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Treating Severe Hypercholesterolemia—If Not Now, When?
JAMA Cardiology  (IF14.676),  Pub Date : 2021-11-15, DOI: 10.1001/jamacardio.2021.4987
Neil J. Stone

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

For those with heFH, low-cost statins have been shown to be effective and safe with the potential to reduce mortality and even produce cost savings.3 In an informative Dutch multicenter cohort experience,4 introduction of statins markedly improved the coronary heart disease–free survival rate of heFH in men and women who were seen without statin treatment.4

Yet despite clear evidence for benefit from identifying and treating this high-risk condition, a high proportion of patients who qualify for statin therapy do not receive it. Al-Kindi et al5 used a deidentified, cloud-based US clinical registry that included data from inpatient and outpatient encounters from 360 medical centers in all 50 states to indicate how infrequently guidance regarding statin treatment of LDL-C levels of 190 mg/dL or greater is heeded. They found prescription rates of only 66% for those with documented LDL-C of 190 mg/dL or greater and no associated ASCVD. For young adults, the news was even more grim. Less than half (45%) of participants younger than 40 years were receiving a statin. In this issue of JAMA Cardiology, Newton et al6 extend these somber observations. They used data from a large health care system including academic and community-level practices in the northeastern US. The findings were striking. Fewer than 1 in 3 young adults with severe hypercholesterolemia of 190 mg/dL or greater achieved the guideline-directed LDL-C reduction of 50% or more. Moreover, nearly 1 in 4 patients persistently had LDL-C levels of 190 mg/dL or greater after 8 years of follow-up.