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      Cholesterol, carotid artery disease and stroke: what the vascular specialist needs to know

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          Abstract

          Hypercholesterolemia is a risk factor for carotid artery stenosis and stroke. Statins are the main drugs for the management of hypercholesterolemia and they are strongly recommended by international guidelines for the management of vascular patients. The present review will focus on the associations between cholesterol, carotid artery stenosis and stroke and will cover several topics, including the conservative and perioperative/periprocedural management of carotid patients, the effect of statins on contrast-induced nephropathy developing after endovascular carotid interventions, the role of statin loading prior to endovascular procedures, as well as the indirect beneficial effects of statin treatment on renal function. It will also discuss the topics of statin intolerance and alternative cholesterol-lowering options for statin-intolerant vascular patients. Cholesterol levels play a prognostic role in carotid patients with regards to both short- and long-term stroke and mortality rates. Physicians should keep in mind the pivotal role of cholesterol levels in determining cardiovascular outcomes and the pleiotropic beneficial effects associated with statin use and should not miss the opportunity for cardiovascular risk reduction with aggressive statin treatment.

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          Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

          Marc Sabatine, Robert Giugliano, Anthony Keech … (2017)
          Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.
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            Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials

            Cholesterol Treatment Trialists' (CTT) Collaboration, Aldo Pietro Maggioni (2011)
            Summary Background Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy. Methods We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation. Findings In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations. Interpretation Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%. Funding UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.
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              2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

              Stephan Windecker, Philippe Kolh, Fernando Alfonso … (2014)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ann Transl Med
                Journal ID (iso-abbrev): Ann Transl Med
                Journal ID (publisher-id): ATM
                Title: Annals of Translational Medicine
                Publisher: AME Publishing Company
                ISSN (Print): 2305-5839
                ISSN (Electronic): 2305-5847
                Publication date (Print and electronic): October 2020
                Publication date (Print): October 2020
                Volume: 8
                Issue: 19
                Electronic Location Identifier: 1265
                Affiliations
                [1 ]Department of General and Vascular Surgery, Central Clinic of Athens , Athens, Greece;
                [2 ]Division of Vascular Surgery, New York University Langone Medical Center, NY, USA;
                [3 ]Division of Vascular Surgery, The Cleveland Clinic , Cleveland, OH, USA;
                [4 ]Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich , Munich, Germany;
                [5 ]Department of Clinical Research, University of Poitiers, CHU de Poitiers, Poitiers, France;
                [6 ]Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL) , London, UK
                Author notes

                Contributions: (I) Conception and design: KI Paraskevas; (II) Administrative support: DP Mikhailidis; (III) Provision of study materials or patients: KI Paraskevas, FJ Veith, HH Eckstein; (IV) Collection and assembly of data: KI Paraskevas, DP Mikhailidis, JB Ricco; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Kosmas I. Paraskevas, MD, Department of General and Vascular Surgery, Central Clinic of Athens, 24, Alex. Papagou street, N. Iraklio 14122, Athens, Greece. Email: paraskevask@ 123456hotmail.com .
                Article
                Publisher ID: atm-08-19-1265
                DOI: 10.21037/atm.2020.02.176
                PMC ID: 7607102
                PubMed ID: 33178797
                SO-VID: f3b9024f-54e0-43f1-a526-e551abfe14ef
                Copyright © 2020 Annals of Translational Medicine. All rights reserved.
                License:

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                Date received : 17 December 2019
                Date accepted : 20 February 2020
                Categories
                Subject: Review Article on Carotid Artery Stenosis and Stroke: Prevention and Treatment Part I

                Keywords: cholesterol,statins,carotid artery stenosis,stroke
                Data availability:
                Keywords: cholesterol, statins, carotid artery stenosis, stroke

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