COMMENTARY

The Secret to Primary Prevention of CVD? Start With the Kids

Don Wilson, MD

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March 23, 2021

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This transcript has been edited for clarity.

I'm Dr Don Wilson, a pediatric endocrinologist at Cook Children's Fort Worth Hospital in Texas. My presentation at the 2021 Endocrine Society Annual Meeting reflected on the need for pediatricians and endocrinologists to become increasingly aware of dyslipidemia in children.

Starting in the 1990s with the National Cholesterol Education Program (NCEP), we started to recognize that there was a huge opportunity to focus on dyslipidemia in children with the intent of trying to do true primary prevention. The focus then translated in 2011 to the expert panel recommendation to do routine screening of children. That effort usually starts at around 10 years of age — or 2 years and older in kids who have other conditions or whose parents are known to have hypercholesterolemia, are taking medications, or have a rampant family history of cardiovascular disease, etc. But for those kids who are asymptomatic and just routinely seen by pediatricians and family physicians, that effort usually starts at around 10 years of age.

Familial Hypercholesterolemia

What we're looking for is familial hypercholesterolemia (FH) or elevated LDL cholesterol, which we know is associated with cardiovascular disease in the adult. But this is a genetic variant that causes high cholesterol and translates into cardiovascular disease that can be prevented — not the genetic mutation, but the consequences of it. The key to it, as many of us have recognized, is trying to identify the children at a very young age. That screening can be done with a nonfasting sample, which is a bit more practical in practice situations. And then you can take that information, take a careful history, and ultimately recommend cascade screening.

Cascade screening means that FH is a co-dominant condition, meaning that about half the family members may be affected, or at least the siblings. We've seen a lot of parents who have not been diagnosed. Those parents are older, so they're closer to an event than the children would be. So there's a huge return because FH is very common, seen in about 1 in 200 children. As a consequence of identifying that child, we can kind of go upstream, if you will, and identify the siblings, mother, father, grandparents, aunts, and uncles. And it's been very rewarding.

FH is a genetic mutation that is really going to benefit from lipid-lowering medications. All of the statins have been FDA-approved for use in children starting at about 8-10 years of age. They have 20-year follow-up data in patients who are in their 40s now, showing that they have been remarkably safe and remarkably effective. If you look at FH children who were treated from their teenage years until their 40s, you see that they don't have any events compared with their parents. And their arteries look exactly like those of their siblings who are not affected.

So, we know that early identification can translate into at least 20 years, if not longer, of improvement in those things that will ultimately lead to coronary artery disease. As we all know, coronary artery disease, atherosclerosis, and their consequences are the leading causes of morbidity and mortality — not only in the United States but in all developed countries.

Lifestyle Issues

In addition to FH, there are also a growing number of dyslipidemias as a result of lifestyle issues. They may also have an undercurrent of genetic mutations, but these are not monogenic disorders; for the most part, they are polygenic or epigenetic phenomena that usually manifest in an environment where you have secondary risk factors, such as obesity, high-fat/high-calorie diets, or medication effects. These are picked up from routine screening, or sometimes pediatricians or family physicians would screen kids who meet certain criteria (for example, they have obesity, acanthosis, prediabetes, or diabetes).

When those are detected, the effort is not so much on medication as it is on lifestyle. There's a lot of education, a lot of encouragement, and a lot of coaching for these children. I think it's a great investment, the sooner you start with that. In fact, you don't need a lipid screening in children who are starting to gain weight at an early age because that's the best time to try to intervene and get them to learn that healthier lifestyles will translate into healthier lives. A lot of that effort is focused on parents, trying to get them to set a good example for their children. In fact, the best approach is family-based. If you get the entire family to adopt a healthy lifestyle for the child, the entire family would benefit.

Rare Syndromes

There are some occasions where kids do have genetic mutations, such as familial chylomicronemia syndrome, but those are extremely rare. Children who have triglycerides in excess of 1000 mg/dL or 10 mmol/L are much more likely to have some type of underlying genetic mutation: either a monogenic disorder, which is very rare — we call that familial chylomicronemia syndrome — or a polygenic or epigenetic phenomenon, which is amplified by environmental factors.

Most of the children are going to be somewhere between 250 and 450 mg/dL. Children in that group, particularly between 150 and 500 mg/dL, are the ones in whom we're concerned about increased cardiovascular risk long-term because they have high triglycerides and their small dense LDL levels are increased. You can see that if you calculate the non-HDL cholesterol (take total cholesterol, subtract out the HDL, and you're left with all of the apo B or atherogenic particles). So that's a great way to screen those kids and also to follow them. The nice thing about that particular test is you don't have to do it fasting.

But again, those kids are going to benefit a lot from meeting with a registered dietician or nutritionist, being encouraged to become physically active, working with people in the community and their schools to enhance physical activities, and working with your community to create opportunities for parks and other recreational things that children can get out to do. These are mostly commonsense things, but they need to be said and they also need to be done. A lot of pediatricians and family physicians are very good at motivational-type things where they try to get kids engaged.

Ultimately, I think all of these efforts are really focused on trying to create a healthy future for these children. And I think if we start early, we can do a great job.

Don Wilson, MD, is an expert in the field of pediatric clinical lipidology. He serves as the endowed chair of the Pediatric Cardiovascular Health and Risk Prevention program at Cook Children's Medical Center in Fort Worth, Texas, and is a co-author of the National Lipid Association's recommendations for patient-centered management of dyslipidemia.

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