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Low Levels of Low-Density Lipoprotein Cholesterol and Endothelial Function in Subjects without Lipid-Lowering Therapy.

ABSTRACT: An elevation of serum low-density lipoprotein cholesterol (LDL-C) levels has been associated with endothelial dysfunction in statin naïve subjects. However, there is no information on endothelial function in subjects with extremely low levels of LDL-C. The purpose of the present study was to determine the relationship of LDL-C levels, especially low levels of LDL-C, with endothelial function. Endothelial function assessed by flow-mediated vasodilation (FMD) measurement and LDL-C levels were evaluated in 7120 subjects without lipid-lowering therapy. We divided the subjects into five groups by LDL-C levels: <70 mg/dL, 70-99 mg/dL, 100-119 md/dL, 120-139 mg/dL, and ?140 mg/dL. FMD values were significantly smaller in subjects with LDL-C levels of ?140 mg/dL than in those with LDL-C levels of 70-99 mg/dL and 100-119 mg/dL (p < 0.001 and p = 0.004, respectively). The FMD values in the LDL-C of <70 mg/dL group were not significantly different from those in the other groups. To evaluate the relationship of extremely low LDL-C levels with endothelial function, we divided the subjects with LDL-C of <70 mg/dL into those with LDL-C levels of <50 mg/dL and 50-69 mg/dL. FMD values were similar in the LDL-C <50 mg/dL group and ?50 mg/dL group in the propensity score-matched population (p = 0.570). A significant benefit was not found in subjects with low LDL-C levels from the aspect of endothelial function.

SUBMITTER: Takaeko Y

PROVIDER: S-EPMC7761134 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Low Levels of Low-Density Lipoprotein Cholesterol and Endothelial Function in Subjects without Lipid-Lowering Therapy.

Takaeko Yuji Y Kajikawa Masato M Kishimoto Shinji S Yamaji Takayuki T Harada Takahiro T Han Yiming Y Kihara Yasuki Y Hida Eisuke E Chayama Kazuaki K Goto Chikara C Aibara Yoshiki Y Yusoff Farina Mohamad FM Maruhashi Tatsuya T Nakashima Ayumu A Higashi Yukihito Y

Journal of clinical medicine 20201124 12

An elevation of serum low-density lipoprotein cholesterol (LDL-C) levels has been associated with endothelial dysfunction in statin naïve subjects. However, there is no information on endothelial function in subjects with extremely low levels of LDL-C. The purpose of the present study was to determine the relationship of LDL-C levels, especially low levels of LDL-C, with endothelial function. Endothelial function assessed by flow-mediated vasodilation (FMD) measurement and LDL-C levels were eval ...[more]

PMID: 33255270

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Project description:Purpose of reviewThe primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein-cholesterol (LDL-C) lowering. Typically, statin therapy remains the first line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline.Recent findingsNovel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still on-going. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and anti-sense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation.SummaryRecently several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

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Dataset Information

Low Levels of Low-Density Lipoprotein Cholesterol and Endothelial Function in Subjects without Lipid-Lowering Therapy.

Publications

Low Levels of Low-Density Lipoprotein Cholesterol and Endothelial Function in Subjects without Lipid-Lowering Therapy.

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