Major Lipids, Apolipoproteins, and Risk of Vascular Disease
TL;DR: Estimates of the associations of major lipids and apolipoproteins in relation to coronary heart disease (CHD) and ischemic stroke are produced, incorporating adjustment for confounding caused by other risk factors and correction for regression dilution.
Abstract: RELIABLE ASSESSMENT OF THE separate and joint associations of major blood lipids and apolipoproteins with the risk of vascular disease is important for the development of screening and therapeutic strategies. Expert opinion is divided about whether assessment of apolipoprotein AI (apo AI) and apolipoprotein B (apo B) should replace assessment of high-density lipoprotein cholesterol (HDL-C) and total cholesterol levels in assessment of vascular risk. Althoughthere isagreementabout the valueofreducinglow-densitylipoprotein cholesterol (LDL-C or, approximately analogously,non–high-density lipoprotein cholesterol [non–HDL-C]), uncertainty persists about the merits of modification or measurement of triglycerides orHDL-C.Therearestronglypositiveepidemiological associationsof triglyceride concentration with risk of vascular disease, but it is not clear to what extent theserelationshipsdependoncholesterol levels or vary with fasting state. Similarly, although previous analyses have generally reported inverse associations of HDL-C with risk of vascular disease, many studies have not investigated the extent to which they depend on triglyceride concentration. The failure of torcetrapib has raised questions about the value of raising HDL-C and highlighted the need to characterize more reliably the relationship between HDL-C and vascular risk, particularly at high HDL-C levels. Different uncertainties apply in relation to the risk of ischemic stroke and the cholesterol content of proatherogenic lipoproteins. The reduction in ischemic stroke in randomized trials of statins (which principally lower LDL-C) is remarkable in light of the weak epidemiological association reported between circulating LDL-C concentration and ischemic stroke, suggesting the need for more powerful and detailed prospective analyses of blood lipids and stroke subtypes. The objective of this report is to produce reliable estimates of the associations of major lipids and apolipoproteins in relation to coronary heart disease (CHD) and ischemic stroke, incorporating adjustment for confounding caused by other risk factors and correction for regression dilution.
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TL;DR: March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.
Abstract: March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
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TL;DR: This year's edition of the Statistical Update includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association’s 2020 Impact Goals.
Abstract: Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...
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TL;DR: Harmon S. Jordan, ScD, Lev Nevo, MD, Janusz Wnek, PhD Jeffrey L. Anderson,MD, FACC, FAHA, Chair-Elect, Nancy M. Halperin, PhD.
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TL;DR: The ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute and stakeholder and professional organizations to develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health.
Abstract: Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S50
The goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop …
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Cites background or methods from "Major Lipids, Apolipoproteins, and ..."
...5 Emerging Risk Factors Collaboration (41) ApoB This paper provided evidence of rough equivalence of associations of CVD with non-HDL–C and ApoB after multivariable adjustment (including HDL–C)....
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...Summary of Systematic Reviews and Meta-Analyses for CQ1 Thirteen systematic review articles or meta-analyses met the inclusion/exclusion criteria (9-18,41-43)....
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TL;DR: A novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate is presented, which is consistent even when up to 50% of the information comes from invalid instrumental variables.
Abstract: Developments in genome-wide association studies and the increasing availability of summary genetic association data have made application of Mendelian randomization relatively straightforward. However, obtaining reliable results from a Mendelian randomization investigation remains problematic, as the conventional inverse-variance weighted method only gives consistent estimates if all of the genetic variants in the analysis are valid instrumental variables. We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate. This estimator is consistent even when up to 50% of the information comes from invalid instrumental variables. In a simulation analysis, it is shown to have better finite-sample Type 1 error rates than the inverse-variance weighted method, and is complementary to the recently proposed MR-Egger (Mendelian randomization-Egger) regression method. In analyses of the causal effects of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol on coronary artery disease risk, the inverse-variance weighted method suggests a causal effect of both lipid fractions, whereas the weighted median and MR-Egger regression methods suggest a null effect of high-density lipoprotein cholesterol that corresponds with the experimental evidence. Both median-based and MR-Egger regression methods should be considered as sensitivity analyses for Mendelian randomization investigations with multiple genetic variants.
2,959 citations
Cites background from "Major Lipids, Apolipoproteins, and ..."
...LDL-c is observationally positively associated with CAD risk (Di Angelantonio et al., 2009)....
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References
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TL;DR: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented and comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99.
Abstract: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented. The method involves measurements of fasting plasma total cholesterol, triglyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, depending on the patient population compared.
30,622 citations
TL;DR: Dairy therapy remains the first line of treatment of high blood cholesterol, and drug therapy is reserved for patients who are considered to be at high risk for CHD, and the fundamental approach to treatment is comparable.
Abstract: THE SECOND report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II, or ATP II) presents the National Cholesterol Education Program's updated recommendations for cholesterol management. It is similar to the first in general outline, and the fundamental approach to treatment of high blood cholesterol is comparable. This report continues to identify low-density lipoproteins (LDL) as the primary target of cholesterol-lowering therapy. As in the first report, the second report emphasizes the role of the clinical approach in primary prevention of coronary heart disease (CHD). Dietary therapy remains the first line of treatment of high blood cholesterol, and drug therapy is reserved for patients who are considered to be at high risk for CHD. However, the second report contains new features that distinguish it from the first. These include the following: Increased emphasis on See also pp 3002 and 3009.
28,495 citations
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Abstract: The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.
25,460 citations
"Major Lipids, Apolipoproteins, and ..." refers methods in this paper
...) Hazard ratios were adjusted progressively for age, sex, systolic blood pressure, smoking status, history of diabetes, body mass index, and lipid measures, with the evidence of association indicated by the Wald 2 statistic and heterogeneity between studies assessed by the I(2) statistic.(17) Investigation of effect modification was quantified by formal tests of interaction....
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TL;DR: Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics.
6,396 citations
TL;DR: In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events.
Abstract: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. Methods We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Results The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. Conclusions
5,547 citations