Abstract
Background: Low-density Lipoprotein Cholesterol (LDL-C) is a major Cardiovascular (CV) risk factor. Accumulating evidence supports a linear association between LDL-C levels and CV risk. However, the lower limit of LDL-C that might offer CV benefits without any safety concerns is still a topic of debate.
Objective: The purpose of this review is to present the safety of reducing LDL-C to low levels as it comes from major lipid-lowering drug studies, and to discuss data on several safety events that have been associated with low LDL-C levels.
Methods: A comprehensive literature search was performed to identify available data from clinical studies evaluating the association of low LDL-C with safety outcomes.
Results: Several large trials have evaluated the safety or reducing LDL-C to levels lower than 50 mg/dl or even lower than 25 mg/dl, more commonly with the use of a combination of statins with ezetimibe or proprotein convertase subtilisin kexin 9 inhibitors. In almost all trials, CV benefits were observed with LDL-C levels of 50 mg/dl or less compared with higher levels. In terms of safety, reduction of LDL-C to such levels was not associated with any significant adverse event. Of importance, cancer and hemorrhagic stroke incidences were not increased in patients attaining LDL-C lower than 40-50 mg/dl. Data regarding the impact of lowering LDL-C with neurocognitive disorders are contradictory; nevertheless, most studies stand in favor of neurocognitive safety with LDL-C reductions to low levels.
Conclusion: Achieving an LDL-C of 40-50 mg/dl seems to be safe, and importantly might offer CV beneficial effects. Data for attaining levels below 25 mg/dl is limited, however in favor of such reductions.
Keywords: Low-density lipoprotein cholesterol, safety, statins, PCSK9 inhibitors, cardiovascular disease, cancer.
Current Pharmaceutical Design
Title:Is very low LDL-C harmful?
Volume: 24 Issue: 31
Author(s): Charles Faselis*, Konstantinos Imprialos, Haris Grassos, Andreas Pittaras, Manolis Kallistratos and Athanasios Manolis
Affiliation:
- VA Medical Center and George Washington University, Washington, DC,United States
Keywords: Low-density lipoprotein cholesterol, safety, statins, PCSK9 inhibitors, cardiovascular disease, cancer.
Abstract: Background: Low-density Lipoprotein Cholesterol (LDL-C) is a major Cardiovascular (CV) risk factor. Accumulating evidence supports a linear association between LDL-C levels and CV risk. However, the lower limit of LDL-C that might offer CV benefits without any safety concerns is still a topic of debate.
Objective: The purpose of this review is to present the safety of reducing LDL-C to low levels as it comes from major lipid-lowering drug studies, and to discuss data on several safety events that have been associated with low LDL-C levels.
Methods: A comprehensive literature search was performed to identify available data from clinical studies evaluating the association of low LDL-C with safety outcomes.
Results: Several large trials have evaluated the safety or reducing LDL-C to levels lower than 50 mg/dl or even lower than 25 mg/dl, more commonly with the use of a combination of statins with ezetimibe or proprotein convertase subtilisin kexin 9 inhibitors. In almost all trials, CV benefits were observed with LDL-C levels of 50 mg/dl or less compared with higher levels. In terms of safety, reduction of LDL-C to such levels was not associated with any significant adverse event. Of importance, cancer and hemorrhagic stroke incidences were not increased in patients attaining LDL-C lower than 40-50 mg/dl. Data regarding the impact of lowering LDL-C with neurocognitive disorders are contradictory; nevertheless, most studies stand in favor of neurocognitive safety with LDL-C reductions to low levels.
Conclusion: Achieving an LDL-C of 40-50 mg/dl seems to be safe, and importantly might offer CV beneficial effects. Data for attaining levels below 25 mg/dl is limited, however in favor of such reductions.
Export Options
About this article
Cite this article as:
Faselis Charles *, Imprialos Konstantinos , Grassos Haris , Pittaras Andreas , Kallistratos Manolis and Manolis Athanasios , Is very low LDL-C harmful?, Current Pharmaceutical Design 2018; 24 (31) . https://dx.doi.org/10.2174/1381612824666181008110643
DOI https://dx.doi.org/10.2174/1381612824666181008110643 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Neuroprotective Properties of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) and its Lipid Ligands
Current Medicinal Chemistry Structure-Activity Relationship of Acetylcholinesterase Reactivators -Antidotes Against Nerve Agents
Letters in Organic Chemistry Bringing Light into the Diagnosis of Skin Disorders - Short Review on Laser Induced Fluorescence Spectroscopy and Optical Coherence Tomography in Dermatology
Current Medical Imaging Atorvastatin and Diabetic Vascular Complications
Current Pharmaceutical Design A Review of the Therapeutic Benefits of Moringa oleifera in Controlling High Blood Pressure (Hypertension)
Current Traditional Medicine Medicinal Properties of Mangiferin, Structural Features, Derivative Synthesis, Pharmacokinetics and Biological Activities
Mini-Reviews in Medicinal Chemistry Differences in Post-ischemic Motor Recovery and Angiogenesis of MCAO Rats Following Electroacupuncture at Different Acupoints
Current Neurovascular Research The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway
Current Molecular Medicine Body-centred and Object-centred Motor Imagery in Alzheimer's Disease
Current Alzheimer Research Oxidative Stress Genes, Antioxidants and Coronary Artery Disease in Type 2 Diabetes Mellitus
Cardiovascular & Hematological Agents in Medicinal Chemistry Resistant Hypertension in the Elderly-Second Line Treatments: Aldosterone Antagonists, Central Alpha-Agonist Agents, Alpha-Adrenergic Receptor Blockers, Direct Vasodilators, and Exogenous Nitric Oxide Donors
Cardiovascular & Hematological Agents in Medicinal Chemistry Neuro-Psychological Pattern in Patients Suffering from Primitive Dilated Cardiomyopathy with Impairment in Executive Function
Current Neurovascular Research Sepsis and Solid Organ Transplantation
Current Drug Targets Berberine Encapsulated PLGA-PEG Nanoparticles Modulate PCSK-9 in HepG2 Cells
Cardiovascular & Hematological Disorders-Drug Targets ACE2-Ang-(1-7)-Mas Axis in Brain: A Potential Target for Prevention and Treatment of Ischemic Stroke
Current Neuropharmacology Urinary Albumin to Creatinine Ratio as Potential Biomarker for Cerebral Microvascular Disease
Current Neurovascular Research Efficacy of Cannabis and its Constituents in Disease Management: Insights from Clinical Studies
Current Medicinal Chemistry Cardiovascular Effects of Phosphodiesterase 5 Inhibitors
Current Pharmaceutical Design Oral Appliances Improve Sleep Quality in Japanese Patients with Obstructive Sleep Apnea
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Osteoporosis Entwined with Cardiovascular Disease: The Implication of Osteoprotegerin and the Example of Statins
Current Medicinal Chemistry