July 08, 2008
Fat Kids? Feed 'em Statins and Supplements
The American Academy of Pediatricians provoked an instantaneous uproar yesterday after releasing new guidelines calling for screening kids for high cholesterol and prescribing statin drugs if diet and exercise interventions don't work. The New York Times' Tara Parker-Pope was forced to print a reaction story today that included all the critical comments left out of the previous day's report.
“What are the data that show this is helpful preventing heart attacks?” asked Dr. Darshak Sanghavi, a pediatric cardiologist and assistant professor at the University of Massachusetts Medical School. “How many heart attacks do we hope to prevent this way? There’s no data regarding that.”Nor, Dr. Sanghavi added, are there data on the possible side effects of taking statins for 40 or 50 years.
Other doctors said the recommendation would distract from common-sense changes in diet and exercise, which are also part of the new guidelines.
“To be frank, I’m embarrassed for the A.A.P. today,” said Dr. Lawrence Rosen of Hackensack University Medical Center in New Jersey, vice chairman of an academy panel on traditional and alternative medicine. He added: “Treatment with medications in the absence of any clear data? I hope they’re ready for the public backlash.”
How hard would it have been to include those perspectives in the original story?
Here's something else that was left out of all the stories. A lot of bloggers, and even Parker-Pope in today's story, focused on possible financial ties to statin manufacturers of the seven physicians who wrote the guidelines for the AAP. I briefly checked out that possibility yesterday since the AAP in-house journal Pediatrics, which published the guidelines, failed to include a conflict of interest disclosure statement even though the journal has a policy requiring such statements.
I didn't come up with much on statins. But Jatinder Bhatia, who sat on the committee and was prominently quoted by Parker-Pope in her first story, has disclosed elsewhere that he is consultant and speaker for Mead Johnson, a unit of Bristol Myers-Squibb best known for its line of infant formulas (Enfamil). It also makes supplement-enhanced foods aimed at young kids. The AAP itself has numerous financial ties to manufacturers of enhanced foods.
Is that relevant? Should it have been disclosed? Here's a couple of other lines from the guidelines:
Increasing the intake of soluble fiber can be helpful in reducing plasma LDL concentration. . .Plant stanols and sterols are added to a number of products, including spreads and margarine, orange juice, yogurt drinks, cereal bars, and dietary supplements. These compounds lower the absorption of dietary cholesterol and, in adults, have been shown to reduce cholesterol concentration by approximately 5% to 10% with minimal adverse effects.
Mead Johnson makes kid foods with added fiber. Yoplait markets a line of "heart healthy" yogurts. I don't know if Dannon does, but that firm is clearly a competitor of Yoplait. Besides Bhatia's ties to Mead Johnson, Nicolas Stettler, another panel member, sits on the board of the Dannon Institute, a non-profit research wholly funded and housed within the Dannon Yogurt Co.
While everyone is focused on the statin angle, the subtext here may be functional foods. Ads touting "heart healthy" brands for fat kids -- now recommended by the nation's pediatricians -- may be just around the corner.
Just what they need. More food advertising.
Posted by gooznews at July 8, 2008 08:20 AMI have some thoughts on the AAP guidelines, but in the interest of full disclosure, I want to first state that my 15-year-old daughter is on 20 mg. atorvastatin (Lipitor). She has a genetic disorder called heterozygous familial hypercholesterolemia (heFH), which occurs in approximately 1/500 people. HeFH causes very high LDL levels from birth (approximately 250 in my daughter's case) and cannot be controlled with diet and exercise. It causes premature heart disease in most cases if not treated. People with heFH must be treated with statins, although the best age to start is not known (and may never be known). When statins were introduced, no placebo-controlled trials were conducted in heFH patients because it was thought to be unethical. However, observational data indicate that statins dramatically lower cardiovascular morbidity and mortality in heFH patients.
Imaging studies of kids with heFH have shown that they have increased carotid intima-media thickness (IMT) by age 12 compared to their unaffected siblings. A number of randomized placebo-controlled trials of statins have been done in kids with heFH. Some of these just looked at lipids and safety, but at least one used IMT as an endpoint and showed a benefit for the statin group. Statins also improve endothelial function in kids with heFH. The proposed expansion of statin use builds on this experience with heFH children.
Is the use of statins in kids heFH evidence-based? In the sense of having definitive proof that it prevents heart attacks, no. Kids don't have heart attacks normally, so you cannot conduct a trial with clinical endpoints in kids. What we have is (1) as mentioned above, evidence that statins slow or prevent atherosclerosis in kids with heFH, and (2) evidence that statins prevent heart attacks and strokes in adults. Even if treating kids were known to prevent heart attacks, one could then ask whether it prevents more heart attacks than treating starting at age 18, 20 or later. We don't know the answer to that either. However, because of the very high risk associated with LDL levels in the 200s and 300s, it can be argued that starting treatment early is not unreasonable in kids with heFH, especially boys.
The expansion of guideline recommendations, including the AAP guidelines and the American Heart Association guidelines for drug therapy for children and adolescents with high-risk lipid abnormalities (published in Circulation in 3/07) build on the experience in treating kids with heFH. The two sets of guidelines are similar in most respects, with this notable difference: the AHA guidelines recommend using statins as first-line therapy. The AAP guidelines simply recommend "pharmacologic intervention," leaving the choice of drug up to the individual prescriber.
I view both sets of guidelines as overly aggressive, given the uncertain risks and benefits involved. Obviously I am not against treating very high risk kids or my daughter would not be on a statin. I'm sure that there are a small number of kids (other than kids with FH) where a low or moderate dose of a statin could be considered. Even in those cases, however, I view the LDL targets advocated in the AAP and AHA guidelines as being arbitrary. We have no data showing that kids with a certain number of risk factors should have an LDL target of 160 or 130 or 110.
In addition, I think any kids who are treated should be treated with a statin. The AAP guidelines state that ezetimibe (Zetia) is a "potentially important first-line treatment for children," but ezetimibe has not been shown to prevent heart attacks and strokes in adults and in the ENHANCE trial it added no benefit to simvastatin in reducing IMT progression. I do not believe it is appropriate to use ezetimibe in kids. I am also uncomfortable with the idea of using bile acid sequestrants and fibrates.
None of the cholesterol drugs are approved for use during pregnancy. Therefore, I do not believe they should be prescribed to teenage girls except those who are very high risk, and the girls should be counseled to avoid pregnancy.
I share Merrill's discomfort with foods containing plant sterols or stanols. There have been no clinical trials showing that supplementing the diet with foods containing plant sterols or stanols prevents cardiovascular disease. Ingesting plant sterols causes an increase in serum levels of plant sterols. Whether this is safe or not is not known.
Marilyn
Posted by: Marilyn Mann at July 8, 2008 10:38 PMThank you, Merrill, for writing about this. Marilyn, I really appreciated your insightful comments as well.
(Incidentally, I know someone with HeFH who has controlled it with diet alone. It is one case, but she says she consulted with a physician who has treated many with diet alone. It's a strict diet, however.)
Posted by: Christe at July 9, 2008 01:06 AMChriste,
Has your friend been tested for a heFH mutation? In other words, is she sure she has heFH? It is possible to lower LDL levels with diet, but usually only to a minor extent. Usually, heFH patients need to decrease their LDL 50% or more to reach normal levels. I have never heard of someone achieving that with dietary changes.
Marilyn
Posted by: Marilyn Mann at July 9, 2008 04:46 AMI would like to provide some references and suggested background reading on this topic.
I was surprised that the press reports on the AAP guidelines did not mention the AHA guidelines. McCrindle, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing. Circulation. 2007;115(14):1948-1967.
http://www.circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.181946v1
Although I do not endorse all the recommendations in the AHA guidelines, I view them as superior to the AAP guidelines. They are somewhat less aggressive than the AAP guidelines in that they state that "the age and LDL level at which statin therapy is initiated may be influenced by the presence, magnitude, and number of other cardiovascular risk factors, as well as by the presence of cutaneous xanthomas," and "[i]n general, do not start before 10 years of age in boys and preferably after onset of menses in girls." The AHA guidelines recommend statins as first-line therapy, and state that "[i]t is likely that ezetimibe will be used predominately in children with persistent elevations of LDL cholesterol after treatment with other drugs."
An interesting study published in the NEJM showed that people who have a mutation that causes lifelong low LDL levels have a much lower incidence of heart disease than the general population. Cohen et al., Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease. NEJM. 2006;354:1264-1272.
http://content.nejm.org/cgi/content/abstract/354/12/1264
Rodenburg, et al., Statin treatment in children with familial hypercholesterolemia: the younger the better, Circulation. 2007;116:664-668.
http://www.circ.ahajournals.org/cgi/reprint/116/6/664
Weingartner, et al., Vascular effects of diet supplementation with plant sterols, J Am Coll Cardiol, 2008; 51:1553-1561. http://content.onlinejacc.org/cgi/content/abstract/51/16/1553
Helske, et al., Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves. Journal of Lipid Research, Vol. 49, 1511-1518, July 2008.
http://www.jlr.org/cgi/content/abstract/49/7/1511
Jessup, et al., Phytosterols in cardiovascular disease: innocuous dietary components, or accelerators of atherosclerosis? Future Lipidology. June 2008, Vol. 3, No. 3, Pages 301-310.
http://www.futuremedicine.com/doi/abs/10.2217/17460875.3.3.301
Allen Taylor, Given the ENHANCE trial results, ezetimibe is still unproven, July 2008 Cleveland Clinic Journal of Medicine.
http://www.ccjm.org/ccjm_pdfs_toc/July08_Taylor.pdf
Kastelein, et al., Simvastatin with or without ezetimibe in familial hypercholesterolemia. NEJM. 2008;358:1431-1443.
http://content.nejm.org/cgi/content/short/358/14/1431
The US bear market has affected dozens of companies, many in the financial sector. US consumers have seen their disposable income decreased substantially and they are unable to refinance their homes to get some needed relief as the mortgage market has tightened. Inflation with respect to energy has really hurt commuters as we have seen gas prices shoot through the roof, and they have had no other option but to trade in their SUVs and squeeze their two kids and family dog into a Prius.
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