Is it for real? Cholesterol screening in toddlers and statins from elementary school age?
You’ve no doubt heard the news that “Obese kids may be candidates for cholesterol drugs.” New clinical guidelines from the American Academy of Pediatrics call for cholesterol screening in children from age two; low-fat dairy from age one in all kids; and cholesterol-lowering drugs, namely statins, for children as young as eight. These clinical guidelines have generated considerable controversy. But there’s something you need to know.
The controversy is not a matter of differences in opinions over the scientific evidence. This is a matter of the scientific evidence versus opinions and agendas.
To best understand the lack of evidence, misinformation and cognitive disconnects in these guidelines, we’ll go directly to the guidelines themselves and the evidence the authors cite.
The introduction states that these new guidelines take “on a new urgency given the current epidemic of childhood obesity.” This report overturns the 1998 AAP policy, according to lead author Dr. Stephen R. Daniels, M.D. and colleagues, and was made imperative because of new data on the negative effects of fattening diets, decreased physical activity, and the metabolic syndrome, and these risk factors for adult-onset cardiovascular disease. Because risk factors may begin at a young age, the authors said, it necessitates that pediatricians “initiate [a] lifelong approach to prevention of CVD in their patients,” and focus on “improving lipid and lipoprotein concentrations during childhood and adolescence to lower the lifelong risk for CVD.”
As it turns out, their paper is unable to support any of these claims.
Fallacy: kids are little adults
They begin by claiming that healthy toddlers and young people should be treated like adults with heart disease. They argue that reducing cholesterol levels in children to levels used in the secondary preventive management of adults with heart disease can prevent cardiovascular disease.
Confusing secondary preventive interventions with primary prevention is a mistake that’s unconscionable medical professionals would actually make, as they address different physiological processes. But they also provide no evidence for their view that lowering cholesterol levels in growing kids is effective for the primary prevention of cardiovascular disease in adulthood. Because there isn’t any.
Nor do they provide any evidence to support their belief that the range of cholesterol levels normally seen in childhood in any way predicts risks for future heart disease in adulthood. Because there isn’t any.
More worrisome, they fail to recognize that lipids and fats benefit growing children and teens and are needed for normal neurological and cognitive development, protein synthesis for growth, energy needs and in hormones for puberty and maturation. The possible risks for lowering cholesterol below what’s normal among growing children and teens wasn’t explored at all.
Fallacy: the bait and switch
ALL of the evidence to support concerns of cardiovascular disease risks associated with “high” cholesterol comes from research in patients with familial hypercholesterolemia (FH), an exceedingly rare genetic disorder associated with extreme elevations in total cholesterol and LDL-cholesterol levels. These aren’t the levels popularly believed to be “high,” these are off the chart levels. The heterozygous form of FH causes levels at least twice normal, and the homozygous form results in cholesterol levels of 700-1,000 mg/dl.
More importantly, obesity has nothing to do with the development of this genetic disorder. Nor will weight loss, diet or exercise cure or prevent it. True high cholesterol has nothing to do with obesity.
Just because an extreme level — multiple times normal or off the chart levels — is associated with a health problem, does not mean that the ranges found in virtually all children and adults hold similar danger. But it’s the classic bait and switch. Arbitrarily redefining “high” cholesterol to include the upper ranges of normal has taken in countless people and led them to worry that they are at risk and are in need of medical intervention. But it’s a fallacy. [Covered here.]
As Dr. Harumi Okuyama of the departments of Biological Chemistry and Pharmaceutical Sciences at Nagoya City University in Japan, has explained, once cases of genetic familial hypercholesterolemia are removed from population statistics, “high” cholesterol isn’t a causal factor for heart disease at all.
Among the leaders of this fallacious argument being used to promote the need for widespread screening and for medical management of cholesterol, along with the other health indices in the “metabolic syndrome,” are the American Heart Association and National Cholesterol Education Program (NCEP) of the National Heart, Lung, and Blood Institute.
Redefining normal as “high”
This fallacy was also seen used in guidelines recently released by the AHA for the use of statins in kids. [Covered in detail here.] As Dr. Ian Janssen at Queens University in Ontario, Canada, had explained, these new AHA-NHLB cut-offs, used to identify young people with “high” levels for total, LDL- and HDL-cholesterol and triglyceride levels, were “chosen arbitrarily and have no clinical or health meaning.”
As Dr. Janssen said, the AHA had simply improvised a lipoprotein growth curve, adding arbitrary 5th, 25th, 50th, 75th, and 95th percentiles and extrapolating levels corresponding to adult risks. Not only do normal lipoprotein levels vary considerably during growth and maturation, by the seasons, from day-to-day, and by gender, no researcher has ever found a link between these new arbitrary thresholds in young people and cardiovascular disease.
Daniels and colleagues have used similar arbitrary cutoff points for their new recommended cholesterol, LDL and HDL-cholesterol and triglyceride levels, based on ranges seen in children in the Lipid Research Clinics. An “abnormally high” value (in “need” of intervention) was arbitrarily defined as any level at and above the 95th percentile (or so they said).
But, remember, true hypercholesterolemia is rare — the homozygous form is found in about 1 in a million people and the heterozygous occurs in about 1 in 500 people worldwide. That’s 0.0001% to 0.2% of people — not 5%.
Guidelines for rare medical conditions that affect 0.0001% to 0.2% of the population would, in the real world, be written in an obscure specialty journal and never make international news. Ask yourself why this one has. Might it be that this isn’t really about evidence-based medical management of an actual clinical condition, but creating one?
Cholesterol is often used as a surrogate marker for identifying adults most at risk for cardiovascular disease, the AAP authors said, [which we’ve seen doesn’t predict cardiovascular disease, either]. But in kids, they said:
Unfortunately, no similar risk score is available for children. Also,data supporting a particular level of childhood cholesterol that predicts risk of adult CVD do not exist, which makes the prospect of a firm evidence-based recommendation for cholesterol screening for children elusive.
Yet, incredibly, without any evidence at all, they went ahead and made up recommendations anyway!
They recommended all children be screened beginning at age two who have a family history of ‘high’ cholesterols or premature heart disease, or any risk factors such as being overweight, smoking, diabetes, hypertension, or where family risk factors is not known. Clearly, this could be used to target practically all kids, especially among practitioners who don’t understand what medical “high” levels mean.
But, remarkably, the authors lamented that these targeted screening strategies could miss 40-70% of kids who could be identified for cholesterol treatment. Then, in the next passage, they turned around and admitted that an “unanswered question is whether the lack of identification and treatment of those children [actually] leads to increased risk of CVD development.”
Their recommendations for cholesterol screening of children and teens are the opposite of the recommendations recently issued by the U.S. Preventive Services Task Force, after its experts conducted a systematic review of 25 years of evidence. [The evidence on cholesterol screening was covered in depth in this article for parents wondering if they should have their child or teen screened.]
The USPSTF had concluded that the evidence is insufficient to recommend routine screening for lipid disorders in infants, children, adolescents or young adults. Evidence for effectiveness is “lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined,” they stated.
Not only do elevated lipid levels in growing young persons not predict high levels or heart disease in adulthood, the USPSTF found, there is no evidence that any intervention to lower cholesterol levels in childhood “leads to improved lipid profiles or better health outcomes in adulthood.” Worse, they identified serious potential harms of dietary and pharmacological interventions attempting to reduce cholesterol levels in young people.
Leading everyone to feel at risk and in need of attention
Daniels and colleagues claimed that the obesity epidemic calls for the urgent need of population-wide measures to lower cholesterol levels. While this perpetuates popular beliefs that obesity causes ‘high’ cholesterol and heart disease, and that weight loss helps prevent heart disease, it’s another disconnect with the evidence. Remember, obesity doesn’t cause true high cholesterol.
Nor has there been an epidemic of high cholesterol levels among the population, as they themselves noted. National Health and Nutrition Examination Surveys (NHANES) data shows there’s been no increase in lipid and lipoprotein levels in children, adolescents or adults since at least the 1960s — levels have even decreased. Between 1966-1970 NHANES and 1988-1994, average total cholesterol levels in children and teens ages 4-19, dropped an average of 7mg/dl. And, just during the 12 years between 1988-1994 and 1999-2000 NHANES, triglyceride levels dropped about 8.8 mg/dL in adolescents aged 12 to 17 years, and total cholesterol, LDL, and HDL levels have stayed the stable.
There is no epidemic of children with high cholesterol, but the authors’ newly-created cut-offs for the 50th percentile at each age, deemed “acceptable levels,” are below the average levels among U.S. children and teens recorded in the NHANES. Cholesterol levels also naturally rise as kids get older and enter puberty, especially girls and minorities. In other words, as more kids are screened under these guidelines, suddenly most will now find themselves diagnosed with “high” or “borderline high” levels and in need of intervention!
The authors called for a population approach that focuses on healthy lifestyle interventions for all children, especially targeted towards kids at ‘high risk’, to reduce cholesterol levels. “A healthy lifestyle is key in the prevention of the development of abnormal lipid and lipoprotein concentrations,” they claimed. They then admitted that dietary changes and increasing physical activity will result in modest changes to cholesterol levels, but asserted, with no evidence, that it will mean fewer children will go on to develop high cholesterol.
Did you just catch the bait and switch, again? True hypercholesterolemia is genetic and exceedingly rare, and population-wide interventions won’t prevent it. Neither will all of those obesity programs addressing healthy eating and exercise. But calling for such population-wide interventions adds to popular misperceptions and worries that everyone is at risk for true high cholesterol... and that healthy lifestyles can prevent it.
Actual high cholesterol is not caused by diets and it’s been recognized for decades that dietary cholesterol has little effect on serum cholesterol among most everyone else. Eat less cholesterol in foods and our livers naturally make more to try and maintain the range normal for each body. In fact, even the AAP authors noted the minimal reductions achieved by nonpharmacological interventions, such as dietary fiber and plant stanols and sterols, which block the absorption of cholesterol in food. The modest reductions (5-10%) won’t bring actual high cholesterols down to prescribed low levels, they said, while they raise important safety concerns through decreasing the absorption of fat-soluble vitamins and beta-carotene.
If it doesn’t work, start younger
One of the most controversial, and potentially most harmful, recommendations in this report is to lower dietary fat in all children beginning at 12 months of age with low-fat milk, and reduced-fat diets to manage weight for all children from the age of two. They claimed that these dietary changes could be safe and effective for lowering cholesterol levels.
But, as the USPSTF found after examining 81 quality clinical studies on cholesterol management: “There is no evidence that diet or exercise interventions in childhood lead to improved lipid profiles or better health outcomes in adulthood.” In fact, even the most rigorously followed low-fat, cholesterol-lowering diets, followed for more than 7 years, affects cholesterol levels little at all. The DISC study, for example, found no difference in total, LDL- or HDL-cholesterol levels among the kids after 5 and 7 years. The researchers observed that pubertal changes have the strongest impact on blood lipids and “sexual maturation had a stronger effect than diet.” Just as in adults, getting lipid levels down to the AHA’s recommended new low “ideal” levels cannot be achieved through diet and exercise — it means a lifetime of prescription medications.
More worrisome, dietary interventions are not benign. The USPSTF’s review of the body of evidence found that low-fat diets, most popularly referred to as “healthy eating,” not only lack evidence of effectiveness in reducing obesity, cholesterol levels or risks for heart disease, but they found evidence to suggest harm for children and teens, who need fats. [See “Low fat is not for kids” for more information.] And there is even less support, and greater dangers, for lowering fats in the diets of infants and toddlers.
The AAP authors went on to write that even higher levels of intervention are required for children with heterozygous familial hypercholesterolemia. They said interventions should initially focus on dietary changes. For children in the high-risk group, the AAP authors called for diets restricting saturated fats to 7% of calories and dietary cholesterol to 200 mg/day and that this is safe beginning at 7 months of age. To implement such aggressive diets would require the assistance of professionals to help the entire family “maintain a healthful diet and... navigate the food environment outside the home,” they said. A terrifying thought is how many parents of normal healthy babies and children will misread these interventions for heterozygous FH and wrongly believe they refer to their kids, and that more extreme dietary restrictions will provide even greater protection for their little ones.
Yet, in another head-spinning admission, the AAP authors said that for children with true high total and LDL-cholesterol levels, which have a genetic cause, “it is unlikely that diet alone will achieve appropriate concentrations of LDL.” This takes us to their ultimate recommendation: “But if this approach does not lower LDL to an acceptable concentration [which they just admitted it won’t], these children may be candidates for pharmacologic intervention.”
Backdoor to sell obesity programs?
The AAP recommendations appear less about actually addressing cholesterol and true hypercholesterolemia, and more about promoting anti-obesity interventions and weight management, while widening the market for prescription drugs. This new clinical guideline focuses on fat kids, advising:
For pediatric patients who are overweight or obese and have a high triglyceride concentration or low HDL concentration, weight management is the primary treatment, which includes improvement of diet with nutritional counseling and increased physical activity to produce improved energy balance.
But, again, true hypercholesterolemia, actually associated with greater risks for developing cardiovascular disease, isn’t caused by obesity, diet or exercise. Given the recent chastising the AAP received from the USPSTF for its previous unsound childhood obesity recommendations, it makes one wonder if these new guidelines are just a way to instigate them by creating a new medical imperative.
As readers may remember when the U.S. Preventive Services Task Force released its latest findings and summary of the evidence on childhood obesity interventions and screenings last year, its childhood obesity expert working group took an unprecedented step. It published a separate paper — titled “Screening for Overweight in Children and Adolescents: Where Is the Evidence?”— issuing a stern castigation to the American Academy of Pediatrics, American Academy of Family Physicians and other trade groups for supporting screening and interventions for childhood obesity, which lack any quality evidence, while putting children at risk.
The USPSTF group pointedly said that it didn’t matter how popular the practice might be among experts or how many endorsed it. Instead, it said the USPSTF “adheres strongly to a policy of making recommendations only in the presence of sufficient evidence of adequate quality... even for a practice that may be supported by expert consensus or less rigorous evidence.” Using strong language, it described the pervasiveness of those not understanding the potential harms of childhood obesity initiatives, admonishing: “The first principle of medicine is well known: primum non nocere (first, do no harm).”
After methodically reviewing 40 years of evidence — including about 6,900 studies and abstracts — the USPSTF found no credible evidence for screening for overweight in children and teens as a means to prevent obesity or adverse health outcomes; no quality evidence that diet and behavioral interventions for childhood obesity measurably improve children’s health outcomes or physiological measures, including blood lipids, glucose tolerance, blood pressure or physical fitness; and no credible evidence to support the effectiveness of any weight loss intervention, including lifestyle, diet, medications or bariatric surgeries.
Or increasing the market for statins?
The section of the new AAP guidelines that has received the greatest backlash is the section on pharmacological intervention. It recommended prescription drugs for children beginning at the age of 8.
Prior to age 8, the AAP authors recommended pharmaceuticals only for dramatic LDL-cholesterol levels greater than 500mg/dl, as seen in the rare homozygous FH.
But from then on, they skipped forward to recommending pharmacological treatment for children based on their new arbitrary cut-off points — which are within the ranges found in normal, healthy children and teens.
They justified earlier drug treatment beginning in childhood, saying: “It is not known whether there is an age at which development of the atherosclerotic process is accelerated.” Ignoring all of the evidence that body fat itself is unrelated to atherosclerosis, they claimed that the recent epidemic of childhood obesity would probably show more aggressive atherosclerotic processes among today’s children, requiring earlier interventions. They provided no evidence for these assertions.
They went on to write:
It is difficult to develop an evidence-based approach for the specific age at which pharmacologic treatment should be implemented. At the time of the NCEP [National Cholesterol Education Program] report, there were few studies of pharmacologic intervention in children, and the degree to which such therapy would produce important adverse effects was not known. More recent studies of children and adolescents have established the effectiveness and safety of the available agents, including their use in prepubertal children and children between 8 and 10 years of age.
In describing the various prescription medications available, they led up to statins as being the best option. As the AAP authors wrote, bile acid-binding resins are difficult to take and have gastrointestinal side effects that limit their use in young people. Compliance is also low. Niacin similarly has adverse effects that make it very difficult to use in pediatric clinical practice and “not recommended for routine use in the treatment of pediatric dsylipidemia.” Fibrates for treating elevated triglyceride levels has not been extensively studied in children and should be used cautiously, they said, especially in combination with statins or in patients with renal insufficiency.
Which brought readers to statins (3-Hydroxy-3-methyl-glutaryl Coenzyme A Reductase Inhibitors), which they claimed are well tolerated and result in cholesterol lowering of 20-50% depending on the dose used. They said there have been a number of clinical trials of statins in children and adolescents which, while short-term, have shown statins to be safe and effective in lowering cholesterol. Dr. Daniels and colleagues referenced a handful of studies to support this claim.
Their definitions for “safe” and “effective,” however, may be very different from yours’.
Effectiveness was based on surrogate endpoints, not clinical outcomes. While statins might be effective for lowering cholesterol to some degree, they haven’t been shown to offer any benefits in improving actual health outcomes for children. No studies have demonstrated effectiveness for the primary prevention of cardiovascular disease, either, which is the reason cited for starting them in kids. To date, statins have only been used in secondary prevention among middle-aged men with heart disease and, even then, the benefits in actual clinical outcomes have been nominal, with no benefit at all seen for women or the elderly. No statin has been shown to prevent heart disease.
Kids are decades away from having cardiovascular events. With no evidence that statins actually prevent adult cardiovascular disease, it makes the safety evidence for use in kids even more important. But how many practitioners will track down the studies the authors cited as evidence, to see that they actually found? Far from being “new”, the statin studies they referenced were 8 to 16 years old. Here’s a brief look:
de Jongh, et al., Circulation, 2002 — RCT of 173 children with heterozygous FH; 12-16 years old; 48 weeks; primary endpoints were cholesterol levels; no clinical outcome measures. Not sufficiently powered to evaluate side effects, but there were a total of 10 reported among the statin group and 4 among the placebo group for: chest pain, abdominal pain, sleep disorder, and increased lab values for ALT and AST. As the authors noted: “Thus far, there have only been a few studies evaluating statins in children, but these studies were either not randomized or controlled, they included only boys, they had a modest sample size, or they were of short duration... Data on growth and hormonal status indicated no significant differences between lovastatin and placebo in a 48-week time period. Although these studies showed good efficacy of statins in children, they were short-term, had a limited sample size, were mostly conducted in boys, or did not provide extensive information about growth and development.”
McCrindle, et al., Pediatr Res. 2002 — Randomized, open-label crossover trial with two 18-week medication regimens comparing bile acid-binding resin with statin; 36 children with FH; compliance was suboptimal at 60%; primary endpoint LDL-cholesterol level; no clinical outcomes; neither medication regimens lowered levels to recommended target values. The authors wrote: “Evidence of an effect of lipid lowering on vascular end points in children and adolescents is currently lacking... Studies of lipid-lowering pharmacologic therapy specifically in children and adolescents [show] the use of the bile acid– binding resins...although safe, is associated with only modest reductions in LDL cholesterol and poor acceptability and compliance... Studies with the statins... have been of relatively short-term duration. Experiences with other types of lipid-lowering drugs in children and adolescents have been limited, and there have been no studies of combination therapy... The general recommendation of the statins awaits long-term studies, evidence of alteration of the atherosclerotic disease process, and proof of cost-effectiveness in this population.”
Knipscheer, et al., Pediatr Res. 1996 — RCT of 72 children with heterozygous FH; 8-16 years of age; 8 weeks intervention in 4 different dose treatment arms; primary endpoints were cholesterol measures and hematological and biochemical lab values. These authors, from the University of Amsterdam, The Netherlands, were notable in their hesitancy to recommend statins for these children. They found that LDL cholesterol levels dropped below the 95th percentile in only a few children, the minimal level believed needed to slow down the atherosclerotic process in FH. “It is not yet known whether all subjects with FH need to be treated in childhood, to prevent premature CVD,” they wrote. “The necessity and benefit of lowering cholesterol in children with FH, is debated, and furthermore, treatment may be associated with unwanted side effects. Growth and maturation of (pre)-pubertal children could be negatively affected by modifying cholesterol synthesis. Moreover, results of recent trials suggest that, when treatment is postponed until adulthood, progression of atherosclerotic lesions can still be influenced... At the present time, the recommended therapeutic regimen for children with FH is restricted to bile acid binding resins in conjunction with a lipid-lowering diet. Long-term studies, however, reported modest reductions of approximately 12% of plasma total cholesterol with this regimen... and essentially insufficient to modify the process of vessel wall damage... only a few small observational studies, concerning the use of these drugs in children, have been reported.” They said that internationally, long term experience with this regimen is “very disappointing with respect to effective cholesterol lowering.”
They concluded: “Cholesterol-lowering treatment with pravastatin is safe, well tolerated, and effective in children with FH. However, before new treatment strategies in these children are to be considered, results of long-term studies have to be awaited.” A special addendum was added to this study that bears note: “After acceptance of this manuscript we became aware of an independently performed study in which three statins (simva-, lova- and pravastatin) were compared in young rats. Clinical signs (myopathy, walking, body weight), plasma creatine kinase activity (as a measure of muscle damage), and histologic validation of muscle damage were used as parameters. It appeared that the lipophilic statins (simva- and lovastatin) caused a strong reduction in body weight, very high plasma creatine kinase activity, and myopathy, in a dose-dependent fashion. Simvastatin was most potent in this respect, whereas lovastatin produced these effects at higher doses...”
Lambert, et al., Pediatrics. 1996 — RCT of 69 boys with familial FH; ages 10-15 years; 8 weeks; primary outcome measures only changes cholesterol levels; no clinical outcomes. Reported no serious adverse reactions.
Stein, et al., JAMA. 1999 — RCT of 132, 122, and 110 boys with heterozygous FH; ages 10-17 years; conducted in 1990 and 1997; one-year 2-arm design; primary outcome measures only changes in LDL-cholesterol levels; no clinical outcomes. Growth and sexual maturation was assessed at 48 weeks and not significantly different, but the study was underpowered to detect significant difference in safety parameters.
McCrindle, et al., J Pediatr. 2003 — RCT of 187 children with FH; average age 12-16 years; 26 weeks cross-over design; primary outcome measures only changes in lipid measurements; no clinical outcomes. The authors emphasized that this study was of FH, a rare mutation characterized by exceedingly high cholesterol levels, with LDL-cholesterols alone 230-500 mg/dl. This disorder is so rare this study had to be conducted at 20 centers around the world to find even 187 children with the condition. Still, the study didn’t include enough kids in each arm to be sufficiently powered to evaluate the significance of the adverse effects. The intervention groups, however, did report 45% higher rates of flu-like symptoms, abdominal pain, headaches, infections and more than twice the rates for accidental injuries. One child had to be withdrawn for severe depression, judged as possibly treatment related.
Just as the USPSTF and other objective reviews have found worrisome about the statin research in young people to date, the studies are all short-term and on small numbers of children, all of whom had the rare genetic disorder FH. No one knows what the risks are for young people taking these drugs for decades. The most glaring deficiency in the AAP’s clinical guidelines is that the authors failed to weigh the possible risks of putting vast numbers of healthy children on statins for the rest of their lives.
Statins’ actions aren’t yet fully understood, even in adults, but their side effects are increasingly being recognized. Myopathy and myalgia among statin users, for example, weren’t always recognized as being related to the statins. To put the pieces together and attempt to quantify the risks among adult statin users, researchers in London compiled the medical records for 93,831 patients on statins for 12 and 26 weeks, to look for correlations with diagnosed myopathy. Their results were just published. They found that, depending on the statin, the relative risks for myopathy associated with statins were as high as 40.5 times (RR=40.5), with all classes associated with an average risk of 10.6 times as high. Those are relative risks worthy of sitting up and taking notice.
The pediatric statin studies cited, though, didn’t evaluate the most serious complications being seen among adults. For example, while several of these studies reported children complaining of muscle and abdominal pain, none of the young people were evaluated for myopathy or rhabdomyolysis; none of their higher rates of flu-like symptoms were evaluated for effects on their immune system, which could have serious long-term effects from infections to cancers; neurological and vision effects weren’t evaluated, even though they reported headaches, accidents and depression at higher rates; none of the children were evaluated for cognitive effects on learning and memory. Given the special risks documented in seniors on statins, Dr. Beatrice A. Golomb, M.D., Ph.D., said special caution is warranted for the long-term use of statins in pediatric populations.
And, of course, one of the most immediately frightening risks are those for young women who become pregnant while on statins and their babies, or the unknown effects on their fetus’ after the girls have taken statins for years to decades.
Warning for parents about statins in kids
The FDA has not approved statins for the primary prevention of heart disease in children. Yet, the AAP authors are recommending statins in pediatric age groups for uses these drugs have not been approved.
As the USPSTF experts emphasized, “drug treatments for dyslipidemia in children have been studied only in children with FH or familial combined hyperlipidemia, the population for whom these drugs are Food and Drug Administration–approved.” Cholesterol lowering drugs are not approved by the FDA for other uses in children. Nor is it known how their effects in these rare, extreme conditions “translate to children with milder and/or nonmonogenic dyslipidemia.”
Looking at the statin information at the FDA Center for Drug Evaluation and Research reveals that the safety and effectiveness for statins have not been established in pediatric patients and their use is not recommended. For example:
Simvastatin (Zocor) — Safety and effectiveness in pediatric patients have not been established. Because pediatric patients are not likely to benefit from cholesterol lowering for at least a decade and because experience with this drug is limited (no studies in subjects below the age of 20 years), treatment of pediatric patients with Zocor is not recommended at this time.
Atorvastatin (Lipitor) — Lipitor has not been studies in controlled clinical trials in prepubertal patients or those younger than 10. Doses greater than 20 mg have not been studied in this patient population.
Rosuvastatin (Crestor) — Safety and effectiveness in pediatric patients have not been established. Treatment experience is limited to 8 patients with homozygous FT, none under age 8.
Lovastatin (Mevacor) — Safety and effectiveness in pediatric patients have not been established. Because pediatric patients are not likely to benefit from cholesterol lowering for at least a decade and because experience with this drug is limited (no studies in subjects below the age of 20 years), treatment of pediatric patients with lovastatin is not recommended at this time.
Behind the scenes — what you may not know
These clinical guidelines were not developed, reviewed or voted on by the membership of the American Academy of Pediatrics before being issued.
At its October 2001 meeting, the Board of Directors of the Academy changed its procedure for how policy statements, clinical practice guidelines, technical reports, and various official statements are developed — to make the process more “organized and efficient.” Now, they are written by an entity within the Academy, such as a committee, and then only need to be approved by the AAP Executive Committee before being issued in Pediatrics as official AAP policy.
These new lipid guidelines were written by its Committee on Nutrition with Dr. Stephen R. Daniels, M.D., as the lead author.
Whenever we hear conclusions and recommendations that are so diametrically opposed to the evidence and filled with so many pop beliefs, as in these guidelines, it can be valuable to inquire if there might be potential conflicts of interest which may have influenced the author. There was no disclosure statement in the Pediatrics article. But that isn’t the full story.
Dr. Daniels is professor and associate chairman of the Department of Pediatrics at Cincinnati Children's Hospital. He is the medical director of Healthworks, its pediatric weight loss program that’s based on diet and exercise interventions, and which includes comprehensive clinical workups through its Cardiac Clinical Care Program. He also directs the pediatric lipid, hypertension and weight management clinics at Cincinnati Children's Hospital.
Besides a career invested in childhood obesity and management of metabolic risk factors, he has also been active politically in these arenas. For example, he was a key speaker and participant in the well-publicized Time Magazine/ABC News Summit on Obesity in 2004, sponsored by the Robert Wood Johnson Foundation, which heavily promoted a national obesity epidemic, along with their solutions. He authored the 2006 paper on the “Consequences of childhood overweight and obesity” for The Future of Children at Princeton University and The Brookings Institution. It described the “heavy toll that the obesity epidemic” is taking which, he predicted, will lead today’s youth to live “ultimately shorter lives than their parents, the first such reversal in lifespan in modern history.” That makes childhood obesity an issue of “utmost public health concern,” he wrote. A major consequence of childhood obesity, he asserted, was the constellation of health risk factors called metabolic syndrome. This paper is strikingly similar to the claims made in the AAP paper he authored.
Dr. Daniels has also been active in writing a number of clinical guidelines. He served as a member of the Pediatric Working Group of the National High Blood Pressure Education Program and was in the Writing Group for the American Heart Association – NHLBI 2005 Scientific Statement on the Diagnosis and Management of the Metabolic Syndrome. Dr. Daniel’s disclosures in its Disclosure Statements stated he has received Research Grants from:
· Pfizer [whose U.S. sales of Lipitor, in 2007 alone, topped $12.7 Billion]
· Inamed, now Allergan [the Lap-Band bariatric surgical device maker]
Dr. Daniels also disclosed being a Consultant/Advisory Board for:
· Merck & Co. [the maker of Zocor, which has been issued multiple FDA warning letters for fraudulent claims, but generates about $4 billion in annual U.S. sales for the company; and the maker of Mevacor, which the company (with J&J and GlaxoSmithKline), tried three times, unsuccessfully, to win approval from the FDA to sell it OTC after its patent ran out in 2001]
He was also in the Writing Group for the American Heart Association 2007 Scientific Statement,Drug Therapy of High-Risk Lipid Abnormalities in Children and Adolescents, which concluded that lifestyle recommendations were ineffective in reducing high lipid abnormalities in children and teens and they “will require lipid-lowering drug therapy.” In its Disclosure Statement, the lead author, Brian W. McCrindle made financial disclosures to four pharmaceutical companies and Dr. Daniels made an additional disclosure of Research Grant money from:
Clinical care guidelines affect the quality of care and lives of every patient and family in the country. People deserve care that is based on sound information and careful, objective evaluations of the best evidence, with proven benefits that outweigh the potential harms to them. Healthcare should be about health, not politics, profits or prejudices. Pediatric patients lost out in these.
© 2008 Sandy Szwarc