Universal Lipid Screening, Statins for Children?

Yesterday, a little girl in clinic excitedly told me all about why purple is her signature color, and then demonstrated her latest gymnastics skills. This morning, I met a little boy with type 1 diabetes who named his dogs after his favorite superheroes—Captain America, Thor, and Ironman—and who plans to become a veterinarian like his mother. I delight in my patient population, and this is what compelled me to pursue a pediatric specialty.

I especially enjoy the ability to provide true preventive care. During internal medicine rotations as a medical student, I grew frustrated as I begged patients to stop smoking, to start exercising, or to change the diet they had been following for decades. With children, we have a blank canvas. I counsel them to avoid tobacco, while their parents and grandparents (who are often unable to quit) sheepishly join me in my warnings to never start smoking. I can't convince a 40-year-old dad to take up Zumba or incorporate kale into his diet, but kids have a greater sense of adventure and may give it a try.

Children respond beautifully to encouragement and positive role models. True primary prevention (ie, primordial prevention) starts in childhood, and clinicians who care for children are positioned to prevent lifelong illness and morbidity.

Stopping Disease Before It Starts

What is the best way to avoid a lifetime of obesity and its complications? Not gaining the weight in the first place.^[1] What's better than stenting to open coronary arteries? Preventing atherosclerosis by modifying known risk factors.

Epidemiologic studies—from the Bogalusa Heart Study^[2] to the Framingham Heart Study^[3]—have identified many risk factors for coronary artery disease, including elevated low-density lipoprotein cholesterol (LDL-C) levels, smoking, and sedentary lifestyle. One of the most powerful ways to prevent coronary artery and cerebrovascular diseases is to modify LDL-C levels by treating at-risk patients with statins. Multiple studies have shown that they prevent the development of atherosclerosis by lowering LDL-C levels.^[4]

The 10-year Framingham risk calculator for general cardiovascular disease is used to guide treatment decisions. For almost all children, the 10-year risk for myocardial infarction is close to nil, so identifying subtle variations in lipids will rarely lead to pharmaceutical interventions.

But for those rare patients with genetic lipid metabolism disorders that cause extreme elevations in LDL-C, early identification and sometimes treatment is crucial. Familial hypercholesterolemia (FH), an autosomal codominant condition that causes impaired LDL-C clearance, is the primary concern. It is estimated to affect 1 in 500 people in certain populations.^[5]

Screening for FH

Screening in early puberty proves to be the ideal window in which to identify those with genetic dyslipidemias who will be at higher risk for cardiovascular disease later in life. Children at these ages are still getting scheduled primary care, and statin therapy is not recommended until at least Tanner developmental stage II because of theoretical effects on sex-steroid metabolism. Thus, universal screening has been recommended between age 9 and 11 years,^[6] with recommendations to consider statin therapy for those with an LDL-C level > 190 mg/dL (normal, < 100 mg/dL) in the absence of other risk factors.

Children are ideal targets for primary prevention because pediatric patients come to their visits regularly. We see most kids at least annually for preventive care, especially corresponding with mandatory vaccines as required by schools. After childhood, it is common for people to avoid medical care for years, often surfacing only after catastrophe, even with insurance coverage in the era of very high-deductible plans.^[7]

People don't avoid seeing physicians just because they stop getting lollipops and stickers at visits. Of the 95% of US children who have insurance, 39% receive their medical coverage from Medicaid and risk losing this coverage at adulthood.^[8] Thus, diagnosing treatable congenital and hereditary illnesses in childhood becomes particularly urgent.

During initial visits with newly diagnosed lipid derangements, I am often astonished at how many parents have never had cholesterol checks themselves or misunderstood the results.

By definition, if a child has FH, at least one parent will be affected, barring a rare, spontaneous mutation. In my practice, I frequently diagnose parents in their 30s and 40s with much higher Framingham risk scores than their children, and meaningful intervention is possible.

Diet and Exercise Not Always Enough

There is profound misunderstanding about who benefits from lipid screening, and adherence to the National Heart, Lung, and Blood Institute (NHLBI) guidelines has been poor.^[9] Medical professionals and the lay public alike attribute the rise of dyslipidemia diagnoses to the childhood obesity crisis.

Although mild variations in triglycerides and high-density lipoprotein cholesterol (HDL-C) are possible with abnormal weight gain and especially insulin resistance associated with central obesity, obesity alone does not cause LDL-C changes great enough to reach the threshold for statin initiation in the pediatric population. Serious dyslipidemias that would require early intervention are caused by genetic defects in processing LDL-C, and lifestyle has little influence on these levels.

I think of one patient, a 16-year-old cross-country runner who followed an admirable diet. His LDL-C level before starting statin therapy was always > 250 mg/dL, despite his best efforts. His mother, who had been on statin therapy since her 20s (with the exception of pregnancy), had a similar lipid profile off therapy. Fortunately, she has avoided the myocardial infarction her father had suffered at age 41 with appropriate preventive therapy. Diet and exercise do not fix a faulty LDL receptor.

A limiting factor in the underserved area in which I practice, beyond ignorance of the NHLBI prevention guidelines^[9] (endorsed by the American Academy of Pediatrics and the American Heart Association), is confusion regarding what to do with the results of lipid screening tests. Lipid specialists are rare, and lipid specialists with pediatric expertise are almost impossible to find. Depending on the institution, pediatric endocrinologists, pediatric cardiologists, or pediatric gastroenterologists may be the first stop if there is not an established pediatric lipid clinic.

Regional referral patterns vary widely. Regardless, the old proverb about a bird in the hand holds true here. It is more common for people to seek preventive care for their children than for themselves. After initial universal screening at age 9-11 years, repeat screening is recommended at age 17 years, right before launching into the more fragmented world of adult medical care.

Healthy Lifestyle Habits Still Valuable

Universal lipid screening affords us a window to encourage children and their families to take prevention of cardiovascular disease seriously, every day of their lives. Even for kids without serious genetic dyslipidemias, discussing screening gives pediatricians and family physicians the opportunity to focus on cardiovascular disease prevention strategies that are important for every patient.

Lipid metabolism problems other than FH may be revealed by lipid screening, and the cornerstone for managing minimally elevated LDL-C, mildly elevated triglycerides, and low HDL-C in childhood is still lifestyle counseling. Identifying any lipid derangements may be an impetus for children and families to modify health behaviors while they are malleable.

The dividends from counseling to prevent cardiovascular disease will significantly affect other disease states; children who become adults who don't smoke, maintain a normal body mass index, and exercise regularly will be less likely to develop other life-limiting diseases as well.

Also of great importance, children with the most serious genetic dyslipidemias will begin adulthood healthy, with a lower risk for early myocardial infarction. As a pediatric endocrinologist, I am thankful for every opportunity to discuss preventive healthcare and create a ripple effect into the child's family and community, to truly effect well-being at a population level.

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