[Are triglyceride rich lipoproteins more dangerous than LDL cholesterol?].

Two prospective epidemiological studies have pointed to the importance of triglyceride rich lipoproteins in causing atherosclerosis. Lipoprotein analyses show that it is the cholesterol content of the lipoproteins that relates to atherosclerotic cardiovascular disease. As high blood levels of these lipoproteins are mostly seen in obese people changes in lifestyle seem to be the most relevant therapeutic measure.

[Prevention of cardiovascular disease needs longer-term perspective].

Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. A simple tool has been provided for assessment of individual long-term risk and the potential benefit of early lipid-lowering intervention.

Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease.

Objective: Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome.

Association of high-density lipoprotein particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial.

Background: High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS).

Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial.

Background: Data on PCSK9 inhibition in chronic kidney disease (CKD) is limited.

Objectives: The purpose of this study was to compare outcomes with evolocumab and placebo according to kidney function.

Methods: The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized individuals with clinically evident atherosclerosis and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl or non-high-density lipoprotein cholesterol ≥100 mg/dl to evolocumab or placebo.

Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials.

Background: Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain.

Methods: Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures.

Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.

Importance: It is uncertain whether lipoprotein(a) [Lp(a)], which is associated with incident cardiovascular disease, is an independent risk factor for recurrent cardiovascular events after acute coronary syndrome (ACS).

Objective: To determine the association of Lp(a) concentration measured after ACS with the subsequent risk of ischemic cardiovascular events.

Design, Setting, And Participants: This nested case-cohort analysis was performed as an ad hoc analysis of the dal-Outcomes randomized clinical trial.

Early, intensive statin treatment reduces 'hard' cardiovascular outcomes after acute coronary syndrome.

Background Early, intensive statin treatment is the standard of care after acute coronary syndrome (ACS). However, the benefit of this approach to prevent major adverse cardiovascular events has been demonstrated in only one randomised, placebo controlled trial. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial demonstrated that atorvastatin 80 mg daily, compared with placebo, reduced time to first occurrence of death, non-fatal myocardial infarction, resuscitated cardiac arrest, or hospitalisation for unstable angina (stroke not included) during the 16 week period following ACS.

Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure.

Background: Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF.

Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation: Concordance With Clinical Outcomes.

Background: Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation.

Methods And Results: Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care.

Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins.

Background: Most patients with acute coronary syndrome (ACS) are treated with statins, which reduce atherogenic triglyceride-rich lipoproteins. It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment.

Objectives: This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins.

Treat-to-target versus dose-adapted statin treatment of cholesterol to reduce cardiovascular risk.

Clinical guidelines should be based on the best available evidence and are of great importance for patient care and disease prevention. In this respect, the 2013 American College of Cardiology/American Heart Association report is highly appreciated and well-recognized. The report included critical questions concerning hypercholesterolaemia, but its translation into a clinical guideline initiated intense debate worldwide because of the recommendation to switch from a treat-to-target approach for low-density-lipoprotein-cholesterol to a statin dose-based strategy.

Pharmacogenomic determinants of the cardiovascular effects of dalcetrapib.

Background: Dalcetrapib did not improve clinical outcomes, despite increasing high-density lipoprotein cholesterol by 30%. These results differ from other evidence supporting high-density lipoprotein as a therapeutic target. Responses to dalcetrapib may vary according to patients' genetic profile.

PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.

Background: Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol, increased plasma LDL cholesterol concentrations, and premature cardiovascular disease. Despite intensive statin therapy, with or without ezetimibe, many patients are unable to achieve recommended target levels of LDL cholesterol. We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder.

Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome.

Background: Liver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia.

Methods: We performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200 μg day(-1) eprotirome or placebo for 12 weeks.

Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study.

Background: Eprotirome is a liver-selective thyroid hormone receptor agonist that has been shown to lower plasma LDL cholesterol concentrations in previous phase 1 and 2 studies of patients with dyslipidaemia. We aimed to assess the long-term safety and efficacy of 50 μg and 100 μg eprotirome in patients with familial hypercholesterolaemia.

Methods: For this randomised, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial, we enrolled patients between Oct 3, 2011, and Feb 14, 2012, at 53 sites in 11 countries in Europe, Africa, and south Asia.

Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-to-moderate baseline elevations in alanine aminotransferase levels.

Background: Statins may reduce cardiovascular (CV) morbidity in patients with mild-to-moderate elevations in liver enzyme levels. This post-hoc analysis of the IDEAL study compared intensive versus moderate statin therapy for the prevention of CV events in coronary heart disease patients with normal and elevated baseline levels of serum alanine aminotransferase (ALT).

Methods: Cox regression analysis was used to investigate the effect of atorvastatin 80 mg/day versus simvastatin 20-40 mg/day on the risk of IDEAL study end points in patients with normal baseline ALT (defined as ALT < ULN [upper limit of normal]) versus elevated baseline ALT (ALT ≥ ULN).

Inflammatory biomarkers, death, and recurrent nonfatal coronary events after an acute coronary syndrome in the MIRACL study.

Background: In acute coronary syndromes, C-reactive protein (CRP) strongly relates to subsequent death, but surprisingly not to recurrent myocardial infarction. Other biomarkers may reflect different processes related to these outcomes. We assessed 8 inflammatory and vascular biomarkers and the risk of death and recurrent nonfatal cardiovascular events in the 16 weeks after an acute coronary syndrome.

Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial.

Context: An estimated 10% to 20% of patients cannot tolerate statins or adequate doses to achieve treatment goals. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, promoting their degradation and increasing LDL cholesterol levels. In phase 1 studies, a human monoclonal antibody to PCSK9, AMG145, was well tolerated and reduced LDL cholesterol levels.