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      The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature

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          Abstract

          Background:

          Statins have long been used for the protection against coronary artery disease (CAD). Their beneficial effect apart from cholesterol reduction lies in their pleiotropic properties. Emerging evidence from laboratory studies and clinical trials as well have pointed out the pivotal role of inflammation on the initiation and exacerbation of atherosclerosis; a major cause of CAD. Inflam-mation markers such as high sensitivity C-reactive protein and adhesion molecules are shown to in-crease in CAD patients and are used as prognostic tools. It is well known that statins can actually re-duce the circulating levels of these agents slowing therefore the inflammatory process; interestingly not all types have the same outcome.

          Conclusion:

          The anti-inflammatory effect of statins on the formation of atherosclerotic plaque and the function of endothelial cells is thus of particular importance as these agents can actually ameliorate CAD prognosis

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          Most cited references55

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          Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

          A.G. Olsson, J McMurray, G Thorgeirsson … (1994)
          Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival. The present trial was designed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo. Over the 5.4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively. There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while noncardiovascular causes accounted for 49 and 46 deaths, respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin group had one or more major coronary events. The relative risk was 0.66 (95% CI 0.59-0.75, p < 0.00001), and the respective probabilities of escaping such events were 70.5% and 79.6%. This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularisation procedures. This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients.
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            Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.

            James Shepherd, Gerard J Blauw, Michael Murphy … (2002)
            Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke. We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat. Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability. Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.
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              Clinical application of growth factors and cytokines in wound healing.

              Stephan Barrientos, Harold Brem, Olivera Stojadinovic … (2014)
              Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy. © 2014 by the Wound Healing Society.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Curr Cardiol Rev
                Journal ID (iso-abbrev): Curr Cardiol Rev
                Journal ID (publisher-id): CCR
                Title: Current Cardiology Reviews
                Publisher: Bentham Science Publishers
                ISSN (Print): 1573-403X
                ISSN (Electronic): 1875-6557
                Publication date (Electronic): August 2017
                Publication date (Print): August 2017
                Volume: 13
                Issue: 3
                Pages: 209-216
                Affiliations
                [1]Department of Anatomy, School of Medicine, University of Athens , Athens, , Greece
                Author notes
                [* ]Address correspondence to this author at the Department of Anatomy, School of Medicine, University of Athens, 75 Mikras Asias Street, 
Athens 11527, Greece; Tel: 00302107462508; Fax: 00302107462398; 
E-mail: vaggelisd01@ 123456gmail.com
                Article
                Publisher ID: CCR-13-209
                DOI: 10.2174/1573403X13666170426104611
                PMC ID: 5633715
                PubMed ID: 28462692
                SO-VID: 3e7c5066-1290-49a3-af94-8e366ecb37cd
                Copyright © © 2017 Bentham Science Publishers
                License:

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                Date received : 23 January 2017
                Date revision received : 12 April 2017
                Date accepted : 17 April 2017
                Categories
                Subject: Article

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: statins,inflammation,pleiotropic effect,coronary artery disease,crp,cad prognosis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: statins, inflammation, pleiotropic effect, coronary artery disease, crp, cad prognosis

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