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Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab.
NEJM Evid
January 2025
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston.
Background: Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown.
Methods: This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension.
Type 2 diabetes genetic risk and incident diabetes across diabetes risk enhancers.
Diabetes Obes Metab
December 2024
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Aims: To evaluate the predictive value of a contemporary type 2 diabetes (T2D) polygenic score (PGS) in detecting incident diabetes across a range of diabetes risk factors.
Materials And Methods: We analysed participants in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial (ClinicalTrials.gov, number NCT0176463), which compared the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab versus placebo in lowering cardiovascular outcomes in participants with stable atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL (1.
Isosteric 3D Bicyclo[1.1.1]Pentane (BCP) Core-Based Lipids for mRNA Delivery and CRISPR/Cas Gene Editing.
J Am Chem Soc
December 2024
Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, United States.
Lipid nanoparticles (LNPs) are an essential component of messenger RNA (mRNA) vaccines and genome editing therapeutics. Ionizable amino lipids, which play the most crucial role in enabling mRNA to overcome delivery barriers, have, to date, been restricted to two-dimensional (2D) architectures. Inspired by improved physicochemical properties resulting from the incorporation of three-dimensionality (3D) into small-molecule drugs, we report the creation of 3D ionizable lipid designs through the introduction of bicyclo[1.
View Article and Find Full Text PDFAssociation of PCSK9 inhibitors with risk of nonmelanoma skin cancer: a retrospective cohort study.
Br J Dermatol
November 2024
Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.
Background: Growing evidence has shown that cholesterol metabolism abnormalities involve carcinogenesis. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have been reported to inhibit tumor progression and prevent ultraviolet-related skin damage.
Objective: To investigate the association of PCSK9 inhibitors with the risk of nonmelanoma skin cancer (NMSC).
Fluorescent gold nanoclusters possess multiple actions against atherosclerosis.
Redox Biol
December 2024
Cardiovascular Center, Department of Internal Medicine, and Department of Medical Research, MacKay Memorial Hospital, Taipei, 10449, Taiwan. Electronic address:
Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles.
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