 · Cited by 12 · see citing works
Cholesteryl Ester Transfer Protein Inhibitors as Agents to Reduce Coronary Heart Disease Risk
Barter, P. J., & Rye, K. (2018) · Cardiology Clinics · doi:10.1016/j.ccl.2017.12.011 · Cited by 12 · see citing works
Using human genetics to predict the effects and side-effects of drugs
Stender, S., & Tybjærg‐Hansen, A. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000280 · Cited by 12 · see citing works
Self-citationDabravolski, S. A., Orekhov, N. A., Melnichenko, A. А., Sukhorukov, V. N., Popov, M. A., & Orekhov, A. N. (2024) · Current Pharmaceutical Design · doi:10.2174/0113816128284695240219093612 · Cited by 12 · see citing works
Obicetrapib and its impact on lipid parameters: A comprehensive meta-analysis of the latest evidence
Bhatti, M. I., Safiullah, M., Farhan, K., Ali, A., Abdullah, S., Ali, A., & Ahmed, R. (2025) · Journal of clinical lipidology · doi:10.1016/j.jacl.2025.07.003 · Cited by 11 · see citing works
HDL as a Causal Factor in Atherosclerosis: Insights from Human Genetics
Brunham, L. R. (2016) · Current Atherosclerosis Reports · doi:10.1007/s11883-016-0623-0 · Cited by 13 · see citing works
Looking into the Crystal Ball—Upcoming Drugs for Dyslipidemia
George, M., Selvarajan, S., Rajaram, M., & Shanmugam, E. (2014) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248414545127 · Cited by 11 · see citing works
“Further the study reported a favorable antiatherogenic lipid profile with increased longevity in such patients.(11) The growing evidence on the association between CETP and HDL have led to the discovery and development of newer molecules to raise HDL level through CETP inhibition.”
BackgroundLauridsen, B. K., Stender, S., Frikke‐Schmidt, R., Nordestgaard, B. G., & Tybjærg‐Hansen, A. (2017) · International Journal of Epidemiology · doi:10.1093/ije/dyx096 · Cited by 11 · see citing works
Self-citationKlinische Bedeutung des HDL-Cholesterins
März, W., Kleber, M. E., Scharnagl, H., Speer, T., Zewinger, S., Ritsch, A., Parhofer, K. G., von Eckardstein, A., Landmesser, U., & Laufs, U. (2016) · Herz · doi:10.1007/s00059-016-4499-0 · Cited by 11 · see citing works
LDL, HDL, VLDL, and CVD Prevention: Lessons from Genetics?
Hewing, B., & Landmesser, U. (2015) · Current Cardiology Reports · doi:10.1007/s11886-015-0610-z · Cited by 11 · see citing works
The potential of cholesteryl ester transfer protein as a therapeutic target
Gautier, T., Masson, D., & Lagrost, L. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2015.1073713 · Cited by 10 · see citing works
“Similarly, genetic studies reported that variation at the CETP gene associated with moderate decrease in plasma CETP activity and increase in HDL to LDL cholesterol ratio could be protective, but these data do not allow to predict whether more pronounced changes in CETP activity and HDL cholesterol concentration (such…”
BackgroundMonogenic causes of elevated HDL cholesterol and implications for development of new therapeutics
Larach, D. B., Cuchel, M., & Rader, D. J. (2013) · Clinical Lipidology · doi:10.2217/clp.13.73 · Cited by 10 · see citing works
Antisense Oligonucleotides, microRNAs, and Antibodies
Dávalos, A., & Chroni, A. (2014) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-09665-0_22 · Cited by 10 · see citing works
“This finding together with a previous study regarding the lack of association of genetic inhibition of CETP (Johannsen et al. 2012) and possible side effects previously reported for torcetrapib suggests that not all inhibitors of CETP are equal.”
ResultKoopal, C., van der Graaf, Y., Asselbergs, F. W., Westerink, J., & Visseren, F. L. J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.08.015 · Cited by 10 · see citing works
- Authors
- Johannsen, T. H., Frikke-Schmidt, R., Schou, J., Nordestgaard, B. G., & Tybjærg-Hansen, A.
- Affiliations
- University of Copenhagen (DK)
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 60
- Issue
- 20
- Pages
- 2041-2048
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2030157055
- Cited by
- 156
- References
- 41
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 11 · 2018: 12 · 2017: 16 · 2016: 18 · 2015: 18 · 2014: 12 · 2013: 12 · 2012: 1
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- European Union, Sixth Framework Programme Priority (FP-2005-LIFESCIHEALTH-6)
- Ingeborg and Leo Dannin's Grant
- Henry Hansen's and Wife's Grant
- Odd Fellow Order
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- P, cholesteryl ester transfer protein, CETP gene polymorphisms, torcetrapib, ischemic heart disease, ischemic cerebrovascular disease, ischemic stroke, myocardial infarction, all-cause mortality, HDL cholesterol, triglycerides, LDL cholesterol, non-HDL cholesterol, ischemic vascular disease
- MeSH terms
- Adult, Aged, Aged, 80 and over, Anticholesteremic Agents, Cardiovascular Diseases, Female, Genotype, Humans, Male, Middle Aged, Quinolines, Risk Factors, Genetic Variation, Cohort Studies, Myocardial Ischemia, Cholesterol Ester Transfer Proteins, Young Adult
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