EDITORIAL Familial Hypercholesterolemia—We Must Act Boldly

I just recently returned from the national lipid meetings and was impressed with the information presented about familial hypercholesterolemia, both in the homozygous and heterozygous form. It is clear from a recent article published by Nordestgaard in the European Heart Journal I 2013 that heterozygous familial hypercholesterolemia is underdiagnosed and undertreated. It may be seen in as many as 1 in 200 patients in the Netherlands. Homozygous, hypercholesterolemia may occur more than the usually quoted 1:1 000 000 patients as well. It is my feeling that unless we do universal screening, we will never identify the probands with both homozygous and heterozygous familial hypercholesterolemia. Currently, there is advocacy for cascade screening, but I do not think cascade screening can be effectively done unless you have got the original patients that you have identified through some other form of screening process, and I think that other form of screening process is universal screening. I do not think cascade screening is an effective broad spectrum screening tool. It certainly can be effective once the individuals are identified and should be done, but we must think about universal screening to identify all the homozygous and heterozygous patients. Until statins were developed, the treatment of children with homozygous or heterozygous was very frustrating. Resin therapy was just not well tolerated by children, and as many as 80–90% had stopped taking their cholestyramine or colestipol within a year of diagnosis and treatment. In pediatrics, statins provided us a treatment regimen that was well tolerated and, based on ongoing studies, is quite safe throughout childhood. The problem is that statins and other forms of therapy almost never get the cholesterol levels back to normal. If a child starts out with a cholesterol of 700 or 800 and that is reduced by half to 300–400, I am not sure that really makes a major difference in the long-term outlook of that child as it relates to the development of atherosclerosis. People are currently excited about LDL apheresis, © 2014 Wiley Periodicals, Inc.

but I do not see that as an end-stage therapy, particularly for children. For a child and a family to have to come in every 2 weeks and to have apheresis is more burdensome and more difficult than dialysis, and most families after a short period of time find it very difficult to continue with this therapy. I am also not sure that the wide fluctuations in LDL and total cholesterol levels that occur on apheresis when for a short period of time the lipids will be normal but then within weeks they bounce back to very high levels are very good. We have certainly seen with diabetics that poor glucose with fluctuating levels is not good for the health of the patients, and these fluctuating levels of normal vs. very high levels of cholesterol intuitively might also not be very good. I think because of the concern of never having the lipids get back to normal, even on medical therapy, we must boldly think about treating patients with homozygous cholesterolemia, particularly those families when there has been a history of myocardial infarction and death in the teens, 20s, and early 30s. We are about ready to report our experience in a small group of children who have undergone liver transplant for homozygous hypercholesterolemia. We have been very pleased that the lipids have normalized, and in fact, we have seen aortic and arterial calcification disappear following liver transplant. There is no question that liver transplant is a major step in a child with this condition, but the outlook in some of these families is so poor, and the ability to really manage the cholesterol can be so difficult that one needs to give consideration early on to liver transplantation in these most severe and difficult cases. I am hopeful that with our soon-to-be-published article, others will report of their limited experience with liver transplantation as I think this is a modality that will need to be considered more strongly in the future. We still do not know when children with homozygous or even heterozygous hypercholesterolemia actually develop coronary disease. It does appear that this probably occurs in the teens but that has not been totally well defined, Congenit Heart Dis. 2014;9:273–274

274 and so, we must be sure before we undergo liver transplantation that the coronaries are normal. Thus, with all aspects of homozygous and heterozygous hypercholesterolemia, we must act boldly. I think we should be doing universal screening in these patients and then perform cascade screenings on the families. I think some children will benefit over a very short time with LDL apheresis, but that is not a destination therapy and is a therapy that needs to be utilized on the way to planning for liver transplant. We and others have seen that liver transplant can be very effective, but it is a bold step and one that must be considered carefully and cautiously. However, the early results are exciting, and given some of the

Congenit Heart Dis. 2014;9:273–274

Editorial severe family histories and early death from coronary disease, it is a consideration that should be entertained more frequently in the management of these patients. For familial homozygous hypercholesterolemia, to ensure the best outcome for our patients, we must act boldly. Douglas Moodie, MD, MS Associate Chief, Pediatric Cardiology Director, Pediatric Cardiology Fellowship Program Associate Director, Adult Congenital Heart Center, Professor of Pediatric Cardiology, Baylor College of Medicine, Texas Children’s Hospital, 6621 Fannin Street MC, 19345-C, Houston, Texas 77030, USA

Familial hypercholesterolemia--we must act boldly.

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