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      Apolipoproteins A1, B, and apoB/apoA1 ratio are associated with first ST-segment elevation myocardial infarction but not with recurrent events during long-term follow-up

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          Abstract

          Introduction

          The current way to assess the risk of cardiovascular disease (CVD) is to measure conventional lipid and lipoprotein cholesterol fractions. Despite the success of statin treatment, residual cardiovascular risk remains high. Therefore, the value of extensive serum apolipoprotein (apo) profiling to assess the risk of ST-segment elevation myocardial infarction (STEMI) and of major adverse cardiac events (MACE) in patients with STEMI was investigated in a case–control design.

          Methods and results

          Serum apo levels were measured using liquid chromatography and mass spectrometry in 299 healthy individuals and 220 patients with STEMI. First, the association of apo profiles in baseline samples with risk of STEMI was examined, and second, the association of apo profiles at baseline with risk of recurrent MACE in patients with STEMI in a longitudinal study design was studied. High baseline (> 1.25 g/L) apoA1 levels were associated with a decreased risk of STEMI [odds ratio (OR) 0.17; 95% CI 0.11–0.26], whereas high apoB (> 1.00 g/L) levels (OR 2.17; 95% CI 1.40–3.36) and apoB/apoA1 ratio (OR per 1 SD (OR/SD): 2.16; 95% CI 1.76–2.65) were associated with an increased risk. Very-low-density-lipoprotein (VLDL)-associated apos gave conflicting results. Neither conventional lipid levels nor apo levels were associated with MACE in the STEMI group.

          Conclusion

          In conclusion, apoA1, apoB, and apoB/apoA1 were strongly associated with risk of STEMI. No clear relation between VLDL-associated apos and the risk of STEMI was found. Neither baseline serum apos nor lipids predicted MACE in statin-treated patients during long-term follow-up after a first STEMI.

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          Most cited references32

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          2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

          Supplemental Digital Content is available in the text.
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            Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

            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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              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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                Author and article information

                Contributors
                31-71-5265524 , m.c.bodde@lumc.nl
                Journal
                Clin Res Cardiol
                Clin Res Cardiol
                Clinical Research in Cardiology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1861-0684
                1861-0692
                8 October 2018
                8 October 2018
                2019
                : 108
                : 5
                : 520-538
                Affiliations
                [1 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Cardiology, C5-P, , Leiden University Medical Center, ; P.O. Box 9600, 2300 RC Leiden, The Netherlands
                [2 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Epidemiology, , Leiden University Medical Center, ; Leiden, The Netherlands
                [3 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Clinical Chemistry and Laboratory Medicine, , Leiden University Medical Center, ; Leiden, The Netherlands
                Author information
                http://orcid.org/0000-0003-1117-3188
                Article
                1381
                10.1007/s00392-018-1381-5
                6484771
                30298424
                6be18cef-396b-4592-a4ff-0fcc8adc5ac4
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.

                History
                : 17 July 2018
                : 27 September 2018
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Cardiovascular Medicine
                apolipoproteins,residual cardiovascular risk,quantitative proteomics,stemi

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