Cited by 276Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismDiabetes, Cardiovascular Risks, and Lipoproteins

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LDL cholesterol: controversies and future therapeutic directions

Ridker, Paul M·2014·The Lancet

DOI 10.1016/s0140-6736(14)61009-6

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Abstract

Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

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Specific recognition, intracellular assay and detoxification of fluorescent curcumin derivative for copper ions
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Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology
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6-Gingerol Regulates Hepatic Cholesterol Metabolism by Up-regulation of LDLR and Cholesterol Efflux-Related Genes in HepG2 Cells
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Conjugated linoleic acid regulates lipid metabolism through the expression of selected hepatic genes in laying hens
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MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice
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A Novel, Orally Bioavailable, Small-Molecule Inhibitor of PCSK9 With Significant Cholesterol-Lowering Properties In Vivo
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Recent advances in the understanding and care of familial hypercholesterolaemia: significance of the biology and therapeutic regulation of proprotein convertase subtilisin/kexin type 9
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Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice
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Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities
Beierlein, J. M., McNamee, L. M., Walsh, M. J., Kaitin, K. I., DiMasi, J. A., & Ledley, F. D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.06.001 · Cited by 24
“We note, however, that PCSK9 is a homologue within a large family of proprotein convertases that has been well studied(90) and that there is an extensive body of knowledge concerning the LDL receptor.(91) Research on both proprotein convertase and LDL receptors are well past the Te (Figure 9).”
Background

Authors: Ridker, P. M.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Ridker, Paul M
ORCID: Ridker, Paul M
Venue: The Lancet
Publisher: Elsevier BV
Published: 2014-08
Volume: 384
Issue: 9943
Pages: 607-617
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(14)61009-6
OpenAlex: W2058652637
Cited by: 274
References: 104
Citations by year: 2026: 7 · 2025: 23 · 2024: 13 · 2023: 20 · 2022: 13 · 2021: 14 · 2020: 25 · 2019: 22 · 2018: 31 · 2017: 29 · 2016: 35 · 2015: 38 · 2014: 4
FWCI: 6.67
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: LDL cholesterol, hyperlipidemia, statin therapy, LDL receptor, PCSK9 inhibitors, monoclonal antibodies, LDL cholesterol measurement, mass screening, treatment goals, cardiovascular risk, atherothrombotic complications
MeSH terms: Animals, Hypolipidemic Agents, Humans, Hypercholesterolemia, Cholesterol, LDL, Risk Factors, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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LDL cholesterol: controversies and future therapeutic directions

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