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Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease
Open accessAbstract
BACKGROUND: A low plasma level of low-density lipoprotein (LDL) cholesterol is associated with reduced risk of coronary heart disease (CHD), but the effect of lifelong reductions in plasma LDL cholesterol is not known. We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population. METHODS: We compared the incidence of CHD (myocardial infarction, fatal CHD, or coronary revascularization) over a 15-year interval in the Atherosclerosis Risk in Communities study according to the presence or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol. RESULTS: Of the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9; these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD (P=0.008 for the reduction; hazard ratio, 0.11; 95 percent confidence interval, 0.02 to 0.81; P=0.03). Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD (hazard ratio, 0.50; 95 percent confidence interval, 0.32 to 0.79; P=0.003). CONCLUSIONS: These data indicate that moderate lifelong reduction in the plasma level of LDL cholesterol is associated with a substantial reduction in the incidence of coronary events, even in populations with a high prevalence of non-lipid-related cardiovascular risk factors.
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In the citing paper
“Proprotein convertase subtilisin-kexin type 9 (PCSK9) promotes degradation of LDL receptors, thereby diminishing the clearance of LDL from the circulation. 6”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In 2005, a causative association was established between the presence of loss-of-function mutations in PCSK9 and lifelong reductions in LDL-C associated with lower CHD risk (3).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Genetic studies have shown that carriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction.7,8”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These data suggest that drugs that ultimately reduce LDL-C level predominantly through upregulation of LDL receptor expression should, barring any off-target adverse effects, lead to clinical benefit in proportion to the degree of LDL-C reduction.64”
From Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis (2016) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Some of the most important human metabolic disease genes have been identified using germline genetic methods such as GWAS and whole exome sequencing42-44.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [44]
Experimental — accuracy not yet measured
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In the citing paper
“Unlike gain-of-function PCSK9 variants (7), loss-of-function (LOF) variants enhance LDLR levels and promote LDLc clearance (4, 8).”
From Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR cleaved by furin (2021) · cites this paper as [8]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“mutations conveying gain or loss of function of PCSK9 result in a higher or lower level of LDL cholesterol, respectively, which in turn is associated with a corresponding higher 7 or lower 6 risk of incident coronary heart disease.”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Whereas PCSK9 loss-of-function mutations carriers with lifelong reductions in LDL-C and coronary heart disease incidence, were not initially found at significantly reduced risk of stroke (3, 72), a much larger study of the UK Biobank database described the first genetic evidence of a protective effect of the R46L loss-of-function mutation on PCSK9 on ischemic stroke (73).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [3]
In the citing paper
“and that lowering LDL-C reduces the risk of ASCVD proportionally to the absolute achieved reduction in LDL-C [2,51].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [51]
In the citing paper
“The remarkable consistency among these studies, in addition to biological and experimental evidence, provides compelling evidence that LDL-C is causally associated with the risk of ASCVD”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [51]
In the citing paper
“Both studies had relatively short follow-up periods and the evidence from statin trials indicates that the clinical benefits of LDL-lowering may only emerge after about 1 year [51], so these trials may have underestimated the potential impact of longer-term treatment [120,290].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [51]
In the citing paper
“These developments have enabled researchers to bridge the gap between the monogenic and polygenic realms, identifying common variant modifiers of monogenic phenotypes contributing to the variable expression of rare, large-effect alleles26,93, and low-frequency and rare variants that influence common multifactorial traits94,95.”
From A brief history of human disease genetics (2020) · cites this paper as [95]
In the citing paper
“At the same time, it has become increasingly evident now that not only the magnitude of LDL-C lowering is important but that the duration of exposure to elevated LDL-C levels is equally important [11,16,38].”
In the citing paper
“Additionally, increasing evidence also suggests that the duration of exposure to low LDL-C levels may be as important as the magnitude of LDL-C lowering [11][12][13][14][15][16].”
In the citing paper
“The exceptionally low rates of CV events observed in patients carrying mutations in PCSK9 or other similar genes despite only modestly low LDL-C levels strongly support this notion [11].”
In the citing paper
“Hobbs and Cohen sequenced the gene (126, 127) and identified low-frequency common variants (0.5 to 1%), which allowed epidemiological research documenting a protective effect on myocardial infarction (128).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [128]
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Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198
THE ATHEROSCLEROSIS RISK IN COMMUNIT (ARIC) STUDY: DESIGN AND OBJECTIVES
THE ARIC INVESTIGATORS (1989) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a115184 · Cited by 3,510
(1989) · PubMed · Cited by 3,139
Law, M. R., Wald, N. J., & Rudnicka, A. R. (2003) · BMJ · doi:10.1136/bmj.326.7404.1423 · Cited by 1,720
Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., & Hobbs, H. H. (2005) · Nature Genetics · doi:10.1038/ng1509 · Cited by 1,381
Self-citationSeidah, N. G., Benjannet, S., Wickham, L., Marcinkiewicz, J., Jasmin, S. B., Stifani, S., Basak, A., Prat, A., & Chrétien, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0335507100 · Cited by 1,191
CORONARY DISEASE AMONG UNITED STATES SOLDIERS KILLED IN ACTION IN KOREA
Enos, W. F. (1953) · JAMA · doi:10.1001/jama.1953.03690120006002 · Cited by 891
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Saavedra, Y. G. L., Dufour, R., & Baass, A. W. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.08.005 · Cited by 54
An Evolutionary Framework for Association Testing in Resequencing Studies
King, C. R., Rathouz, P. J., & Nicolae, D. L. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001202 · Cited by 54
Si‐Tayeb, K., Idriss, S., Champon, B., Caillaud, A., Pichelin, M., Arnaud, L., Lemarchand, P., May, C. L., Zibara, K., & Cariou, B. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.022277 · Cited by 54
Ohta, N., Hori, M., Takahashi, A., Ogura, M., Makino, H., Tamanaha, T., Fujiyama, H., Miyamoto, Y., & Harada‐Shiba, M. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.12.024 · Cited by 54
Diogo, D., Okada, Y., & Plenge, R. M. (2013) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000012 · Cited by 54
Discovery of rare variants for complex phenotypes
Kosmicki, J. A., Churchhouse, C. L., Rivas, M. A., & Neale, B. M. (2016) · Human Genetics · doi:10.1007/s00439-016-1679-1 · Cited by 54
The role of registries and genetic databases in familial hypercholesterolemia
Kindt, I., Mata, P., & Knowles, J. W. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000398 · Cited by 54
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Evison, B. J., Palmer, J. T., Lambert, G. C., Treutlein, H., Zeng, J., Nativel, B., Chemello, K., Zhu, Q. X., Wang, J., Teng, Y., et al. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115344 · Cited by 54
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Dong, J., He, M., Li, J., Pessentheiner, A., Wang, C., Zhang, J., Sun, Y., Wang, W.-T., Zhang, Y., Liu, J., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.143812 · Cited by 53
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Dixon, D. L., Trankle, C., Buckley, L., Parod, E., Carbone, S., Van Tassell, B. W., & Abbate, A. (2016) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2016.07.004 · Cited by 53
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Porto, E. M., & Komor, A. C. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002071 · Cited by 53
The PCSK9 revolution and the potential of PCSK9-based therapies to reduce LDL-cholesterol
Seidah, N. G. (2017) · Global Cardiology Science and Practice · doi:10.21542/gcsp.2017.2 · Cited by 53
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Kannt, A., & Wieland, T. (2016) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-016-1216-8 · Cited by 53
Brouwers, M. C. G. J., Simons, N., Stehouwer, C. D. A., Koek, G. H., Schaper, N. C., & Isaacs, A. J. (2019) · Hepatology Communications · doi:10.1002/hep4.1319 · Cited by 53
Ntzani, E., Rizos, E. C., & Ioannidis, J. P. A. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwk085 · Cited by 53
Yang, H., Ratnapriya, R., Cogliati, T., Kim, J.-W., & Swaroop, A. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.01.005 · Cited by 52
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Safarova, M. S., Bimal, T., Soffer, D. E., Hirsh, B. J., Shapiro, M. D., Mintz, G. L., Cha, A., & Gianos, E. (2024) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2024.100701 · Cited by 52
Burger, P. M., Dorresteijn, J. A. N., Koudstaal, S., Holtrop, J., Kastelein, J. J. P., Jukema, J. W., Ridker, P. M., Mosterd, A., & Visseren, F. L. J. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.118540 · Cited by 52
Dávalos, A., & Fernandez-Hernando, C. F. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.02.005 · Cited by 52
PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models of hypertension
Berger, J.-M., Vaillant, N., May, C. L., Calderon, C., Brégeon, J., Prieur, X., Hadchouel, J., Loirand, G., & Cariou, B. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.012 · Cited by 52
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Norris, J. M., & Rich, S. S. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.255463 · Cited by 52
Aung, L. H. H., Yin, R., Miao, L., Hu, X.-J., Yan, T.-T., Cao, X., Wu, D., Li, Q., Pan, S., & Wu, J. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-5 · Cited by 52
Li, J., Li, S., Zhang, Y., Xu, R., Guo, Y., Zhu, C., Wu, N., Qing, P., Gao, Y., Sun, J., et al. (2015) · Medicine · doi:10.1097/md.0000000000002426 · Cited by 52
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Greene, C. S., & Voight, B. F. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw160 · Cited by 52
Inflammation and beyond: new directions and emerging drugs for treating atherosclerosis
Bertrand, M.-J., & Tardif, J. (2016) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2017.1269743 · Cited by 52
Leshchiner, E. S., Rush, J. S., Durney, M. A., Cao, Z., Dančík, V., Chittick, B., Wu, H., Petrone, A., Bittker, J. A., Phillips, A. J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705748114 · Cited by 52
Therapeutic Genome Editing in Cardiovascular Diseases
German, D. M., Mitalipov, S. M., Mishra, A., & Kaul, S. (2019) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2018.11.004 · Cited by 52
In vivo PCSK9 gene editing using an all-in-one self-cleavage AAV-CRISPR system
Li, Q., Su, J., Liu, Y., Jin, X., Zhong, X., Mo, L., Wang, Q., Deng, H., & Yang, Y. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.005 · Cited by 52
Kim, Y., Landstrom, A. P., Shah, S. H., Wu, J. C., & Seidman, C. E. (2024) · Circulation · doi:10.1161/cir.0000000000001296 · Cited by 51
Hallman, D. M., Srinivasan, S. R., Chen, W., Boerwinkle, E., & Berenson, G. S. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.02.057 · Cited by 51
Self-citationPCSK9 gene mutations and low-density lipoprotein cholesterol
Wu, N., & Li, J. (2014) · Clinica Chimica Acta · doi:10.1016/j.cca.2014.01.043 · Cited by 51
PCSK9 regulates the chemokine receptor CCR2 on monocytes
Grune, J., Meýborg, H., Bezhaeva, T., Kappert, K., Hillmeister, P., Kintscher, U., Pieske, B. M., & Stawowy, P. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.02.085 · Cited by 51
Wang, H., Wang, Q., Wang, J., Guo, C., Kleiman, K., Meng, H., Knight, J. S., & Eitzman, D. T. (2017) · Scientific Reports · doi:10.1038/s41598-017-14307-x · Cited by 51
Robinson, J. R., Denny, J. C., Roden, D. M., & Driest, S. L. V. (2017) · Clinical and Translational Science · doi:10.1111/cts.12522 · Cited by 51
Characterization of the role of EGF-A of low density lipoprotein receptor in PCSK9 binding
Gu, H.-M., Adijiang, A., Mah, M., & Zhang, D. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m041129 · Cited by 51
Diabetes alters LDL receptor and PCSK9 expression in rat liver
Niesen, M. I., Bedi, M., & Lopez, D. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.11.009 · Cited by 51
Genetics: A gene of rare effect
Hall, S. S. (2013) · Nature · doi:10.1038/496152a · Cited by 51
Low LDL cholesterol by PCSK9 variation reduces cardiovascular mortality
Benn, M., Tybjærg-Hansen, A., & Nordestgaard, B. G. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.03.517 · Cited by 51
Update on the laboratory investigation of dyslipidemias
Ramasamy, I. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.01.015 · Cited by 50
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PCSK9: an emerging target for treatment of hypercholesterolemia
Duff, C. J., & Hooper, N. M. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.547480 · Cited by 50
Dyslipidemia management update
Chang, Y., & Robidoux, J. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.04.005 · Cited by 50
Genome editing in large animal models
Maynard, L. H., Humbert, O., Peterson, C. W., & Kiem, H. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.026 · Cited by 50
Next Steps in Primary Prevention of Coronary Heart Disease
DOMANSKI, M. J., Fuster, V., Díaz‐Mitoma, F., Grundy, S. M., Lloyd‐Jones, D. M., Mamdani, M., Roberts, R. E., Thorpe, K. E., Hall, J., Udell, J. A., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.08.857 · Cited by 50
Silencing human genetic diseases with oligonucleotide-based therapies
Martı́nez, T., Wright, N., López‐Fraga, M., Jiménez, A. I., & Pañeda, C. (2013) · Human Genetics · doi:10.1007/s00439-013-1288-1 · Cited by 50
PCSK9 inhibitors in the prevention of cardiovascular disease
Latimer, J., Batty, J. A., Neely, R. D. G., & Kunadian, V. (2016) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-016-1364-1 · Cited by 50
Kohli, P., Ganz, P., Ma, Y., Scherzer, R., Hur, S., Weigel, B., Grünfeld, C., Deeks, S. G., Wasserman, S. M., Scott, R. C., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.002683 · Cited by 50
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Quispe, R., Hendrani, A. D., Elshazly, M. B., Michos, E. D., McEvoy, J. W., Blaha, M. J., Banach, M., Kulkarni, K. R., Toth, P. P., Coresh, J., et al. (2017) · BMC Medicine · doi:10.1186/s12916-017-0852-2 · Cited by 50
Guo, S., Lu, J., Zhuo, Y., Xiao, M., Xue, X., Zhong, S., Shen, X., Yin, C., Li, L., Chen, Q., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.101069 · Cited by 50
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Rannikko, J., Sanz, D. J., Ortutay, Z., Seiskari, T., Aittoniemi, J., Huttunen, R., Syrjänen, J., & Pesu, M. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12946 · Cited by 50
Caselli, C., Turco, S. D., Ragusa, R., Lorenzoni, V., Graaf, M. A. D., Basta, G., Scholte, A. J. H. A., Caterina, R. D., & Neglia, D. (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0949-3 · Cited by 50
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Ajoolabady, A., Pratico, D., Mazidi, M., Davies, I. G., Lip, G. Y. H., Seidah, N., Libby, P., Kroemer, G., & Ren, J. (2025) · Metabolism · doi:10.1016/j.metabol.2024.156064 · Cited by 49
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Kamb, A., Harper, S., & Stefánsson, K. (2013) · Nature Biotechnology · doi:10.1038/nbt.2732 · Cited by 49
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Marais, D. A., Blom, D. J., Petrides, F., Gouëffic, Y., & Lambert, G. C. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283587563 · Cited by 49
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Vogt, A. (2015) · The Application of Clinical Genetics · doi:10.2147/tacg.s44315 · Cited by 49
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Abifadel, M., Bernier, L., Dubuc, G., Nuel, G., Rabès, J., Bonneau, J., Marques, A. P., Marduel, M., Devillers, M., Münnich, A., et al. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.059980 · Cited by 49
Li, H., & Liu, J. (2012) · Biochemical Journal · doi:10.1042/bj20111645 · Cited by 49
Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9
Ason, B. L., Tep, S., Davis, J. H. R., Xu, Y., Tetzloff, G. G., Galinski, B., Soriano, F., Dubinina, N., Zhu, L., Stefanni, A. C., et al. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m013664 · Cited by 49
Roth, E. M., & Diller, P. M. (2014) · Future Cardiology · doi:10.2217/fca.13.107 · Cited by 49
Niiranen, T., & Vasan, R. S. (2016) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2016.1176528 · Cited by 49
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Hamsten, A., & Eriksson, P. O. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.01958.x · Cited by 49
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Baldini, F., Portincasa, P., Grasselli, E., Damonte, G., Salis, A., Bonomo, M., Florio, M., Serale, N., Voci, A., Gena, P., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2019.158586 · Cited by 48
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Ferguson, J. F., Matthews, G. J., Townsend, R. R., Raj, D. S., Kanetsky, P. A., Budoff, M. J., Fischer, M. J., Rosas, S. E., Kanthety, R., Rahman, M., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.01.103 · Cited by 48
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Jang, Y., Waterworth, D. M., Lee, J.-E., Song, K. S., Kim, S., Kim, H.-S., Park, K. W., Cho, H., Oh, I., Park, J. E., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018208 · Cited by 47
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Pott, J., Schlegel, V., Teren, A., Horn, K., Kirsten, H., Blücher, C., Kratzsch, J., Loeffler, M., Thiery, J., Burkhardt, R., et al. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.117.001992 · Cited by 47
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Gälman, C., Matasconi, M., Persson, L., Parini, P., Angelin, B., & Rudling, M. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00166.2007 · Cited by 47
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Kantor, B., O’Donovan, B., Rittiner, J. E., Hodgson, D., Lindner, N., Guerrero, S., Dong, W., Zhang, A., & Chiba‐Falek, O. (2024) · Nature Communications · doi:10.1038/s41467-024-50515-6 · Cited by 48
Thomas, G. S., Wann, L. S., Allam, A. H., Thompson, R. C., Michalik, D. E., Sutherland, M. L., Sutherland, J. D., Lombardi, G. P., Watson, L., Cox, S. L., et al. (2014) · Global Heart · doi:10.1016/j.gheart.2014.04.002 · Cited by 46
Metadata
- Authors
- Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
- Howard Hughes Medical Institute (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-03-23
- Volume
- 354
- Issue
- 12
- Pages
- 1264-1272
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2067539811
- Semantic Scholar
- 5cb1ad66116f87a0743739413b3b5f7f633657f8
- Cited by
- 3,181
- References
- 27
- Citations by year
- 2026: 130 · 2025: 121 · 2024: 150 · 2023: 182 · 2022: 169 · 2021: 175 · 2020: 193 · 2019: 180 · 2018: 210 · 2017: 229 · 2016: 235 · 2015: 244 · 2014: 171 · 2013: 145 · 2012: 126
- FWCI
- 104.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- W. M. Keck Foundation
- Donald W. Reynolds Foundation
- National Institutes of Health (n01hc55021-47-0-1, n01hc55020-39-0-0, n01hc55016-37-0-0, n01hc055022-024, n01hc55019-35-0-1, n01hc55018-38-0-1, N01-HC55020, N01-HC-55021, HL20948, N01-HC-55019, N01-HC-55022, N01-HC55016, N01-HC55018, N01-HC-55015, n01hc55015-48-0-1)
- National Heart, Lung, and Blood Institute (N01-HC55022, N01-HC-55018, HL-20948, N01 HC 55020, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022, N01 HC 55019, N01-HC55016, P01HL020948, N01‐HC‐55015, N01-HC55021)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- PCSK9, LDL cholesterol, coronary artery disease, myocardial infarction, coronary revascularization, nonsense mutation, genetic variants, LDL cholesterol lowering, cardiovascular risk, Atherosclerosis Risk in Communities Study, black and white populations
- MeSH terms
- Proprotein Convertase 9, Black or African American, Carotid Arteries, Coronary Disease, Female, Gene Frequency, Genotype, Humans, Hypolipoproteinemias, Cholesterol, LDL, Male, Middle Aged, Risk, Serine Endopeptidases, United States, Genetic Variation, Cohort Studies, Incidence, Proportional Hazards Models, Codon, Nonsense, Proprotein Convertases, Black People, White People
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