Introduction: Cardiovascular (CV) disease remains a leading cause of mortality despite statin therapy. Statin add-on lipid-lowering therapies have been investigated for CV risk reduction, but their effect on CV mortality has not been reviewed.
Methods: This review describes CV outcomes trials of add-on therapies to statins, highlighting findings related to the primary composite CV endpoints and the more patient-centric endpoint of CV-related mortality.
Introduction: Long-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE.
View Article and Find Full Text PDFNone of the clinical trials of omega-3 fatty acids using combinations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were able to show any effect on cardiovascular outcomes, despite reductions in triglyceride levels. In contrast, the Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT), which employed high-dose (4 g) purified EPA, demonstrated a 25% reduction in atherosclerotic cardiovascular disease-related events compared with placebo (hazard ratio 0.75; 95% confidence interval 0.
View Article and Find Full Text PDFBackground: Fatty acids (FA) play an important role in health and heart disease risk.
Objective: We evaluated relationships of plasma FA levels, especially omega-3 FA, with sex, age, and reported heart disease mortality rates by state in a very large clinical population.
Methods: Plasma FA were measured by gas chromatography/mass spectrometry after lipid extraction in 1,169,621 fasting United States subjects grouped according to sex (56.
Treatment with icosapent ethyl 4 g/day, a highly purified and stable ethyl ester of eicosapentaenoic acid (EPA), demonstrated a significant reduction in atherosclerotic cardiovascular disease (ASCVD) events and death in REDUCE-IT. However, analyses of REDUCE-IT and meta-analyses have suggested that this clinical benefit is greater than can be achieved by triglyceride reduction alone. EPA therefore may have additional pleiotropic effects, including anti-inflammatory and anti-aggregatory mechanisms.
View Article and Find Full Text PDFSingle-molecule and single-cell analysis techniques have opened new opportunities for characterizing and analyzing heterogeneity within biological samples. These detection methods are often referred to as digital assays because the biological sample is partitioned into many small compartments and each compartment contains a discrete number of targets (e.g.
View Article and Find Full Text PDFAims: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients.
View Article and Find Full Text PDFThe high-purity eicosapentaenoic acid (EPA) prescription fish oil-derived omega-3 fatty acid (omega-3), icosapent ethyl (IPE), was recently approved by the United States Food and Drug Administration (FDA) for cardiovascular disease (CVD) prevention in high-risk patients. This approval is based on the 25% CVD event risk reduction observed with IPE in the pre-specified primary composite endpoint (cardiovascular [CV] death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) in the landmark Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT). Notably, this reduction in CVD event risk with IPE was an incremental benefit to well-controlled low-density lipoprotein cholesterol; patients in REDUCE-IT had elevated triglyceride (TG) levels (135-499 mg/dL) and either had a history of atherosclerotic CVD or diabetes with additional CV risk factors.
View Article and Find Full Text PDFBackground And Aims: Dyslipidemia with elevated triglycerides (TGL) and low high-density lipoprotein cholesterol (HDL-C) predicts residual cardiovascular risk, despite goal LDL-C levels and optimal statin therapy. Coronary plaque characterization by CCTA can provide mechanistic understanding of coronary artery disease and associated prognosis. The role of HDL-C in the pathogenesis of atherosclerosis is not well understood in statin-treated patients with elevated TGL.
View Article and Find Full Text PDFAims: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients.
View Article and Find Full Text PDFBackground: Elevated postprandial triglycerides reflect a proatherogenic milieu, but underlying mechanisms are unclear.
Objective: We examined differences between fasting and nonfasting profiles of directly measured lipoprotein size and subfractions to assess if postprandial triglycerides reflected increases in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and remnants, or small dense lipid depleted LDL (sdLDL) particles.
Methods: We conducted a cross-sectional analysis of 15,397 participants (10,135 fasting; 5262 nonfasting [<8 hours since last meal]) from the VITamin D and OmegA-3 TriaL.
The ability to measure mutations in plasma cell-free DNA (cfDNA) has the potential to revolutionize cancer surveillance and treatment by enabling longitudinal monitoring not possible with solid tumor biopsies. However, obtaining sufficient quantities of cfDNA remains a challenge for assay development and clinical translation; consequently, large volumes of venous blood are typically required. Here, we test proof-of-concept for using smaller volumes via fingerstick collection.
View Article and Find Full Text PDFDespite reducing progression and promoting regression of coronary atherosclerosis, statin therapy does not fully address residual cardiovascular (CV) risk. High-purity eicosapentaenoic acid (EPA) added to a statin has been shown to reduce CV events and induce regression of coronary atherosclerosis in imaging studies; however, data are from Japanese populations without high triglyceride (TG) levels and baseline EPA serum levels greater than those in North American populations. Icosapent ethyl is a high-purity prescription EPA ethyl ester approved at 4 g/d as an adjunct to diet to reduce TG levels in adults with TG levels >499 mg/dL.
View Article and Find Full Text PDFResidual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk.
View Article and Find Full Text PDFWe present a mesodissection platform that retains the advantages of laser-based dissection instrumentation with the speed and ease of manual dissection. Tissue dissection in clinical laboratories is often performed by manually scraping a physician-selected region from standard glass slide mounts. In this manner, costs associated with dissection remain low, but spatial resolution is compromised.
View Article and Find Full Text PDFObjective: Given the substantial economic and health burden of cardiovascular disease and the residual cardiovascular risk that remains despite statin therapy, adjunctive therapies are needed. The purpose of this model was to estimate the cost-effectiveness of high-purity prescription eicosapentaenoic acid (EPA) omega-3 fatty acid intervention in secondary prevention of cardiovascular diseases in statin-treated patient populations extrapolated to the US.
Methods: The deterministic model utilized inputs for cardiovascular events, costs, and utilities from published sources.
Background/objectives: Epidemiological, diet-based, and some interventional outcomes studies suggest that polyunsaturated omega-3 fatty acids (OM3FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), confer cardiovascular protection in some patient populations. This review examines the historical context of OM3FAs in cardiovascular disease and future perspectives on the place of OM3FA products in reducing cardiovascular risk.
Methods: Relevant articles were identified via PubMed/Medline and Google Scholar searches through 2015 and through reference lists of selected publications.
Background: Dyslipidemia plays a significant role in the progression of cardiovascular disease. The apolipoprotein (apo) A1 remnant ratio (apo A1/VLDL3-C + IDL-C) has recently been shown to be a strong predictor of death/myocardial infarction risk among women >50 years undergoing angiography. However, whether this ratio is associated with coronary heart disease risk among other populations is unknown.
View Article and Find Full Text PDFResidual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture.
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