Lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS)1-5. Its role in cardiovascular disease is strongly supported by a large body of clinical evidence encompassing observational studies, meta-analyses, genome wide association, and Mendelian randomization studies across multiple populations1. Elevated Lp(a) levels independently predict clinical events related to myocardial infarction, stroke, peripheral arterial disease, and aortic valve stenosis.

Statins are the cornerstone of lipid-lowering therapy (LLT) for the reduction of low-density lipoprotein cholesterol (LDLc) levels (1,2). A significant proportion of patients, especially those at high or very high cardiovascular risk, may need, and would eventually benefit from, high dose of statins or combination of LLTs (3,4). A metanalysis that included the first trials with high-doses of statins concluded that such intensive therapy effectively reduced non-fatal major adverse cardiovascular events (MACE) but had no effect on cardiovascular or all-cause mortality (5).

The relationships between intake and tissue levels of saturated fatty acids (SFAs) and cardiovascular disease (CVD) risk have been extensively studied over the past six decades. Individual SFAs differ in their metabolic effects. Palmitic acid (C16:0), a long chain fatty acid (FA), is the most abundant SFA in the U.S. diet representing about 55% of dietary SFAs1, and comprises about 20-30% of all FA in membrane phospholipids (PL) and triglycerides (TG)2. Palmitic acid is derived from the diet or by endogenous synthesis (i.e., de novo lipogenesis (DNL)) from excess energy intake from carbohydrates and/or protein.