Reducing LDL-Cholesterol to Very Low Levels: Sailing Between Established Benefits and Potential Risks. in High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension / High Blood Press Cardiovasc Prev. 2025 Mar;32(2):139-149. doi: 10.1007/s40292-025-00708-x. Epub 2025

2025
ASL Alessandria

Tipo pubblicazione

Review

Autori/Collaboratori (8)Vedi tutti...

Di Fusco SA
Clinical and Rehabilitation Cardiology Unit, Emergency Department, San Filippo Neri Hospital, ASL Rome 1, Rome, Italy. stefaniaa.difusco@aslroma1.it.
Volpe M
Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, Via Martinotti 20, 00135, Rome, Italy. stefaniaa.difusco@aslroma1.it.
Nardi F
Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035, 00189, Rome, Italy.

et alii...

Abstract

In view of the growing evidence supporting more marked reductions of low-density lipoprotein cholesterol (LDL-C), according to the concept of "the lower is better" and with the availability of powerful and well tolerated lipid-lowering drugs, physicians are facing today with the clinical management of patients with very low LDL-C levels. The fear of potential risks linked to extreme reductions of LDL-C down to very low levels may lead to the de-escalation of treatments with consequent paradoxical unfavorable consequences due to the exposure to a higher cardiovascular risk. The aim of this review is to point out evidence of very low LDL-C clinical impact, with a focus on potential adverse effects. Research on cholesterol homeostasis has identified complex mechanisms which guarantee cell functions even when circulating cholesterol levels are very low. The almost complete self-sufficiency of the human body in terms of cholesterol needs is confirmed by evidence derived from genetically determined models with very low LDL-C levels. Studies on the potential harm of lowering LDL-C to very low concentrations do not confirm an increased risk of cancer or neurodegenerative disease attributable to lipid-lowering treatments, whereas evidence suggests a potential benefit in these settings. A potential increased risk of hemorrhagic stroke has been reported, suggesting tight monitoring and control of blood pressure should be implemented in patients with very low LDL-C levels. With regard to statin treatment, a dose-dependent increased risk of newly diagnosed diabetes has been reported. This adverse effect has not been found with more recently approved lipid-lowering drugs.

Accesso banca dati bibliografica

PMID : 39998740

DOI : 10.1007/s40292-025-00708-x

Keywords

Humans; Cholesterol, LDL/blood; Risk Assessment; Biomarkers/blood; Treatment Outcome; Dyslipidemias/drug therapy/blood/diagnosis/epidemiology; Cardiovascular Diseases/prevention & control/epidemiology; Down-Regulation; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use/adverse effects; Risk Factors; Heart Disease Risk Factors; Anticholesteremic Agents/therapeutic use/adverse effects; Adverse effects; Cholesterol; LDL-C; Lipid-lowering treatment;