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      Longitudinal Changes in Cholesterol Efflux Capacities in Patients With Coronary Artery Disease Undergoing Lifestyle Modification Therapy

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          Abstract

          Background

          Our objective was to identify the determinants of high‐density lipoprotein cholesterol efflux capacity ( HDLCEC) changes in patients with coronary artery disease who participated in a lifestyle modification program aimed at increasing physical activity levels and improving diet quality.

          Methods and Results

          A total of 86 men with coronary artery disease aged between 35 and 80 years participated in a 1‐year lifestyle modification program that aimed to achieve a minimum of 150 minutes of aerobic physical activity weekly and improve diet quality. HDLCECs were measured before and after the 1‐year intervention using 3H‐cholesterol–labeled J774 and HepG2 cells. Visceral, subcutaneous, and cardiac adipose tissue levels were assessed before and after the intervention using magnetic resonance imaging. Lipoprotein particle size and concentrations were measured by proton nuclear magnetic resonance spectroscopy and a complete lipoprotein‐lipid profile was obtained. At baseline, the best correlate of HDLCECs were apolipoprotein AI ( R 2=0.35, P<0.0001) and high‐density lipoprotein cholesterol ( R 2=0.21, P<0.0001) for J774‐ HDLCECs and HepG2‐ HDLCECs, respectively. Baseline and longitudinal changes in HDLCECs were associated with several lipoprotein size and concentration indices, although high‐density lipoprotein cholesterol was the best predictor of longitudinal changes in J774‐ HDLCECs ( R 2=0.18, P=0.002) and apolipoprotein AI was found to be the best predictor of longitudinal changes in HepG2 cholesterol efflux capacities ( R 2=0.21, P=0.002).

          Conclusions

          Results of this study suggest that increases in high‐density lipoprotein cholesterol and apolipoprotein AI levels typically observed in patients with coronary artery disease undergoing healthy lifestyle modification therapy may be indicative of higher plasma concentrations of functional high‐density lipoprotein particles.

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          Most cited references36

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          The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.

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            Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy.

            Laboratory measurements of plasma lipids (principally cholesterol and triglycerides) and lipoprotein lipids (principally low-density lipoprotein [LDL] and low-density lipoprotein [HDL] cholesterol) are the cornerstone of the clinical assessment and management of atherosclerotic cardiovascular disease (CVD) risk. LDL particles, and to a lesser extent very-low-density lipoprotein [VLDL] particles, cause atherosclerosis, whereas HDL particles prevent or reverse this process through reverse cholesterol transport. The overall risk for CVD depends on the balance between the "bad" LDL (and VLDL) and "good" HDL particles. Direct assessment of lipoprotein particle numbers us now possible through nuclear magnetic resonance spectroscopic analysis.
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              HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment

              Aims Niacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. Methods and results Prior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for ∼1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25% of participants allocated ERN/LRPT vs. 17% allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6–7.5; P 3× upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10%/year) ERN/LRPT vs. 30 (0.06%/year) placebo allocated participants. Conclusion The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ∼1 month, three-quarters continued to take it for ∼4 years.
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                Author and article information

                Contributors
                benoit.arsenault@criucpq.ulaval.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
                01 June 2018
                05 June 2018
                : 7
                : 11 ( doiID: 10.1002/jah3.2018.7.issue-11 )
                : e008681
                Affiliations
                [ 1 ] Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec Canada
                [ 2 ] Department of Medicine Faculty of Medicine Université Laval Québec Canada
                [ 3 ] Department of Kinesiology Faculty of Medicine Université Laval Québec Canada
                [ 4 ] Faculty of Pharmacy Université Laval Québec Canada
                [ 5 ] Center for Lipid Metabolomics Divisions of Preventive and Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA
                [ 6 ] Department of Surgery Faculty of Medicine Université Laval Québec Canada
                Author notes
                [*] [* ] Correspondence to: Benoit J. Arsenault, PhD, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Y‐3106, Pavillon Marguerite D'Youville, 2725 chemin Ste‐Foy, Québec, Canada G1V 4G5. E‐mail: benoit.arsenault@ 123456criucpq.ulaval.ca
                Article
                JAH33245
                10.1161/JAHA.118.008681
                6015361
                29858367
                46fe8a54-5a58-4c59-bfb8-f72ea79372c6
                © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 January 2018
                : 02 May 2018
                Page count
                Figures: 8, Tables: 5, Pages: 15, Words: 8881
                Funding
                Funded by: Canadian Institutes of Health Research
                Award ID: 161971
                Funded by: Banting Research Foundation
                Funded by: Fonds de recherche du Québec: Santé
                Funded by: National Institutes of Health
                Award ID: HL117861
                Award ID: HL134811
                Award ID: DK 112940
                Categories
                Original Research
                Original Research
                Preventive Cardiology
                Custom metadata
                2.0
                jah33245
                05 June 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.0 mode:remove_FC converted:05.06.2018

                Cardiovascular Medicine
                adipose tissue,cholestrol efflux capacity,coronary artery disease,lifestyle,lipids and lipoproteins,risk factors,cardiovascular disease,lipids and cholesterol

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