Triglycerides: Mendelian Randomization Studies Suggest Causal Role, but How to Treat in 2019?

AbstractPurpose of ReviewHypertriglyceridemia (HTG), defined by fasting levels at or exceeding 200  mg/dL, is characterized as a pro-inflammatory, pro-thrombotic, metabolic state associated with endothelial dysfunction, insulin resistance, type 2 diabetes mellitus (T2DM), and increased risk of cardiovascular disease (CVD). Mendelian randomization studies now support a causal role for TG-rich lip oproteins in CVD risk enhancement. Yet, until recently, only post-hoc analyses from clinical trials suggested that treating HTG would translate into reduced CVD risk.Recent FindingsThe results of Reduction of Cardiovascular Events with Icosapent Ethyl –Intervention Trial demonstrated for the first time that patients with HTG and elevated CVD risk (i.e., pre-existing CVD or DM with additional risk factors) benefited after treatment with icosapent ethyl (IPE), a highly purified eicosapentanoic acid (EPA) taken 4 g daily. Ironically, the TG-lower ing effect of IPE was relatively modest (20%), suggesting the interplay of other mechanisms beyond TG lowering that contributed to the robust benefits observed (25% relative risk reduction in the primary CVD endpoint). These mechanisms include downregulation of pro-inflammatory signaling pathways an d restoration of endothelial dysfunction, cellular processes that are aggravated in HTG states. Consequently, high-risk patients with HTG should be considered for IPE therapy beyond traditional measures outlined in the 2018 American Heart Associa...
Source: Current Cardiovascular Risk Reports - Category: Cardiology Source Type: research