Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is a well-established mediator of atherosclerosis and a key target for intervention for the primary and secondary prevention of ASCVD. However, despite substantial reduction in LDL-C, patients continue to have recurrent ASCVD events. Hypertriglyceridemia may be an important contributor of this residual risk. Observational and genetic epidemiological data strongly support a causal role of triglycerides (TGs) and the cholesterol content within triglyceride-rich lipoproteins (TGRLs) and/or remnant cholesterol (RC) in the development of ASCVD. TGRLs are composed of hepatically derived very low-density lipoprotein and intestinally derived chylomicrons. RC is the cholesterol content of all TGRLs and plasma TGs serve as a surrogate measure of TGRLs and RC. Although lifestyle modification remains the cornerstone for management of hypertriglyceridemia, many novel drugs are in development and have shown impressive efficacy in lowering TG levels. Several ongoing, randomized controlled trials are underway to examine the impact of these novel agents on ASCVD outcomes. In this comprehensive review, we provide an overview of the biology, epidemiology, and genetics of TGs and ASCVD; we discuss current and novel TG-lowering therapies under development.

Coo Coo: Charles Darwin was fascinated by the domestic rock pigeon and used this dramatic example of diversity within a species to communicate his ideas about natural selection. Many derived traits in domestic pigeons converge on ecologically and evolutionarily relevant traits in wild species. Shapiro et al. (p. 1063 , published online 31 January; see the cover) sequenced the genome of the domestic rock pigeon ( Columba livia ), along with those of 36 breeds and two feral accessions and its sister species, the hill pigeon ( C. rupestris ). The results reveal the underlying genetics of the head crest and suggest that all crested breeds may have originated from a single mutational event.

Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease. A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200–500 mg/dL (2.26–5.65 mmol/L). Patients received olezarsen (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6–12 months. The primary endpoint was the percent change in fasting triglyceride levels from baseline to Month 6 of exposure. Baseline median (interquartile range) fasting triglyceride levels were 262 (222–329) mg/dL [2.96 (2.51–3.71) mmol/L]. Treatment with olezarsen resulted in mean percent triglyceride reductions of 23% with 10 mg every 4 weeks, 56% with 15 mg every 2 weeks, 60% with 10 mg every week, and 60% with 50 mg every 4 weeks, compared with increase by 6% for the pooled placebo group (P-values ranged from 0.0042 to 10.0 mmol/L primarily pancreatitis risk in patients with familial chylomicronemia syndrome and multifactorial chylomicronemia syndrome (represented by milky plasma). Treatment with olezarsen with the planned Phase 3 doses of 50 and 80 mg subcutaneously monthly would be expected to substantially reduce triglyceride levels in the entire continuum of hypertriglyceridaemia.

Purpose of Review: Sleep is an important component of cardiovascular (CV) health. This review summarizes the complex relationship between sleep and CV disease (CVD). Additionally, we describe the data supporting the treatment of sleep disturbances in preventing and treating CVD. Recent Findings: Recent guidelines recommend screening for obstructive sleep apnea in patients with atrial fibrillation. New data continues to demonstrate the importance of sleep quality and duration for CV health. Summary: There is a complex bidirectional relationship between sleep health and CVD. Sleep disturbances have systemic effects that contribute to the development of CVD, including hypertension, coronary artery disease, heart failure, and arrhythmias. Additionally, CVD contributes to the development of sleep disturbances. However, more data are needed to support the role of screening for and treatment of sleep disorders for the prevention of CVD.