Clinical guideline evidence matters. Recent 2018 American Heart Association/American College of Cardiology/Multisociety guidelines present strong evidence to support maximally tolerated statin therapy as a first step in patients aged 20 to 75 years with primary severe elevations of low-density lipoprotein cholesterol (LDL-C) of 190 mg/dL (to convert to millimoles per liter, multiply by 0.0259) or greater.1 This cutoff identifies a high-risk group that includes individuals with heterozygous familial hypercholesterolemia (heFH) with autosomal codominance inheritance, physical signs such as arcus and tendon xanthomas in up to 50%, heterozygous variant in low-density lipoprotein receptors, apolipoprotein, PCSK9 genes, and a greater than 20-fold increase in atherosclerotic cardiovascular disease (ASCVD).1,2 This is contrasted with a phenotypically severe hypercholesterolemia, where inheritance may be polygenic and physical examination findings are usually lacking, but still associated with a greater than 5-fold increase in ASCVD.2