Having a Ball: What Can Be Done About Pediatric Dyslipidemia?

EN March 24 Cover
Children who are physically inactive may have high cholesterol in early adulthood and subsequent heart health issues in their mid-forties, according to new research published in The Journal of Clinical Endocrinology & Metabolism. Study author Andrew O. Agbaje, MD, MPH, FESC, talks to Endocrine News about the study’s findings, the arbitrary nature of some guidelines, and why pediatric lipid screening should be more common.

For generations, moms and dads have been urging their children to “go outside and play!” Whether those well-meaning parents were concerned with their kids’ high cholesterol levels or simply wanted to get them off the couch and into the sunshine, we’ll never know for certain.

However, a study published in the December 2023 issue of The Journal of Clinical Endocrinology & Metabolism does show for certain is that high levels of cholesterol during childhood has been associated with early signs of heart disease when sedentary kids reach their mid-twenties, as well as an increased risk of premature cardiovascular death when they are in their mid-forties. Furthermore, several clinical trials aimed at lowering cholesterol levels in the youth population have had minimal or no effect.

In “Associations of Sedentary Time and Physical Activity From Childhood With Lipids: A 13-Year Mediation and Temporal Study,” study author Andrew O. Agbaje, MD, MPH, FESC, of the Institute of Public Health and Clinical Nutrition, School of Medicine, Faculty of Health Sciences, University of Eastern Finland in Kuopio, and a Harvard-certified clinical researcher makes child’s play of how to prevent dyslipidemia. In the process, Agbaje turns entrenched beliefs about physical activity on their heads.

Origin Story

Using data from 792 “children of the 90s” from the University of Bristol’s Avon Longitudinal Study of Parents and Children (ALSPAC), in England, Agbaje’s study aims to fill a gap in current understanding of the relationship between physical activity in childhood and adult cardiovascular health. While we have long suspected that sedentary time has deleterious effects on lipid indices, insufficient research has been done on the optimal way to reduce sedentary time (i.e., increase physical activity).”

According to the World Health Organization’s (WHO’s) “WHO guidelines on physical activity and sedentary behaviour,” from 2020, “Children and adolescents should do at least an average of 60 minutes per day of moderate-to-vigorous-intensity, mostly aerobic, physical activity, across the week.” The Centers for Disease Control and Prevention recommend the same.

The WHO also points out that current evidence suggests that 80% of children and adolescents do not meet this guideline. These metrics sent Agbaje on a quest. “Why 60 minutes?” he asked. “Why not 75? Or 50? Then I also recognized that telling adolescents that 80% of you do not meet the guideline is telling them that they are failures, when they are not. People don’t naturally accumulate 60 min/day of moderate-to-vigorous-intensity physical activity (MVPA). Specialized athletes choose to do this, but we are not designed to do this. What we are designed to do is to walk.” Agbaje says that in addition to the adolescent mental health hit this message delivers, it also affects parents, who likewise feel like failures for not succeeding in pushing their children to achieve 60 min/day of MVPA.

“I began to see the problems of the 60-minutes-per-day guideline — how ineffective, arbitrary, and unsustainable it is and the consequences of this negative publicity to adolescents. So what is the benefit? There must be a paradigm shift,” he concludes, “but before I can speak about paradigm shifts, there must be evidence.”

Another problem with the WHO guideline — one they cite as a limitation — is that the threshold at which sedentary time becomes harmful is not known, so they simply advise reducing it. “This is not a guideline,” Agbaje says. “You don’t leave people in limbo; we must be concrete.”

Universal Pediatric Lipid Screening?

Agbaje says that ALSPAC data showed sedentary time measured by accelerometer worn for seven days at three time points increasing from six hours per day in childhood to eight hours per day in adolescence and to nine hours per day by young adulthood, an increase driven largely — no surprise — by screen time. He also analyzed measurements of complete fasting plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol taken at each of three follow-up visits at ages 15, 17, and 24 years. “When we cumulatively looked at that sedentary time and its impact on cholesterol level, it was alarming to see that sedentary time independently contributed nearly 70% to the total increase in cholesterol level from the age of 15 to the age of 24.”

“We [recently] found that increasing cholesterol level within the space of seven years [between ages 17 and 24 years] increased the risk of premature heart damage by 20%. We now realize that sedentary time was at the root of all of the problems, not even the cholesterol itself. The cholesterol now looks like an intermediate.” — Andrew O. Agbaje, MD, MPH, FESC, Institute of Public Health and Clinical Nutrition, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio

Add this to the findings from Agbaje’s previous studies that: 1) elevated pediatric lipid levels are linked to subclinical atherosclerosis in the mid-20s; 2) a simulated intervention in late adolescence (around age 17) was shown to ameliorate the pathophysiologic mechanisms driving atherosclerosis; and 3) other researchers have reported pediatric dyslipidemia–related premature cardiovascular mortality in the mid-40s, and an important takeaway for clinicians emerges: “there should be universal pediatric lipid screening,” Agbaje says.

But there’s more. “We [recently] found that increasing cholesterol level within the space of seven years [between ages 17 and 24 years] increased the risk of premature heart damage by 20%,” Agbaje says. The current study, however, revealed some additional unpleasant surprises. “We now realize that sedentary time was at the root of all of the problems, not even the cholesterol itself. The cholesterol now looks like an intermediate,” he explains.

“The one out of five who develop heart disease is one too many, when this is preventable. Also, when many of these heart diseases eventually occur, we can’t cure them, we can only manage them for life, which increases healthcare costs, yet it’s so cheap to measure cholesterol levels.” Current guidelines recommending cholesterol screening at age 40 are woefully misguided. At that point, any damage to the cardiovascular system that has occurred is probably irreversible, and the health care cost burden spirals.

Finding Middle Ground

So, sedentary time is profoundly harmful, yet 60 min/day of MVPA is an unrealistic target — where do we go from here? Fortunately, there is an extremely effective — yet systematically overlooked — middle ground: light physical activity (LPA). For children and adolescents, LPA can take many easy-to-come-by forms like walking, riding a bike, and even playing on the playground. The irony will be lost on no one that this is precisely what childhood used to look like.

Agbaje’s study showed that time spent in MVPA does not change significantly from childhood to young adulthood, but what does change is the amount of time spent sedentary, and this extra time has been “stolen” from time that had been spent in LPA. “Our study showed that we need at least three to four hours of light exercise every day to be able to counter the effects of sedentary time. Up to six hours of light exercise every day is the optimal amount, but, realistically, as we grow and get involved in classes and work, our time is being fought for by many responsibilities. So our studies have shown that if we can get three to four hours of light exercise every day, we can antagonize all the negative effects of sedentary time.” In other words, LPA completely reverses that 70% increase in total cholesterol level from age 15 to 24 and therefore also obviates its negative downstream effects, such as subclinical atherosclerosis and premature heart damage.

LPA has other advantages as well, such as being accessible to most people, whereas not everyone can participate in MVPA for various health reasons. LPA also can be implemented gradually and systematically until it becomes what Agbaje called an “autopilot of positivity” (as compared to the “autopilot of negativity” that sedentary time induces).

That this is great news is clear, but why no recommendation exists for a specific sedentary threshold, which equates to increasing LPA, is not. This is where Agbaje’s paradigm shift is critical. “What we have been pushing does not work. MVPA is not the right solution for sedentary time.”

“I Need to Fight for the Kids”

To be clear, Agbaje is not decrying MVPA, which certainly has many overall health benefits, but he is saying that it is not going to improve cholesterol parameters as effectively as LPA can because increased sedentary time is driving cholesterol increases, and the increase in sedentary time was bought at the expense of time spent in LPA. LPA also has the upper hand because its effects on cholesterol reduction are long-lasting, whereas the effects of MVPA diminish soon after exercise ceases, mediated by fat mass.

“I began to see the problems of the 60-minutes-per-day guideline — how ineffective, arbitrary, and unsustainable it is and the consequences of this negative publicity to adolescents. So what is the benefit? There must be a paradigm shift, but before I can speak about paradigm shifts, there must be evidence.” — Andrew O. Agbaje, MD, MPH, FESC, Institute of Public Health and Clinical Nutrition, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio

Ultimately, spending time in both MVPA and LPA while reducing time spent sedentary is the optimal approach to overall health from a physical activity standpoint. These findings are also true for adults — increasing LPA improves several health parameters and lowers the risk of various diseases — but Agbaje will keep his research focus on younger populations. “They don’t have many voices. I need to fight for the kids.” Prevention, he believes, through decreasing sedentary time and instituting pediatric cholesterol screening, is the turning point in this fight against dyslipidemia.

The study was funded by the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Yrjö Jahnsson Foundation, the Jenny and Antti Wihuri Foundation, the Orion Research Foundation, the Aarne Koskelon Foundation, the Paulo Foundation, the Paavo Nurmi Foundation, and the Ida Montinin Foundation.

Horvath is a freelance writer based in Baltimore, Md. In the February issue, she talked with 2024 Transatlantic Award winner Felix Beuschlein, MD, about his career and research.

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