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      Residual Risk Factors to Predict Major Adverse Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with and without Diabetes Mellitus

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          Abstract

          A prospective observational study was conducted to investigate the residual risk factors to predict recurrence of major adverse cardiovascular events (MACE) in atherosclerotic cardiovascular disease (ASCVD) patients with a high prevalence under lipid-lowering therapy, particularly in the subpopulations of diabetic and nondiabetic individuals. A total of 5,483 adults (with a mean age of 66.4 and 73.3% male) with established coronary heart disease, cerebrovascular disease, or peripheral artery disease were identified from the T-SPARCLE multi-center registry. Of them, 38.6% had diabetes. The residual risk factors for MACE are divergent in these atherosclerotic patients with and without diabetes. In diabetic subpopulation, the risk of MACE was significantly increased with heart failure (HF), chronic kidney disease (CKD) stage 4–5 (vs. stage 1–2), without beta blocker use, and higher non-HDL-C, after controlling for covariates including statin use and the intensity of therapy. Increased LDL-C and TG levels were also associated with increased risk, but to a much less extent. Among nondiabetic individuals, HF, CKD stage 4–5, and history of myocardial infarction were the significant independent predictors of MACE. It is suggested that ASCVD patients with concomitant diabetes need stricter control of lipid, particularly non-HDL-C levels, to reduce cardiovascular risk when on statin therapy.

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          A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk.

          Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial. This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed. All published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects model. Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44). The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C (P LDL-C (P LDL-C (P=0.017). Only HDL-C accounted for any substantial portion of the variance of the results among the studies. We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy. These results further validate the value of apoB in clinical care.
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            National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary.

            Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia.
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              Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges.

              This review captures the existence, cause, and treatment challenges of residual cardiovascular risk (CVR) after aggressive low-density lipoprotein cholesterol (LDL-C) reduction. Scientific evidence implicates low high-density lipoprotein cholesterol (HDL-C) and high triglycerides (TG) in the CVR observed after LDL-C lowering. However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial with fenofibrate, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) study with torcetrapib, and the recently terminated Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study with niacin, do not clearly attribute risk reduction value to HDL-C/TG modulation. The optimum approach to long-term lipid-modifying therapies for CVR reduction remains uncertain. Consequently, absolute risk modulation via lifestyle changes remains the centerpiece of a strategy addressing the physiologic drivers of CVR associated with HDL-C/TG, especially in the context of diabetes/metabolic syndrome.
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                Author and article information

                Contributors
                chauchungwu@ntu.edu.tw
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                23 August 2017
                23 August 2017
                2017
                : 7
                : 9179
                Affiliations
                [1 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Graduate Institute of Clinical Pharmacy, , College of Medicine, National Taiwan University, ; Taipei, Taiwan
                [2 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, School of Pharmacy, , College of Medicine, National Taiwan University, ; Taipei, Taiwan
                [3 ]ISNI 0000 0004 0572 7815, GRID grid.412094.a, Department of Pharmacy, , National Taiwan University Hospital, ; Taipei, Taiwan
                [4 ]ISNI 0000 0004 0637 1806, GRID grid.411447.3, Department of Medical Imaging and Radiological Sciences, , I-Shou University, ; Kaohsiung, Taiwan
                [5 ]ISNI 0000 0004 1797 2180, GRID grid.414686.9, Division of Cardiology, , Department of Internal Medicine, E-Da Hospital, ; Kaohsiung, Taiwan
                [6 ]ISNI 0000 0004 0572 7890, GRID grid.413846.c, Division of Cardiology, , Heart Center, Cheng-Hsin General Hospital, ; Taipei, Taiwan
                [7 ]ISNI 0000 0001 0425 5914, GRID grid.260770.4, School of Medicine, , National Yang-Ming University, ; Taipei, Taiwan
                [8 ]ISNI 0000 0004 1762 5613, GRID grid.452449.a, Mackay Memorial Hospital, , Mackay Medical College, ; New Taipei City, Taiwan
                [9 ]ISNI 0000 0004 0604 5314, GRID grid.278247.c, Department of Medical Research and Education, , Taipei Veterans General Hospital, ; Taipei, Taiwan
                [10 ]ISNI 0000 0001 0425 5914, GRID grid.260770.4, Institute of Pharmacology, , National Yang-Ming University, ; Taipei, Taiwan
                [11 ]ISNI 0000 0004 0572 7815, GRID grid.412094.a, Department of Internal Medicine (Cardiology Section), , National Taiwan University Hospital, ; Taipei, Taiwan
                [12 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Graduate Institute of Medical Education & Bioethics, , College of Medicine, National Taiwan University, ; Taipei, Taiwan
                Article
                8741
                10.1038/s41598-017-08741-0
                5569020
                28835613
                900ce39f-1247-410f-8402-14c78931617f
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 April 2017
                : 18 July 2017
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