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Lowering low-density lipoprotein cholesterol (LDL-C) is the primary lipid target to prevent atherosclerotic cardiovascular disease (ASCVD) . Yet even at very low LDL-C levels, high-risk patients continue to experience cardiovascular events .
In the search for possible lipid contributors to this high residual cardiovascular risk, attention focuses on atherogenic dyslipidemia, the combination of low plasma concentration of high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides.
The ‘HDL hypothesis’, which proposed that HDL-C could be protective against ASCVD has been largely abandoned after trials testing numerous HDL-C raising strategies, against a background of best evidence-based medicine including statins, failed to show cardiovascular benefit.
The stage is now set for reconsideration of triglyceride-rich lipoproteins as a causal cardiovascular risk factor . Since 2007, there has been renewed interest in elevated plasma triglycerides, a surrogate for triglyceride-rich lipoproteins and their remnants . This sea-change in thinking has been driven by new genetic insights showing that triglyceride-rich lipoproteins are implicated in the causal pathway for ASCVD . Accumulating epidemiologic evidence also supports an association between triglyceride-rich lipoproteins and ASCVD risk.
The critical test is whether lowering elevated levels of triglycerides reduces residual cardiovascular risk . The PROMINENT trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabetes) is a critical test of the hypothesis that lowering elevated triglycerides with the novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) pemafibrate, will reduce the high residual cardiovascular risk in type 2 diabetes patients (with and without ASCVD) on intensive statin therapy.
This booklet created by professors Børge G. Nordestgaard, Michel P. Hermans, and Jean-Charles Fruchart provides a critical background to triglyceride-rich lipoproteins and their role in ASCVD, concluding with discussion of the trials – past and present – that have targeted elevated triglycerides to lower residual cardiovascular risk.