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      Elevated plasma lipoprotein(a) levels were associated with increased risk of cardiovascular events in Chinese patients with stable coronary artery disease

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          Abstract

          Recent studies have suggested that lipoprotein(a) [Lp(a)] is associated with cardiovascular disease (CVD). However, the contribution of Lp(a) to residual risk of CVD has not been determined in Chinese populations. We conducted a prospective study to evaluate the association between Lp(a) and the risk of major adverse cardiovascular events (MACEs) in patients with stable coronary artery disease (CAD) who received optimal medication treatment (OMT). The study enrolled 1602 patients with stable CAD from 5 hospitals in China. The baseline clinical characteristics and follow-up MACE data for the patients were recorded. Coronary lesion severity was assessed by the Gensini scoring system. All-cause death, non-fatal myocardial infarction, non-fatal stroke and unplanned coronary revascularization were considered MACEs. We found that plasma Lp(a) levels were positively associated with coronary lesion severity at baseline (p < 0.001). During a mean follow-up period of 39.6 months, 166 (10.4%) patients suffered MACEs. There were significant differences in the adjusted event-free survival rates among the Lp(a) quartile subgroups (p = 0.034). The hazard ratio for MACEs was 1.291 (95% confidence interval: 1.091–1.527, p = 0.003) per standardized deviation in the log-transformed Lp(a) level after adjustment for traditional cardiovascular risk factors. Therefore, Lp(a) was an independent predictor of MACEs in Chinese patients with stable CAD who received OMT.

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          Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

          Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations.
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            HDL and cardiovascular disease.

            The cholesterol contained within HDL is inversely associated with risk of coronary heart disease and is a key component of predicting cardiovascular risk. However, despite its properties consistent with atheroprotection, the causal relation between HDL and atherosclerosis is uncertain. Human genetics and failed clinical trials have created scepticism about the HDL hypothesis. Nevertheless, drugs that raise HDL-C concentrations, cholesteryl ester transfer protein inhibitors, are in late-stage clinical development, and other approaches that promote HDL function, including reverse cholesterol transport, are in early-stage clinical development. The final chapters regarding the effect of HDL-targeted therapeutic interventions on coronary heart disease events remain to be written. Copyright © 2014 Elsevier Ltd. All rights reserved.
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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
                zhaosp@csu.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 May 2018
                16 May 2018
                2018
                : 8
                : 7726
                Affiliations
                [1 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Department of Cardiology, The Second Xiangya Hospital, , Central South University, ; No. 139, Middle Renmin Road, Changsha, 410011 China
                [2 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Department of Endocrinology, The Second Xiangya Hospital, , Central South University, ; No. 139, Middle Renmin Road, Changsha, 410011 China
                Article
                25835
                10.1038/s41598-018-25835-5
                5955944
                29769559
                61811568-5c41-481e-9451-1d8dd6aa4ec3
                © The Author(s) 2018

                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 November 2017
                : 27 April 2018
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