The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 601–700 of 1,025
Human allelic variation: perspective from protein function, structure, and evolution
Jordan, D. M., Ramensky, V. E., & Sunyaev, S. R. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.03.006 · Cited by 77
Andersson, C., Lyass, A., Vasan, R. S., Massaro, J. M., D’Agostino, R. B., & Robins, S. J. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.08.007 · Cited by 76
Indices of Cholesterol Metabolism and Relative Responsiveness to Ezetimibe and Simvastatin
Gilchrist, S. C., Xu, F., Vega, G. L., Grundy, S. M., Chandalia, M., Lam, C., Lowe, R. S., Stepanavage, M. E., Musliner, T. A., Cohen, J. C., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1952 · Cited by 76
Self-citationFenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels
Troutt, J. S., Alborn, W. E., Cao, G., & Konrad, R. J. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m000620 · Cited by 76
Lipid-Modifying Agents, From Statins to PCSK9 Inhibitors
Preiss, D., Tobert, J. A., Hovingh, G. K., & Reith, C. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.072 · Cited by 75
Guidance for the diagnosis and treatment of hypolipidemia disorders
Bredefeld, C., Hussain, M. M., Averna, M. R., Black, D. D., Brin, M. F., Burnett, J. R., Charrière, S., Cuerq, C., Davidson, N. O., Deckelbaum, R. J., et al. (2022) · Journal of clinical lipidology · doi:10.1016/j.jacl.2022.08.009 · Cited by 75
Puri, R., Bansal, M., Mehta, V., Duell, P. B., Wong, N. D., Iyengar, S., Kalra, D. K., Nair, D. R., Nanda, N. C., Narula, J., et al. (2024) · Journal of clinical lipidology · doi:10.1016/j.jacl.2024.01.006 · Cited by 75
The genetic basis of familial hypercholesterolemia: inheritance, linkage, and mutations
Civeira, F. (2010) · The Application of Clinical Genetics · doi:10.2147/tacg.s8285 · Cited by 75
New Therapeutic Approaches to the Treatment of Dyslipidemia
Rader, D. J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.005 · Cited by 75
Oldoni, F., Baldassarre, D., Castelnuovo, S., Ossoli, A., Amato, M., van Capelleveen, J. C., Hovingh, G. K., de Groot, E., Bochem, A. E., Simonelli, S., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.034706 · Cited by 75
Peloso, G. M., Nomura, A., Khera, A. V., Chaffin, M. D., Won, H., Ardissino, D., Danesh, J., Schunkert, H., Wilson, J. G., Samani, N. J., et al. (2019) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.118.002376 · Cited by 75
Multiplex padlock targeted sequencing reveals human hypermutable CpG variationsPreprint
Li, J. B., Gao, Y., Aach, J., Zhang, K., Kryukov, G. V., Xie, B., Ahlford, A., Yoon, J.-K., Rosenbaum, A. M., Zaranek, A. W., et al. (2009) · Genome Research · doi:10.1101/gr.092213.109 · Cited by 75
Bayesian analysis of rare variants in genetic association studies
Yi, N., & Zhi, D. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20554 · Cited by 74
Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease
Welty, F. K. (2020) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000663 · Cited by 74
PCSK9 signaling pathways and their potential importance in clinical practice
Wiciński, M., Żak, J., Malinowski, B., Popek, G., & Grześk, G. (2017) · The EPMA Journal · doi:10.1007/s13167-017-0106-6 · Cited by 74
Tanigawa, Y., Li, J., Justesen, J. M., Horn, H., Aguirre, M., DeBoever, C., Chang, C. C., Narasimhan, B., Lage, K., Hastie, T. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11953-9 · Cited by 74
LRP6 Protein Regulates Low Density Lipoprotein (LDL) Receptor-mediated LDL Uptake
Ye, Z.-J., Go, G.-W., Singh, R., Liu, W., Keramati, A. R., & Mani, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.295287 · Cited by 73
Klose, G., Laufs, U., März, W., & Windler, E. E. T. (2014) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2014.0523 · Cited by 73
Comprehensive Assessment of Genotype Imputation Performance
Shi, S., Yuan, N., Yang, M. Y., Du, Z., Wang, J., Sheng, X., Wu, J., & Xiao, J. (2018) · Human Heredity · doi:10.1159/000489758 · Cited by 73
Majee, S., & Shit, G. C. (2020) · European Journal of Mechanics - B/Fluids · doi:10.1016/j.euromechflu.2020.04.004 · Cited by 73
Saavedra, Y. G. L., Day, R. W., & Seidah, N. G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.394023 · Cited by 73
Isolation and characterization of the circulating truncated form of PCSK9
Han, B., Eacho, P. I., Knierman, M. D., Troutt, J. S., Konrad, R. J., Yu, X., & Schroeder, K. M. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m049346 · Cited by 73
Early identification of cardiovascular risk using genomics and proteomics
Kullo, I. J., & Cooper, L. T. (2010) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.53 · Cited by 73
Complexity of mechanisms among human proprotein convertase subtilisin-kexin type 9 variants
Dron, J. S., & Hegele, R. A. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000386 · Cited by 72
Wang, Z., Zhu, S., Jia, Y., Wang, Y., Kubota, N., Fujiwara, N., Gordillo, R., Lewis, C., Zhu, M., Sharma, T., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.014 · Cited by 72
Kiezun, A., Pulit, S. L., Francioli, L. C., van Dijk, F., Swertz, M., Boomsma, D. I., van Duijn, C. M., Slagboom, P. E., van Ommen, G. J. B., Wijmenga, C., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003301 · Cited by 72
Konrad, R. J., Troutt, J. S., & Cao, G. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-38 · Cited by 72
Familial Hypercholesterolaemia Diagnosis and Management
Rodrigo Alonso, K., de Isla, L. P., Muñiz-Grijalvo, O., Díaz-Díaz, J. L., & Mata, P. (2018) · European Cardiology Review · doi:10.15420/ecr.2018:10:2 · Cited by 72
Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation
Rao, S., Yao, Y., & Bauer, D. E. (2021) · Genome Medicine · doi:10.1186/s13073-021-00857-3 · Cited by 72
Xu, W., Zhang, S., Qin, H., & Yao, K. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05957-3 · Cited by 74
Form to function: current and future roles for atherosclerosis imaging in drug development
Lindsay, A. C., & Choudhury, R. P. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2588 · Cited by 72
Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice
Luo, Y., Warren, L. C., Xia, D., Jensen, H., Sand, T. M., Petras, S. F., Qin, W., Miller, K. S., & Hawkins, J. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800542-jlr200 · Cited by 72
Ross, S. A., Anand, S. S., Joseph, P. G., & Paré, G. (2012) · JRSM Cardiovascular Disease · doi:10.1258/cvd.2012.012001 · Cited by 72
Blood pressure control and cardiovascular risk reduction.
Antonakoudis, G., Poulimenos, L. E., Kifnidis, K., Zouras, C., & Antonakoudis, H. (2007) · PubMed Central · Cited by 72
Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery
Zhou, K., Pedersen, H., Dawed, A. Y., & Pearson, E. R. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.51 · Cited by 72
Pharmacogenomics of statin response
Mangravite, L. M., & Krauss, R. M. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328235a5a2 · Cited by 72
American Diabetes Association Indications for Statins in Diabetes
Eldor, R., & Raz, I. (2009) · Diabetes Care · doi:10.2337/dc09-s345 · Cited by 71
Krarup, N. T., Borglykke, A., Allin, K. H., Sandholt, C. H., Justesen, J. M., Galijatovic, E. A. A., Grarup, N., Jørgensen, T., Pedersen, O. B., & Hansen, T. F. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.03.022 · Cited by 71
Liu, S., & Vaziri, N. D. (2013) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gft439 · Cited by 71
Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists
Zhang, Y., Ultsch, M. H., Skelton, N. J., Burdick, D. J., Beresini, M. H., Li, W., Kong-Beltran, M., Peterson, A. S., Quinn, J. G., Chiu, C., et al. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3453 · Cited by 71
Small Molecule Inhibitors of the PCSK9·LDLR Interaction
Taechalertpaisarn, J., Zhao, B., Liang, X., & Burgess, K. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.7b09360 · Cited by 71
How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol
Karagiannis, A. D., Mehta, A., Dhindsa, D. S., Virani, S. S., Orringer, C. E., Blumenthal, R. S., Stone, N. J., & Sperling, L. S. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa1080 · Cited by 70
The use of new CRISPR tools in cardiovascular research and medicine
Nishiga, M., Liu, C., Qi, L. S., & Wu, J. C. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00669-3 · Cited by 71
Wilkinson, M. J., Lepor, N. E., & Michos, E. D. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.028892 · Cited by 70
Cholesterol: The Good, the Bad, and the Ugly - Therapeutic Targets for the Treatment of Dyslipidemia
Elshourbagy, N. A., Meyers, H. V., & Abdel‐Meguid, S. S. (2013) · Medical Principles and Practice · doi:10.1159/000356856 · Cited by 70
Lowering LDL-cholesterol through diet: potential role in the statin era
Bruckert, É., & Rosenbaum, D. H. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328340b8e7 · Cited by 70
Characterization of novel mutations in the catalytic domain of the PCSK9 gene
Cameron, J., Holla, Ø. L., Laerdahl, J. K., Kulseth, M. A., Ranheim, T., Rognes, T., Berge, K. E., & Leren, T. P. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01915.x · Cited by 70
What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?
Humphries, S. E., Norbury, G., Leigh, S. E. A., Hadfield, S. G., & Nair, D. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32830636e5 · Cited by 70
Xu, X., Cui, Y., Cao, L., Zhang, Y., Yin, Y., & Hu, X. Y. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.4218 · Cited by 70
Roth, E. M., & McKenney, J. M. (2015) · Future Cardiology · doi:10.2217/fca.14.82 · Cited by 69
Whole genome sequence analysis of blood lipid levels in >66,000 individuals
Selvaraj, M. S., Li, X., Li, Z., Pampana, A., Zhang, D. Y., Park, J., Aslibekyan, S. W., Bis, J. C., Brody, J. A., Cade, B. E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33510-7 · Cited by 69
Self-citationMipomersen and other therapies for the treatment of severe familial hypercholesterolemia
Burnett, J., Bell, D. A., Hooper, & Watts, G. F. (2012) · Vascular Health and Risk Management · doi:10.2147/vhrm.s28581 · Cited by 69
Noh, H. J., Tang, R., Flannick, J. A., O'Dushlaine, C. T., Swofford, R., Howrigan, D. P., Genereux, D. P., Johnson, J., van Grootheest, G., Grünblatt, E., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00831-x · Cited by 69
Degradation of LDLR protein mediated by ‘gain of function’ PCSK9 mutants in normal and ARH cells
Fasano, T., Sun, X.-M., Patel, D., & Soutar, A. K. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.10.027 · Cited by 69
von Scheidt, M., Zhao, Y., de Aguiar Vallim, T. Q., Che, N., Wierer, M., Seldin, M. M., Franzén, O., Kurt, Z., Pang, S., Bongiovanni, D., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.050186 · Cited by 68
Standl, E., Schnell, O., McGuire, D. K., Ceriello, A., & Rydén, L. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30033-5 · Cited by 68
Cesaro, A., Bianconi, V., Gragnano, F., Moscarella, E., Fimiani, F., Monda, E., Scudiero, O., Limongelli, G., Pirro, M., & Calabrò, P. (2020) · BioFactors · doi:10.1002/biof.1619 · Cited by 68
Advances in biological therapies for dyslipidemias and atherosclerosis
Valanti, E.-K., Dalakoura-Karagkouni, K., Siasos, G., Kardassis, D., Eliopoulos, A. G., & Sanoudou, D. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154461 · Cited by 68
Polisecki, E. Y., Peter, I., Robertson, M., McMahon, A. D., Ford, I., Packard, C. J., Shepherd, J., Jukema, J. W., Blauw, G. J., Westendorp, R. G. J., et al. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.12.005 · Cited by 68
Burkart, K. M., Manichaikul, A. W., Wilk, J. B., Ahmed, F. S., Burke, G. L., Enright, P., Hansel, N. N., Haynes, D., Heckbert, S. R., Hoffman, E. A., et al. (2013) · European Respiratory Journal · doi:10.1183/09031936.00147612 · Cited by 68
Sniderman, A. D., Islam, S., McQueen, M., Pencina, M. J., Furberg, C. D., Thanassoulis, G., & Yusuf, S. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003665 · Cited by 68
Intensive LDL-cholesterol lowering therapy and neurocognitive function
Banach, M., Rizzo, M., Nikolić, D., Howard, G., Howard, V. J., & Mikhailidis (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.11.001 · Cited by 68
Hooper, A. J., Tang, X. L., & Burnett, J. R. (2024) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2024.2369747 · Cited by 68
PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology
Sundararaman, S. S., Döring, Y., & van der Vorst, E. P. C. (2021) · Biomedicines · doi:10.3390/biomedicines9070793 · Cited by 67
Postmus, I., Trompet, S., de Craen, A. J. M., Buckley, B. M., Ford, I., Stott, D. J., Sattar, N., Slagboom, P. E., Westendorp, R. G. J., & Jukema, J. W. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m033969 · Cited by 67
Lipid Management in Patients Presenting With Acute Coronary Syndromes: A Review
Claessen, B. E. P. M., Guedeney, P., Gibson, C. M., Angiolillo, D. J., Cao, D., Lepor, N. E., & Mehran, R. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.018897 · Cited by 67
Errata. PCSK9 function and physiology
Peterson, A. S., Fong, L. G., & Young, S. G. (2008) · Journal of Lipid Research · doi:10.1194/jlr.cx00001-jlr200 · Cited by 67
Mendelian randomisation applied to drug development in cardiovascular disease: a review
Mokry, L. E., Ahmad, O. S., Forgetta, V., Thanassoulis, G., & Richards, J. B. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102438 · Cited by 67
Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia
Huijgen, R., Fouchier, S. W., Denoun, M., Hutten, B. A., Vissers, M. N., Lambert, G. C., & Kastelein, J. J. P. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p023994 · Cited by 67
Vlachopoulos, C. V., Terentes-Printzios, D. G., Georgiopoulos, G. A., Skoumas, I., Koutagiar, I. P., Ioakeimidis, N., Stefanadis, C., & Tousoulis, D. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.07.922 · Cited by 67
Genetic-Driven Druggable Target Identification and Validation
Floris, M., Olla, S., Schlessinger, D., & Cucca, F. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.04.004 · Cited by 67
“Cholesterol-Years” for ASCVD Risk Prediction and Treatment
Shapiro, M. D., & Bhatt, D. L. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.08.004 · Cited by 67
Genome editing in cardiovascular diseases
Mani, I. (2021) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2021.01.021 · Cited by 66
Proprotein convertase subtilisin/kexin type 9 (PCSK9): A potential multifaceted player in cancer
Bhattacharya, A., Chowdhury, A., Chaudhury, K., & Shukla, P. C. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188581 · Cited by 66
Common and Low-Frequency Genetic Variants in the PCSK9 Locus Influence Circulating PCSK9 Levels
Chernogubova, E., Strawbridge, R. J., Mahdessian, H., Mälarstig, A., Krapivner, S., Gigante, B., Hellénius, M.-L., Fairé, U. D., Franco‐Cereceda, A., Syvänen, A.-C., et al. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.240549 · Cited by 66
Antisense Technology: An Emerging Platform for Cardiovascular Disease Therapeutics
Lee, R. G., Crosby, J. R., Baker, B. F., Graham, M. J., & Crooke, R. M. (2013) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-013-9495-7 · Cited by 66
New lipid-lowering drugs: an update
Wierzbicki, A. S., Hardman, T. C., & Viljoen, A. (2012) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2011.02867.x · Cited by 65
Smith, S. C., & Grundy, S. M. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.06.1159 · Cited by 65
Nicholls, S. J., Nissen, S. E., Prati, F., Windecker, S., Kataoka, Y., Puri, R., Hucko, T., Kassahun, H., Liao, J., Somaratne, R. M., et al. (2021) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-20-684 · Cited by 65
Mendelian randomization as a tool to inform drug development using human genetics
Daghlas, I., & Gill, D. (2023) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2023.5 · Cited by 65
Lee, C. J., Lee, Y., Park, S. W., Kim, K. J., Park, S., Youn, J., Lee, S., Kang, S., & Jang, Y. (2013) · Metabolism · doi:10.1016/j.metabol.2013.01.005 · Cited by 65
Implications of discoveries from genome-wide association studies in current cardiovascular practice
Jeemon, P. (2011) · World Journal of Cardiology · doi:10.4330/wjc.v3.i7.230 · Cited by 65
Statins and Their Effect on PCSK9—Impact and Clinical Relevance
Taylor, B. A., & Thompson, P. D. (2016) · Current Atherosclerosis Reports · doi:10.1007/s11883-016-0604-3 · Cited by 65
PCSK9 and diabetes: is there a link?
Momtazi‐Borojeni, A. A., Banach, M., Pirro, M., Stein, E. A., & Sahebkar, A. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.01.006 · Cited by 65
Interpreting the Clinical Implications of Drug-Target Mendelian Randomization Studies
Ference, B. A. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.06.007 · Cited by 65
Emerging therapeutic agents to lower lipoprotein (a) levels
Kolski, B. C., & Tsimikas, S. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283598d81 · Cited by 64
Future Use of Genomics in Coronary Artery Disease
Damani, S. B., & Topol, E. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.07.062 · Cited by 64
Chan, D. C., Lambert, G. C., Barrett, P. H. R., Rye, K., Ooi, E. M. M., & Watts, G. F. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2009.128645 · Cited by 64
Pećin, I., Hartgers, M. L., Hovingh, G. K., Dent, R. E., & Reiner, Ž. (2017) · European Journal of Preventive Cardiology · doi:10.1177/2047487317717346 · Cited by 64
Nishikido, T., & Ray, K. K. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00199 · Cited by 65
Miller, D. T., Ridker, P. M., Libby, P., & Kwiatkowski, D. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.12.045 · Cited by 64
Molecular genetics of atherosclerosis
Roy, H., Bhardwaj, S., & Ylä‐Herttuala, S. (2009) · Human Genetics · doi:10.1007/s00439-009-0654-5 · Cited by 64
Nordestgaard, B. G., & Tybjærg‐Hansen, A. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834477d2 · Cited by 64
Hegele, R. A., Gidding, S. S., Ginsberg, H. N., McPherson, R., Raal, F. J., Rader, D. J., Robinson, J. G., & Welty, F. K. (2015) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.306442 · Cited by 63
“Gain-of-function mutations in the PCSK9 gene cause autosomal-dominant hypercholesterolemia,(73) whereas loss-of-function mutations are associated with lower LDL cholesterol and reduced CVD risk.(21,74) Monoclonal antibodies (mAbs) against PCSK9 were recently approved in Europe and in North America.”
BackgroundThe genetic basis for adult onset glaucoma: Recent advances and future directions
Wang, Z., Wiggs, J. L., Aung, T., Khawaja, A. P., & Khor, C. C. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2022.101066 · Cited by 64
Arsenault, B. J. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac394 · Cited by 63
Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity
Deaton, A. M., Dubey, A., Ward, L. D., Dornbos, P., Flannick, J. A., Yee, E., Ticau, S., Noetzli, L. J., Parker, M. M., Hoffing, R. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31757-8 · Cited by 63
Tai, E. S., Sim, X., Ong, T. H., Wong, T. Y., Saw, S., Aung, T., Kathiresan, S., Orho‐Melander, M., Ordovás, J. M., Tan, J. T., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800456-jlr200 · Cited by 63
Update on Primary Hypobetalipoproteinemia
Hooper, A. J., & Burnett, J. R. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0423-3 · Cited by 63
Keebler, M., Sanders, C., Surti, A., Guiducci, C., Burtt, N. P., & Kathiresan, S. (2009) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.108.829473 · Cited by 63
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
