Lipid Screening in Childhood for Detection of Familial Hypercholesterolemia

Study Questions:

What is the evidence on benefits and harms of screening adolescents and children for heterozygous familial hypercholesterolemia (FH)?


At the request of the US Preventive Services Task Force (USPSTF), a systematic review of studies published between January 1, 2005, and June 2, 2015 was conducted, which included a previous USPSTF report. Study selection criteria included fair- and good-quality studies in English with participants 0-20 years of age. Results were qualitatively summarized.


Based on two studies (n = 83,241), the diagnostic yield of universal screening for FH in childhood was 1.3 to 4.8 cases per 1,000 screened, with no evidence of harm. Eight placebo trials of statins (n = 1,071, 6-104 weeks) found low-density lipoprotein cholesterol (LDL-C) decreases of 20-40%; one trial (n = 214) showed a 2.01% decrease in carotid intima-media thickness with statins, compared with 1.02% with placebo (p = 0.02). Three placebo trials of bile acid–sequestrants (n = 332, 8-52 weeks) showed LDL-C reductions of 10-20%. In a 33-week trial in 248 subjects, ezetimibe with simvastatin resulted in greater LDL-C reductions compared with simvastatin alone (mean, −54.0% [standard deviation, 1.4%] vs. −38.1% [standard deviation, 1.4%]). Ezetimibe monotherapy (n = 138) showed mean LDL-C decreases of 28% (95% confidence interval, −31% to −25%) from baseline and negligible change with placebo at 12 weeks. Eighteen studies found statins generally well tolerated. One observational study found lower, but still normal, DHEA sulfate concentrations in statin-treated men with FH at 10-year follow-up. There was no eligible evidence on the effect of FH treatment on myocardial infarction or stroke in adulthood.


Screening can detect FH in children, and lipid-lowering treatment in childhood can reduce lipid concentrations in the short term, with little evidence of harm. There is no evidence for the effect of screening for FH in childhood on lipid concentrations or cardiovascular outcomes in adulthood, or on the long-term benefits or harms of beginning lipid-lowering treatment in childhood.


The evidence that having a life-long elevated LDL-C is associated with atherosclerosis beginning in childhood and increases the risk of cardiovascular events and mortality is overwhelming. Simon Broome Registry of Heterozygous FH found excess coronary heart disease mortality compared with the general population, with extremely elevated standardized mortality ratios, particularly in the group aged 20-39 years. This was published 25 years ago. The Europeans have been much more aggressive in screening for, defining, and detecting and treating heterozygous FH. And they have found that the classic definitions using LDL-C levels underestimate the incidence. What are we waiting for?

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