An emerging dyslipidemia: New NHLBI and NLA treatment guidelines

Key Points

There remains considerable controversy over the use of pharmacologic treatments to lower blood lipids in children. The last decade has seen significant advances in this area, but these have not eliminated controversy.

The literature on pharmacologic treatment has recently been summarized in an American Heart Association statement on the treatment of dyslipidemias in childhood and forms part of the evidence base for the expert panel recommendations.¹

From this work, it is clear that some children and adolescents, particularly those with familial hypercholesterolemia, end-stage renal disease, diabetes mellitus, Kawasaki disease, and other multiple-risk states, have significant acceleration of atherosclerosis. Studies of adolescents and young adults have shown that statin treatment slows the progression of carotid intima thickening and that the younger the age treatment is initiated, the better the results.⁴

A second argument relates to results of randomized, controlled trials of statins in children. These studies have been conducted with all the major statins, with studies lasting for as long as 2 years.¹ They show significant cholesterol lowering and absence of significant adverse effects, including problems with growth, passing through puberty, liver function, or muscle injury.

There are decades of experience with these agents in adults, and although there are issues with drug intolerance, this seems to occur mostly in older patients taking multiple medications, including statins. Now there is substantial pediatric experience with these agents acquired over the last 2 decades in specialty clinics, and severe adverse events have not been reported. As a result of this work, statins have become the agents of choice for treating dyslipidemia, replacing the poorly tolerated resins and niacin. Statins remain contraindicated during pregnancy and breastfeeding.

A third argument for the early use of statins relates to the impossibility of conducting randomized trials in children and waiting for cardiovascular endpoints decades later. It seems unethical to withhold effective treatment from persons at high risk in much the same way that one would not randomize children to tobacco exposure just to be sure of the adverse effects.

Essentially, all the components of the argument for treatment are present, particularly when adult studies are considered. This argument unfortunately does not provide a basis for determining the optimal time to initiate medication or establish a goal for treatment.

Currently, the only evidence for cholesterol-lowering goals relates to secondary prevention (treatment after an event has occurred). It is hoped that subclinical atherosclerosis measures may help establish these targets, but the clinical usefulness of these tests remains uncertain in adults.

A different approach has been taken in Europe. Experience with familial hypercholesterolemia in large clinical programs has led to a much more organized approach to the disease, including large cohort studies to assess natural history.

In particular, familial hypercholesterolemia has been considered a separate disease entity, distinct from conventional population-based guidelines ( http://www.nice.org.uk/CG71).

Cost-benefit models constructed in the development of this guideline suggest that there was cost benefit in early identification, including both genetic testing to identify the specific genetic defect and initiation of statin treatment in children.

A controversy erupted when the American Academy of Pediatrics (AAP) nutrition guidelines were updated in 2008.⁵ The recommendation was made that statins could be initiated in children as young as 8 years in selected high-risk patients.

This recommendation was widely misinterpreted as saying that many children, including those with obesity, would get medication. The rationale for this change from 10 years to 8 years in the guidelines was that some of the statins were approved for use down to 8 years on the basis of clinical trial data, and the guideline authors felt compelled to include mention of treatment at this age.

The written guideline is essentially consistent with all lipid treatment guidelines published since the 1992 National Cholesterol Education Program report.⁶ Statins are reserved for use at this young age only for those with the most extreme risk (ie, genetic dyslipidemias), and the widespread use of statins in children is not recommended.

It is important to remember that the dyslipidemia associated with obesity is not increased low-density lipoprotein (LDL) cholesterol but rather high triglycerides, low high-density lipoprotein (HDL) cholesterol, and the creation of an atherogenic lipoprotein profile. Therefore, statins are not a treatment for the dyslipidemia of obesity.

There are no randomized trials of agents to lower triglycerides in children (or to raise HDL cholesterol), and there is no evidence from randomized trials in adults that lowering triglycerides or raising HDL cholesterol alters cardiac disease rates in primary prevention in adults.

The question that may be answered in the next decade or so is the role of statins in overall risk reduction. Currently these facts are known: 1) After a cardiovascular event, statin treatment reduces risk of future heart attacks at LDL levels above 70 mg/dL; 2) atherosclerosis is related to risk factors other than LDL cholesterol; and 3) LDL reduction in adults without severe elevations of LDL cholesterol but in the presence of other risk factors (eg, increased C-reactive protein) lowers event rates.