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      Effect of Plant Protein on Blood Lipids: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

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          Abstract

          Background

          There is a heightened interest in plant‐based diets for cardiovascular disease prevention. Although plant protein is thought to mediate such prevention through modifying blood lipids, the effect of plant protein in specific substitution for animal protein on blood lipids remains unclear. To assess the effect of this substitution on established lipid targets for cardiovascular risk reduction, we conducted a systematic review and meta‐analysis of randomized controlled trials using the Grading of Recommendations Assessment, Development, and Evaluation system.

          Methods and Results

          MEDLINE, EMBASE, and the Cochrane Registry were searched through September 9, 2017. We included randomized controlled trials of ≥3 weeks comparing the effect of plant protein in substitution for animal protein on low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, and apolipoprotein B. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences with 95% confidence intervals. Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 statistic). The overall quality (certainty) of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. One‐hundred twelve randomized controlled trials met the eligibility criteria. Plant protein in substitution for animal protein decreased low‐density lipoprotein cholesterol by 0.16 mmol/L (95% confidence interval, −0.20 to −0.12 mmol/L; P<0.00001; I 2=55%; moderate‐quality evidence), non–high‐density lipoprotein cholesterol by 0.18 mmol/L (95% confidence interval, −0.22 to −0.14 mmol/L; P<0.00001; I 2=52%; moderate‐quality evidence), and apolipoprotein B by 0.05 g/L (95% confidence interval, −0.06 to −0.03 g/L; P<0.00001; I 2=30%; moderate‐quality evidence).

          Conclusions

          Substitution of plant protein for animal protein decreases the established lipid targets low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, and apolipoprotein B. More high‐quality randomized trials are needed to improve our estimates.

          Clinical Trial Registration

          URL: http://www.clinicaltrials.gov. Unique identifier: NCT02037321.

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          Most cited references136

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          2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult.

          Many developments have occurred since the publication of the widely-used 2009 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines. Here, we present an updated version of the guidelines, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used, per present standards of the CCS. The total cardiovascular disease Framingham Risk Score (FRS), modified for a family history of premature coronary disease, is recommended for risk assessment. Low-density lipoprotein cholesterol remains the primary target of therapy. However, non-high density lipoprotein cholesterol has been added to apolipoprotein B as an alternate target. There is an increased emphasis on treatment of higher risk patients, including those with chronic kidney disease and high risk hypertension. The primary panel has recommended a judicious use of secondary testing for subjects in whom the need for statin therapy is unclear. Expanded information on health behaviours is presented and is the backbone of risk reduction in all subjects. Finally, a systematic approach to statin intolerance is advocated to maximize appropriate use of lipid-lowering therapy. This document presents the recommendations and principal conclusions of this process. Along with associated Supplementary Material that can be accessed online, this document will be part of a program of knowledge translation. The goal is to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dyslipidemia as a fundamental means of reducing global risk in the Canadian population. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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            Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT).

            The 356,222 men aged 35 to 57 years, who were free of a history of hospitalization for myocardial infarction, screened by the Multiple Risk Factor Intervention Trial (MRFIT) in its recruitment effort, constitute the largest cohort with standardized serum cholesterol measurements and long-term mortality follow-up. For each five-year age group, the relationship between serum cholesterol and coronary heart disease (CHD) death rate was continuous, graded, and strong. For the entire group aged 35 to 57 years at entry, the age-adjusted risks of CHD death in cholesterol quintiles 2 through 5 (182 to 202, 203 to 220, 221 to 244, and greater than or equal to 245 mg/dL [4.71 to 5.22, 5.25 to 5.69, 5.72 to 6.31, and greater than or equal to 6.34 mmol/L]) relative to the lowest quintile were 1.29, 1.73, 2.21, and 3.42. Of all CHD deaths, 46% were estimated to be excess deaths attributable to serum cholesterol levels 180 mg/dL or greater (greater than or equal to 4.65 mmol/L), with almost half the excess deaths in serum cholesterol quintiles 2 through 4. The pattern of a continuous, graded, strong relationship between serum cholesterol and six-year age-adjusted CHD death rate prevailed for nonhypertensive nonsmokers, nonhypertensive smokers, hypertensive nonsmokers, and hypertensive smokers. These data of high precision show that the relationship between serum cholesterol and CHD is not a threshold one, with increased risk confined to the two highest quintiles, but rather is a continuously graded one that powerfully affects risk for the great majority of middle-aged American men.
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              The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease.

              Anon. (1984)
              The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), a multicenter, randomized, double-blind study, tested the efficacy of cholesterol lowering in reducing risk of coronary heart disease (CHD) in 3,806 asymptomatic middle-aged men with primary hypercholesterolemia (type II hyperlipoproteinemia). The treatment group received the bile acid sequestrant cholestyramine resin and the control group received a placebo for an average of 7.4 years. Both groups followed a moderate cholesterol-lowering diet. The cholestyramine group experienced average plasma total and low-density lipoprotein cholesterol (LDL-C) reductions of 13.4% and 20.3%, respectively, which were 8.5% and 12.6% greater reductions than those obtained in the placebo group. The cholestyramine group experienced a 19% reduction in risk (p less than .05) of the primary end point--definite CHD death and/or definite nonfatal myocardial infarction--reflecting a 24% reduction in definite CHD death and a 19% reduction in nonfatal myocardial infarction. The cumulative seven-year incidence of the primary end point was 7% in the cholestyramine group v 8.6% in the placebo group. In addition, the incidence rates for new positive exercise tests, angina, and coronary bypass surgery were reduced by 25%, 20%, and 21%, respectively, in the cholestyramine group. The risk of death from all causes was only slightly and not significantly reduced in the cholestyramine group. The magnitude of this decrease (7%) was less than for CHD end points because of a greater number of violent and accidental deaths in the cholestyramine group. The LRC-CPPT findings show that reducing total cholesterol by lowering LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of raised LDL-C levels. This clinical trial provides strong evidence for a causal role for these lipids in the pathogenesis of CHD.
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                Author and article information

                Contributors
                john.sievenpiper@utoronto.ca
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                20 December 2017
                December 2017
                : 6
                : 12 ( doiID: 10.1002/jah3.2017.6.issue-12 )
                : e006659
                Affiliations
                [ 1 ] Toronto 3D Knowledge Synthesis and Clinical Trials Unit Clinical Nutrition and Risk Factor Modification Centre St. Michael's Hospital Toronto Ontario Canada
                [ 2 ] Division of Endocrinology and Metabolism St. Michael's Hospital Toronto Ontario Canada
                [ 3 ] Li Ka Shing Knowledge Institute St. Michael's Hospital Toronto Ontario Canada
                [ 4 ] School of Medicine Faculty of Health Sciences Queen's University Kingston Ontario Canada
                [ 5 ] Department of Nutritional Sciences Faculty of Medicine University of Toronto Ontario Canada
                [ 6 ] Department of Medicine Faculty of Medicine University of Toronto Ontario Canada
                [ 7 ] Departments of Health Research Methods, Evidence, and Impact Faculty of Health Sciences McMaster University Hamilton Ontario Canada
                [ 8 ] College of Pharmacy and Nutrition University of Saskatchewan Saskatoon Saskatchewan Canada
                Author notes
                [*] [* ] Correspondence to: John L. Sievenpiper, MD, PhD, FRCPC Toronto 3D Knowledge Synthesis and Clinical Trials Unit, St. Michael's Hospital, 6137‐61 Queen St E, Toronto, ON, Canada M5C 2T2. E‐mail: john.sievenpiper@ 123456utoronto.ca
                Article
                JAH32821
                10.1161/JAHA.117.006659
                5779002
                29263032
                9cdf6476-fee5-4b31-b208-1421983c1e11
                © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 18 May 2017
                : 06 November 2017
                Page count
                Figures: 2, Tables: 1, Pages: 15, Words: 14449
                Funding
                Funded by: Canadian Institutes of Health Research
                Award ID: 129920
                Funded by: Canada Foundation for Innovation
                Funded by: Ministry of Research and Innovation's Ontario Research Fund
                Funded by: Government of Canada
                Funded by: PSI Graham Farquharson Knowledge Translation Fellowship
                Funded by: Canadian Diabetes Association
                Funded by: CIHR INMD/Canadian Nutrition Society New Investigator Partnership Prize
                Funded by: Banting & Best Diabetes Centre Sun Life Financial New Investigator Award
                Funded by: Toronto 3D Knowledge Synthesis and Clinical Trials Foundation Internship Award
                Categories
                Systematic Review and Meta‐Analysis
                Systematic Review and Meta‐Analysis
                Custom metadata
                2.0
                jah32821
                December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.8 mode:remove_FC converted:27.12.2017

                Cardiovascular Medicine
                animal protein,cholesterol,dyslipidemia,lipids,meta‐analysis,protein,soy,systematic review,vegetable protein,lipids and cholesterol,meta analysis

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