Lipids and Lipoproteins and Risk of Different Vascular Events in the MRC/BHF Heart Protection Study

Published on May 22, 2012in Circulation 18.88
· DOI :10.1161/CIRCULATIONAHA.111.073684
S Parish54
Estimated H-index: 54
(Clinical Trial Service Unit),
Alison Offer7
Estimated H-index: 7
(Clinical Trial Service Unit)
+ 5 AuthorsRory Collins128
Estimated H-index: 128
(Clinical Trial Service Unit)
Background—Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol are established risk factors for vascular disease, but lipoprotein particle concentrations may be stronger determinants of risk. Methods and Results—Associations between vascular events and baseline concentrations of cholesterol fractions, apolipoproteins B and A1, and lipoprotein particles assessed by nuclear magnetic resonance were considered in the Heart Protection Study randomized trial of simvastatin versus placebo (>5000 vascular events during 5.3 years of follow-up among 20 000 participants). Major occlusive coronary events were equally strongly associated with the cholesterol- and particle-based total LDL measures; adjusted hazard ratios per 1-SD-higher level were 1.25 (95% confidence interval [CI], 1.16–1.34) for LDL cholesterol, 1.22 (95% CI, 1.14–1.32) for non–HDL cholesterol, 1.23 (95% CI, 1.15–1.33) for apolipoprotein B, and 1.25 (95% CI, 1.16–1.35) for LDL particle number. Given the total LDL ...
  • References (39)
  • Citations (130)
Published on Jan 1, 2002in The Lancet 53.25
Salim Yusuf Mb Bs DPhil Frcpc182
Estimated H-index: 182
Background Throughout the usual LDL cholesterol range in Western populations, lower blood concentrations are associated with lower cardiovascular disease risk. In such populations, therefore, reducing LDL cholesterol may reduce the development of vascular disease, largely irrespective of initial cholesterol concentrations. Methods 20 536 UK adults (aged 40-80 years) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive 40 mg simvastatin daily (av...
5,820 Citations
Published on Dec 1, 2007in The Lancet 53.25
Sarah Lewington41
Estimated H-index: 41
Gary Whitlock26
Estimated H-index: 26
+ 6 AuthorsRory Collins128
Estimated H-index: 128
Background Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors. Methods Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting o...
1,418 Citations Source Cite
Published on Jan 1, 2008in Journal of Atherosclerosis and Thrombosis 3.04
Dmitri Sviridov36
Estimated H-index: 36
Nigora Mukhamedova15
Estimated H-index: 15
+ 2 AuthorsJaye Chin-Dusting28
Estimated H-index: 28
Plasma concentration of high density lipoprotein (HDL) is one of the most reliable negative risk factors for CVD. There is however convincing experimental and clinical evidence that plasma concentration of HDL does not convey the full picture of atheroprotective properties of HDL. HDL functionality, i.e. the ability of HDL to perform its many atheroprotective functions, is partly independent of HDL concentration and may be as important, if not more important, in determining the atheroprotective ...
85 Citations Source Cite
Published on Nov 1, 2009in Journal of the American College of Cardiology 16.83
John J.V. McMurray143
Estimated H-index: 143
(British Heart Foundation),
John Kjekshus73
Estimated H-index: 73
+ 11 AuthorsJohn Wikstrand61
Estimated H-index: 61
Objectives We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. Background Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transiti...
159 Citations Source Cite
Published on Dec 1, 2010in Biochimica et Biophysica Acta 3.44
Gordon A. Francis34
Estimated H-index: 34
Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with coronary artery disease risk in large epidemiologic studies. This rule, however, has many exceptions in individual patients, and evidence suggests that other facets of high-density lipoprotein particle biology not captured by measuring HDL-C levels are responsible for HDL's effects in vivo. This article reviews the evidence for the protective nature of HDL, current evidence from animal and human studies rega...
48 Citations Source Cite
Published on Dec 1, 2006in Clinics in Laboratory Medicine 1.90
Elias J. Jeyarajah10
Estimated H-index: 10
William C. Cromwell13
Estimated H-index: 13
(Wake Forest University),
James D. Otvos51
Estimated H-index: 51
Laboratory measurements of plasma lipids (principally cholesterol and triglycerides) and lipoprotein lipids (principally low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol) have been the cornerstone of the clinical assessment and management of atherosclerotic cardiovascular disease (CVD) risk since the Friedewald formula was introduced in 1972 for estimating LDL cholesterol [1]. The lipoprotein particles that carry cholesterol and triglycerides in the bloodstream are th...
432 Citations Source Cite
Published on Mar 1, 2006in Nature Reviews Cardiology 15.16
Anatol Kontush51
Estimated H-index: 51
(National Institutes of Health),
M. John Chapman68
Estimated H-index: 68
(National Institutes of Health)
Small, dense HDL possesses potent antioxidative activity but this is compromised under conditions of atherogenic dyslipidemia. The raising of HDL cholesterol levels might, however, improve functionality. In this review, Kontush and Chapman explore the mechanisms behind the antiatherogenic effects of small HDL, and the possible roles of these particles as therapeutic targets.
240 Citations Source Cite
Published on Mar 1, 2011in Journal of Clinical Lipidology 3.58
James D. Otvos51
Estimated H-index: 51
Samia Mora46
Estimated H-index: 46
(Brigham and Women's Hospital)
+ 3 AuthorsDavid C. Goff75
Estimated H-index: 75
(Wake Forest University)
Background The amount of cholesterol per low-density lipoprotein (LDL) particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals. Methods LDL-P measured by nuclear magnetic resonance spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atheroscl...
191 Citations Source Cite
Hong Feng7
Estimated H-index: 7
Xiang-An Li22
Estimated H-index: 22
Purpose of review To address the progress of the investigation on dysfunctional high-density lipoprotein (HDL).
33 Citations Source Cite
Published on Apr 1, 2009in Journal of Clinical Lipidology 3.58
Sunita Dodani3
Estimated H-index: 3
(University of Kansas),
Deanna G. Grice1
Estimated H-index: 1
(Georgia Regents University),
Sunil K. Joshi16
Estimated H-index: 16
(Georgia Regents University)
Abstract Over the past several decades, it has been clearly established that higher plasma concentrations of high-density lipoprotein (HDL) are related to lower risk of coronary artery disease (CAD). According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, the HDL level of
17 Citations Source Cite
  • References (39)
  • Citations (130)
Cited By130
Published on Feb 1, 2015in Journal of the American College of Cardiology 16.83
Qi Yue13
Estimated H-index: 13
(Capital Medical University),
Jie Fan3
Estimated H-index: 3
(Capital Medical University)
+ 8 AuthorsYan Li14
Estimated H-index: 14
(Capital Medical University)
Abstract Background Cholesterol-overloaded high-density lipoprotein (HDL) particles exert a negative impact on the antiatherogenic function of HDL in experimental studies. However, it remains unclear whether cholesterol-overloaded HDL particle is involved in the development of atherosclerosis in humans. Objectives The objective of this study was to explore whether cholesterol-overloaded HDL particles are associated with the progression of carotid atherosclerosis in a cardiovascular disease–free ...
32 Citations Source Cite
Published on Dec 1, 2015in American Journal of Cardiology 3.17
Jamal S. Rana19
Estimated H-index: 19
(University of California, San Francisco),
Jennifer Y. Liu24
Estimated H-index: 24
(University of California, San Francisco)
+ 4 AuthorsAndrew J. Karter5
Estimated H-index: 5
(University of California, San Francisco)
The risk of future coronary heart disease (CHD) in subjects with diabetes and "metabolic dyslipidemia" (high triglyceride [TGs] and low high-density cholesterol levels) remains a matter of concern. Little is known regarding the risk of CHD for this phenotype with low-density lipoprotein cholesterol (LDL-C) levels
11 Citations Source Cite
Published on Nov 1, 2015in Current Diabetes Reports 3.57
Leah E. Cahill19
Estimated H-index: 19
(Dalhousie University),
Monica L. Bertoia14
Estimated H-index: 14
(Harvard University)
+ 2 AuthorsMajken K. Jensen43
Estimated H-index: 43
(Harvard University)
Cardiovascular disease (CVD) is the most common cause of death and disability worldwide. Therefore, great importance has been placed on the discovery of novel risk factors and metabolic pathways relevant in the prevention and management of CVD. Such research is ongoing and may continue to lead to better risk stratification of individuals and/or the development of new intervention targets and treatment options. This review highlights emerging biomarkers related to lipid metabolism, glycemia, infl...
7 Citations Source Cite
Published on Dec 1, 2015in Atherosclerosis 4.47
Mark A. Sarzynski22
Estimated H-index: 22
(Pennington Biomedical Research Center),
Jeffrey H. Burton5
Estimated H-index: 5
(Pennington Biomedical Research Center)
+ 15 AuthorsCatherine R. Mikus14
Estimated H-index: 14
(Duke University)
Abstract Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, ...
23 Citations Source Cite
Published on Oct 5, 2015in Frontiers in Pharmacology 3.83
Anatol Kontush51
Estimated H-index: 51
(National Institutes of Health)
Previous studies indicate that reduced concentrations of circulating high-density lipoprotein (HDL) particles can be superior to HDL-cholesterol (HDL-C) levels as a predictor of cardiovascular disease. Measurements of HDL particle numbers, therefore, bear a potential for the improved assessment of cardiovascular risk. Furthermore, such measurement can be relevant for the evaluation of novel therapeutic approaches targeting HDL. Modern in-depth analyses of HDL particle profile may further improve...
34 Citations Source Cite
Published on Mar 1, 2013in Drugs 4.69
Joe M. Chehade3
Estimated H-index: 3
(University of Florida),
Margaret Gladysz2
Estimated H-index: 2
(University of Florida),
Arshag D. Mooradian50
Estimated H-index: 50
(University of Florida)
Dyslipidemia is one of the key risk factors for cardiovascular disease (CVD) in diabetes mellitus. Despite the mounting clinical trial data, the management of dyslipidemia other than lowering the low density lipoprotein cholesterol (LDL-c) continues to be controversial. The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration, reduced high density lipoprotein cholesterol (HDL-c) concentration, and increased concentration of small dense LDL particles. These ...
76 Citations Source Cite
Published on May 1, 2015in Current Cardiology Reports 1.96
Haider J. Warraich16
Estimated H-index: 16
(Harvard University),
Nathan D. Wong79
Estimated H-index: 79
(University of California, Irvine),
Jamal S. Rana19
Estimated H-index: 19
(University of California, San Francisco)
Individuals with type 2 diabetes mellitus have a high residual risk of cardiovascular disease (CVD) despite maximal statin therapy and lifestyle interventions. In addition, adults with diabetes frequently exhibit the pattern of elevated triglycerides, small dense LDL, and reduced levels of high density lipoprotein cholesterol (HDL), also known as diabetic dyslipidemia. The role of combination therapy with an additional agent such as niacin, ezetimibe, fenofibrate, and n-3 fatty acids have been e...
9 Citations Source Cite
Published on May 22, 2012in Circulation 18.88
Ira S. Ockene61
Estimated H-index: 61
(University of Massachusetts Medical School)
Current guidelines recommend the use of standard lipid measures, including the total to high-density lipoprotein cholesterol ratio, inexpensive and readily available, for routine cardiovascular disease risk assessment.1 Other studies and consensus panels, however, have suggested that the number of circulating atherogenic particles (and apoB as a surrogate) provide better risk prediction than standard lipid measures.2 Tests such as the Vertical Auto Profile (Atherotech, Birmingham, AL), which det...
1 Citations Source Cite
Published on Apr 1, 2014in Atherosclerosis 4.47
Paul T. Williams49
Estimated H-index: 49
(Lawrence Berkeley National Laboratory),
Xue Qiao Zhao33
Estimated H-index: 33
(University of Washington)
+ 3 AuthorsRonald M. Krauss107
Estimated H-index: 107
(Children's Hospital Oakland Research Institute)
Abstract Background Compare gradient gel electrophoresis (GGE), vertical auto profile ultracentrifugation (VAP-II), nuclear magnetic resonance spectroscopy (NMR), and ion mobility for their ability to relate low- (LDL), intermediate- (IDL), very-low-density (VLDL) and high-density lipoprotein (HDL) subfraction concentrations to atherosclerotic progression. Methods and results Regression analyses of 136 patients who received baseline and follow-up coronary angiographies and subfraction measuremen...
44 Citations Source Cite
Published on Aug 1, 2014in Clinical Biochemistry 2.58
Robin P. F. Dullaart43
Estimated H-index: 43
(University Medical Center Groningen),
James D. Otvos1
Estimated H-index: 1
Richard W. James30
Estimated H-index: 30
Abstract Objectives We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM). Design and methods Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-dia...
19 Citations Source Cite