Understanding hypertriglyceridemia in women: clinical impact and management with prescription omega-3-acid ethyl esters

Thomas D DayspringNorth Jersey Institute of Menopausal Lipidology, Wayne, NJ, USABackground: Elevated triglycerides (TGs) are a common lipid disorder in the US and are associated with comorbidities such as pancreatitis, obesity, type 2 diabetes, and metabolic syndrome. TGs are generally elevated in postmenopausal women compared with premenopausal women. Meta-analysis has shown that elevated TGs are associated with an increased risk of coronary heart disease (CHD).Objective: This article provides a general overview of TG metabolism and reviews data on the epidemiology and risk of elevated TGs in women, as pregnancy and menopause, in particular, have been associated with unfavorable changes in the lipoprotein profile, including elevations in TGs. In addition, this review seeks to explain the recommended TG goals and treatment options for hypertriglyceridemia with an emphasis on severe hypertriglyceridemia (TGs ≥ 500 mg/dL) and its respective treatment with prescription omega-3-acid ethyl esters (P-OM3).Methods: MedLine was searched for articles published through August 2009 using the terms “hypertriglyceridemia” and “dyslipidemia”, with subheadings for “prevalence”, “women”, “treatment”, “guidelines”, “risk”, and “omega-3 fatty acids”. Publications discussing the epidemiology of hypertriglyceridemia, CHD risk, treatment guidelines for lipid management, or clinical trials involving P-OM3 were selected for review. The reference lists of relevant articles were also examined for additional citations.Results: Hypertriglyceridemia is associated with increased CHD risk. Women, especially those with polycystic ovarian syndrome, type 2 diabetes, or who are postmenopausal, should be monitored regularly for the impact of hypertriglyceridemia on their lipid profile. Cardiovascular risk of TGs can be indirectly assessed by monitoring non-high-density lipoprotein cholesterol (non-HDL-C) levels. There are multiple sets of guidelines providing recommendations for desirable low-density lipoprotein cholesterol, TG, and non-HDL-C levels. Treatment of hypertriglyceridemia includes lifestyle interventions and, if needed, pharmacologic therapy. In patients with severe hypertriglyceridemia, P-OM3 can reduce TGs by up to 45%.Conclusion: Physicians should regularly monitor the lipid profile of their female patients. Any lipid abnormality should be managed promptly according to established guidelines. P-OM3 provide a well-tolerated option for the treatment of severe hypertriglyceridemia.Keywords: triglycerides, Lovaza, P-OM3, women, lipids, omega-

Ezetimibe therapy: mechanism of action and clinical update.

The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Although statin therapy is the mainstay for LDL-C lowering, a significant percentage of patients prescribed these agents either do not achieve targets with statin therapy alone or have partial or complete intolerance to them. For such patients, the use of adjuvant therapy capable of providing incremental LDL-C reduction is advised. One such agent is ezetimibe, a cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border. Its primary target of action is the cholesterol transport protein Nieman Pick C1 like 1 protein. Ezetimibe is an effective LDL-C lowering agent and is safe and well tolerated. In response to significant controversy surrounding the use and therapeutic effectiveness of this drug, we provide an update on the biochemical mechanism of action for ezetimibe, its safety and efficacy, as well as the results of recent randomized studies that support its use in a variety of clinical scenarios

Data_Sheet_1_Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development.docx

IntroductionWe sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion.MethodsWe analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers.ResultsMost highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis.DiscussionTriglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development.Clinical trial registrationGLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].</p