Familial hypercholesterolemia is a genetic disorder affecting 0.2 percent or more of many populations. It leads to impaired low-density lipoprotein (LDL) uptake and significant risk of premature cardiovascular disease.

For more than a decade, the American Academy of Pediatrics has recommended universal screening between nine and 11 years of age (and earlier screening if there are additional risk factors), and the European Atherosclerosis Society and the American College of Cardiology/American Heart Association recommend beginning treatment with statins for affected children. Adherence to these recommendations has been limited because of the uncertain benefits and risks of starting asymptomatic children with a genetic disorder on powerful medications.

This is why a recent study in the New England Journal of Medicine reporting significant benefit of statins in this population at 20-year follow-up is a really big deal. The baseline study two decades ago looked at the safety of two years of statin therapy on a cohort of children with genetically proven heterozygous familial hypercholesterolemia, their unaffected siblings, and affected parents. The current follow-up study examined 214 of the affected children (now adults), their 156 affected parents, and 95 unaffected siblings. Participants gave medical/lifestyle information and had fasting lipid testing with carotid ultrasound measurements at mean age 31 years. Follow-up rates from the original study were high; 86 percent of patients and 81 percent of unaffected siblings participated. Data about cardiovascular events and death were available for 95 percent and 100 percent of patients respectively.

At follow-up, 416 patients (79 percent) were still taking pravastatin. Only eight of the 214 patients (3.4 percent) at follow-up had an LDL level less than 70 mg/dL, but their mean LDL cholesterol level was 32 percent lower than baseline, and in 20 percent the LDL was less than 100 mg/dL. At baseline, the affected children had significantly higher carotid wall thickness compared with their siblings, but this difference and the rate of carotid thickening were not significant at follow-up. Most importantly, the cumulative cardiovascular disease-free survival of patients at age 39 years was 99 percent compared to 74 percent for their affected parents (adjusted hazard ratio 11.8, 95% CI 3-107). The single patient who experienced angina and had a stent placed at age 28 had not taken statins since the original two-year trial period in his childhood. Remarkably, the rate of death from cardiovascular events was zero percent in patients compared with seven percent of affected parents, with all deaths in parents occurring due to myocardial infarction before age 40.

Certainly, there are limitations to this study, such as the use of parents as historical controls as opposed to an active control group of patients with familial hypercholesterolemia not initiating statins early. This study did not address potential morbidity and fetal loss related to the risk of teratogenicity in pregnant women or adolescents taking statins, or the effect of statins on all-cause mortality. Nevertheless, this study is a game-changer. We now have evidence that initiating statin therapy in children with familial hypercholesterolemia may decrease the risk of cardiovascular events and cardiovascular mortality in adulthood. This reinforces current recommendations to screen, diagnose, and treat familial hypercholesterolemia not just in adults but in children.

For more information, see the topic Familial Hypercholesterolemia in DynaMed

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