Dataset Information

Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes).

ABSTRACT: This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial.During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)-lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone.Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (? 150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization.CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (? 198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group.Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C-lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289).

SUBMITTER: Guyton JR

PROVIDER: S-EPMC3862446 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes).

Guyton John R JR Slee April E AE Anderson Todd T Fleg Jerome L JL Goldberg Ronald B RB Kashyap Moti L ML Marcovina Santica M SM Nash Stephen D SD O'Brien Kevin D KD Weintraub William S WS Xu Ping P Zhao Xue-Qiao XQ Boden William E WE

Journal of the American College of Cardiology 20130731 17

<h4>Objectives</h4>This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial.<h4>Background</h4>During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprot ...[more]

PMID: 23916935

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Project description:In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN.This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk.There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063).Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk.http://www.clinicaltrials.gov. Unique identifier: NCT00120289.

Project description:It is unclear whether high-density lipoprotein (HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort.We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years.In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis (hazard ratio, 1.08; 95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile (hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes.Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).

Project description:Background The American Heart Association recognizes high triglycerides as a cardiovascular risk factor. Methods and Results This retrospective observational administrative claims analysis (Optum Research Database) included statin-treated patients ?45 years old with diabetes mellitus and/or atherosclerotic cardiovascular disease, triglycerides 2.26 to 5.64 mmol/L, and a propensity-matched comparator cohort with triglycerides <1.69 mmol/L and high-density lipoprotein cholesterol >1.04 mmol/L. In the high-triglycerides cohort versus comparators (both n=10 990, 49% women), mean age was 61.7 versus 62.2 years and follow-up was 41.3 versus 42.1 months, respectively. Multivariate analysis of composite major cardiovascular events demonstrated significantly increased risk in the high-triglycerides (n=13 411 patients) versus comparator (n=32 506 patients) cohorts (hazard ratio [ HR ], 1.35; 95% confidence interval [ CI ], 1.225-1.485; P<0.001), with significantly higher risk for nonfatal myocardial infarction ( HR , 1.35; 95% CI , 1.19-1.52; P<0.001), nonfatal stroke ( HR , 1.27; 95% CI , 1.14-1.42; P<0.001), and need for coronary revascularization ( HR , 1.51; 95% CI , 1.34-1.69; P<0.001), but not unstable angina or cardiovascular death. Increased cardiovascular risk in the high-triglycerides versus comparator cohort was maintained, even with addition of non-high-density lipoprotein cholesterol to the multivariate model and when analyzing high and low high-density lipoprotein cholesterol subgroups. Average total healthcare cost per patient per month (cost ratio, 1.15; 95% CI , 1.084-1.210; P<0.001) and rate of occurrence of inpatient hospital stay ( HR , 1.17; 95% CI , 1.113-1.223; P<0.001) were also significantly greater in the high-triglycerides cohort. Conclusions In this real-world analysis, patients with high cardiovascular risk and high triglycerides had worse composite cardiovascular and health economic outcomes than patients with well-managed triglycerides and high-density lipoprotein cholesterol >1.04 mmol/L.

Project description:BACKGROUND:The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD). OBJECTIVES:To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality. METHODS:GlycA and very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle subclasses were quantified by nuclear magnetic resonance spectroscopy using available stored baseline (n = 2754) and 1-year in-trial (n = 2581) samples. Associations with CVD events and all-cause mortality were assessed using multivariable Cox proportional hazards regression adjusted for age, sex, diabetes, treatment assignment, and lipoproteins. RESULTS:Compared to placebo, ERN treatment lowered very low-density lipoprotein and LDL and increased HDL particle concentrations, increased LDL and HDL particle sizes (all P < .0001), but did not affect GlycA. Baseline and in-trial GlycA levels were associated with increased risk of CVD events: hazard ratio (HR) per SD increment, 1.17 (95% confidence interval [CI], 1.06-1.28) and 1.13 (1.02-1.26), respectively. However, none of the lipoprotein particle classes or subclasses was associated with incident CVD. By contrast, all-cause mortality was significantly associated with both GlycA (baseline HR: 1.46 [1.22-1.75]; in-trial HR: 1.41 [1.24-1.60]) and low levels of small HDL particles (baseline HR: 0.69 [0.56-0.86]; in-trial HR: 0.69 [0.56-0.86]). CONCLUSIONS:This Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial post hoc substudy indicates that inflammation, as indexed by GlycA, is unaffected by ERN treatment but is significantly associated with the residual risk of CVD and death in patients treated to low levels of LDL cholesterol.

Project description:BACKGROUND AND OBJECTIVES:Triglyceride-rich lipoproteins may contribute to the high cardiovascular risk of patients with CKD. This study evaluated associations of apo-B and markers of triglyceride-rich lipoproteins with cardiovascular events in people with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Analyses were conducted in 9270 participants with CKD in the Study of Heart and Renal Protection (SHARP): 6245 not on dialysis (mean eGFR 26.5 ml/min per 1.73 m2), and 3025 on dialysis when recruited. Cox regression methods were used to evaluate associations of lipids with incident atherosclerotic and nonatherosclerotic vascular events, adjusting for demographics and clinical characteristics. Hazard ratios (HRs) were calculated per 1 SD higher level for apo-B, HDL cholesterol, LDL cholesterol, triglyceride-rich lipoprotein cholesterol (i.e., total cholesterol minus LDL cholesterol minus HDL cholesterol), non-HDL cholesterol, log triglyceride, and log ratio of triglyceride to HDL cholesterol. RESULTS:During a median follow-up of 4.9 years (interquartile range, 4.0-5.5 years), 1406 participants experienced at least one atherosclerotic vascular event. In multivariable adjusted models, positive associations with atherosclerotic vascular events were observed for apo-B (HR per 1 SD, 1.19; 95% confidence interval, 1.12 to 1.27), triglycerides (1.06; 1.00 to 1.13), the ratio of triglyceride to HDL cholesterol (1.10; 1.03 to 1.18), and triglyceride-rich lipoprotein cholesterol (1.14; 1.05 to 1.25). By contrast, inverse associations with nonatherosclerotic vascular events were observed for each of these lipid markers: apo-B (HR per 1 SD, 0.92; 0.85 to 0.98), triglycerides (0.86; 0.81 to 0.92), the ratio of triglyceride to HDL cholesterol (0.88; 0.82 to 0.94), and triglyceride-rich lipoprotein cholesterol (0.85; 0.77 to 0.94). CONCLUSIONS:Higher apo-B, triglycerides, ratio of triglyceride to HDL cholesterol, and triglyceride-rich lipoprotein cholesterol concentrations were associated with increased risk of atherosclerotic vascular events in CKD. Reducing triglyceride-rich lipoproteins using novel therapeutic agents could potentially lower the risk of atherosclerotic cardiovascular disease risk in the CKD population.

Dataset Information

Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes).

Publications

Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes).

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