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Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study.

ABSTRACT: The prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients.A total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n?=?3966) or the diet plus pravastatin (n?=?3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C).CHD incidence was lower in patients with HDL-C >60-90 mg/dL (-52%, p = 0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C ? 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60-90 mg/dL than in those with HDL-C ? 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60-90 mg/dL.Patients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events.Clinical trials.gov NCT00211705.

SUBMITTER: Nakamura H

PROVIDER: S-EPMC4246450 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study.

Nakamura Haruo H Mizuno Kyoichi K

Lipids in health and disease 20140818

<h4>Background</h4>The prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients.<h4>Methods</h4>A total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n = 3966) or the diet plus pravas ...[more]

PMID: 25135178

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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.

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Project description:Background and aimsPeripheral artery disease (PAD) is a systemic manifestation of atherosclerosis that is associated with a high risk of major adverse cardiovascular events (MACE). LDL aggregation contributes to atherosclerotic plaque progression and may contribute to plaque instability. We aimed to determine if LDL aggregation is associated with MACE in patients with PAD undergoing lower extremity revascularization (LER).MethodsTwo hundred thirty-nine patients with PAD undergoing LER had blood collected at baseline and were followed prospectively for MACE (myocardial infarction, stroke, cardiovascular death) for one year. Nineteen age, sex and LDL-C-matched control subjects without cardiovascular disease also had blood drawn. Subject LDL was exposed to sphingomyelinase and LDL aggregate size measured via dynamic light scattering.ResultsMean age was 72.3 ± 10.9 years, 32.6% were female, and LDL-cholesterol was 68 ± 25 mg/dL. LDL aggregation was inversely associated with triglycerides, but not associated with demographics, LDL-cholesterol or other risk factors. Maximal LDL aggregation occurred significantly earlier in subjects with PAD than in control subjects. 15.9% of subjects experienced MACE over one year. The 1st tertile (shortest time to maximal aggregation) exhibited significantly higher MACE (25% vs. 12.5% in tertile 2 and 10.1% in tertile 3, p = 0.012). After multivariable adjustment for demographics and CVD risk factors, the hazard ratio for MACE in the 1st tertile was 4.57 (95% CI 1.60-13.01; p = 0.004) compared to tertile 3. Inclusion of LDL aggregation in the Framingham Heart Study risk calculator for recurrent coronary heart disease events improved the c-index from 0.57 to 0.63 (p = 0.01).ConclusionsWe show that in the setting of very well controlled LDL-cholesterol, patients with PAD with the most rapid LDL aggregation had a significantly elevated MACE risk following LER even after multivariable adjustment. This measure further improved the classification specificity of an established risk prediction tool. Our findings support broader investigation of this assay for risk stratification in patients with atherosclerotic CVD.

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Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study.

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Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study.

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