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Does Lowering Low-Density Lipoprotein Cholesterol With Statin Restore Low Risk in Middle-Aged Adults? Analysis of the Observational MESA Study.

ABSTRACT: Background It is unclear if statin therapy in midlife can restore low cardiovascular risk in hypercholesterolemic individuals. Methods and Results At baseline, we grouped 5687 MESA (Multi-Ethnic Study of Atherosclerosis) participants aged ≥50 years without clinical cardiovascular disease (CVD) by Adult Treatment Panel III statin treatment recommendation and statin treatment status. We used Cox regression to compare the risks for coronary heart disease and CVD between the untreated group with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (reference) and other groups, adjusting for CVD risk factors. We also grouped participants by LDL-C level (< or ≥100 mg/dL), coronary artery calcium score (0 or >0 Agatston units), and statin status (untreated or treated) with the untreated LDL-C <100 mg/dL and coronary artery calcium=0 Agatston units as the reference. There were 567 coronary heart disease and 848 CVD events over 15 years of follow-up. The hazard ratios (HRs) for coronary heart disease and CVD in the group with statin-treated LDL-C <100 mg/dL were 1.16 (95% CI, 0.85-1.58) and 1.02 (95% CI, 0.78-1.32), respectively. However, participants with coronary artery calcium >0 Agatston units, treated to LDL-C <100 mg/dL had HRs of 2.6 (95% CI, 1.7-4.2) for coronary heart disease and 1.8 (95% CI, 1.2-2.6) for CVD. Conclusions Individuals treated with statins to LDL-C <100 mg/dL had similar levels of risk for atherosclerotic CVD as individuals with untreated LDL-C <100 mg/dL. However, individuals with coronary artery calcium >0 Agatston units have substantially higher risks despite lipid-lowering therapy, suggesting that statin treatment in midlife may not restore a low-risk state in primary prevention patients with established coronary atherosclerosis.

SUBMITTER: Liu K

PROVIDER: S-EPMC8483525 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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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Does Lowering Low-Density Lipoprotein Cholesterol With Statin Restore Low Risk in Middle-Aged Adults? Analysis of the Observational MESA Study.

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