Statin Initiation in Children With Familial Hypercholesterolemia Decreased Adult CVD Risk
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficacy of statin therapy in children is well established, but longer follow-up studies evaluating changes in the risk of cardiovascular disease are scarce.
METHODS
We report a 20-year follow-up study of statin therapy in children. A total of 214 patients with familial hypercholesterolemia (genetically confirmed in 98% of the patients), who were previously participants in a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, were invited for follow-up, together with their 95 unaffected siblings. Participants completed a questionnaire, provided blood samples, and underwent measurements of carotid intima-media thickness. The incidence of cardiovascular disease among the patients with familial hypercholesterolemia was compared with that among their 156 affected parents.
RESULTS
Of the original cohort, 184 of 214 patients with familial hypercholesterolemia (86%) and 77 of 95 siblings (81%) were seen in follow-up; among the 214 patients, data on cardiovascular events and on death from cardiovascular causes were available for 203 (95%) and 214 (100%), respectively. The mean LDL cholesterol level in the patients had decreased from 237.3 to 160.7 mg per deciliter (from 6.13 to 4.16 mmol per liter) - a decrease of 32% from the baseline level; treatment goals (LDL cholesterol <100 mg per deciliter [2.59 mmol per liter]) were achieved in 37 patients (20%). Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm per year in patients with familial hypercholesterolemia and 0.0057 mm per year in siblings (mean difference adjusted for sex, -0.0001 mm per year; 95% confidence interval, -0.0010 to 0.0008). The cumulative incidence of cardiovascular events and of death from cardiovascular causes at 39 years of age was lower among the patients with familial hypercholesterolemia than among their affected parents (1% vs. 26% and 0% vs. 7%, respectively).
CONCLUSIONS
In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood. (Funded by the AMC Foundation.).
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Additional Info
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20-Year Follow-Up of Statins in Children With Familial Hypercholesterolemia
N. Engl. J. Med 2019 Oct 17;381(16)1547-1556, IK Luirink, A Wiegman, DM Kusters, MH Hof, JW Groothoff, E de Groot, JJP Kastelein, BA HuttenFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Genetic causes of hypercholesterolemia pose a challenge for pediatricians—although it’s clear that elevated cholesterol over time is deleterious to health, traditionally the field of pediatrics has not had to rely on the use of cholesterol-lowering medication, such as statins, anywhere near as much as in adults. This lack of familiarity means that pediatricians are reluctant to prescribe statins, and even those in fields like family medicine may be uncertain as to whether there is true long-term benefit from doing so.
In this study, 214 patients with familial hypercholesterolemia (so, mind you, not from other causes, such as poor diet) were followed for 20 years. They all had been placed on pravastatin; the control group was unaffected siblings. They found that LDL cholesterol levels declined 32% from baseline, and treatment goals were achieved in 20% of the patients. (Details of goals are outlined in the paper.)
However, did the decrease in laboratory values mean anything? They found that not only did progression of carotid intima-media thickness slow down, but the cumulative incidence of cardiovascular events and death from CV causes by age 39 was lower than in their affected parents (1% vs 26% for CV events; 0% vs 7% for deaths).
These are fairly good data, and argue for the long-term benefit of statin therapy. However, I’d like to see a study with a larger population. There’s some excellent discussion of limitations (particularly around the ethics of not using a placebo treatment group) in the paper. There’s also very little discussion or analysis of side effects, which is a significant concern for clinicians. This study alone is reassuring in terms of benefit, but I’d like to see it coupled with other long-term work to address these other areas.