People with a rare genetic condition that causes extremely high levels of Low-density lipoprotein cholesterol LDL-C may miss decades of treatment due to a lack of childhood lipid screening, researchers reported at the 2022 annual meeting of the American Academy of Pediatrics (AAP).
The researchers said routine screening for FH is uncommon. Unfamiliarity with the guidelines and limited access to lipid specialists cited Possible causes for inconsistent screening practices.
These recent findings and improvements in lipid-lowering therapies make a compelling case for their strict compliance AAP Guidelines About lipid screening for children with a family history of FH or ASCVD at age 2,” said study co-author Mary P. statement about the new study.
To characterize patients with homozygous FH, McGowan and colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation Establishing the registry in 2013, 40 medical centers in the United States contribute data to the repository. The researchers had access to data on patients with homozygous FH from 20 centers on the registry.
McGowan’s group compared 16 homozygous FH patients who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.
The mean age at diagnosis for patients enrolled as children was 2 years (interquartile range [IQR]2 – 3.5), while the mean age at diagnosis for patients registered as adults was 12.6 years (IQR, 4.1 – 26.5).
The mean level of untreated LDL-C in children enrolled in the pediatric population was 776 mg/dL (IQR, 704 – 892). Among those enrolled as adults, the ratio was 533 mg/dL (IQR 467–702).
Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The mean age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at 2 years of age and underwent it Liver transplantation At the age of 4 years. Another was diagnosed at the age of 3 years and underwent a liver transplant at the age of 8 years. Two children underwent coronary artery bypass grafting at 6 and 14 years of age. Five participants underwent a liver transplant before the age of 18 years.
About 56% of the participants who were enrolled in childhood had xanthoma, or fatty deposits in their tendons, and none had a corneal arch – a gray-white line of fat deposits around the edge of the cornea, both of which could indicate homozygous in children.
The treatment lowered LDL-C significantly, but only 25% of the children achieved target cholesterol levels, the researchers reported. They found that patients who received more lipid-lowering treatments had a better chance of reaching target levels.
The data raises “the possibility that children with the most severe phenotypes will only be diagnosed before adulthood,” the researchers said.
The researchers note that the clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthoma. Many children do not have physical findings, however, lipid screening or genetic testing may be necessary.
“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, McGowan said.
Possible missing cases
Up to 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to Estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, LDL-C levels are usually between 400 and 1000 mg/dL untreated, which is Four to ten times higher About normal concentrations of fats in the blood, according to the Family Heart Foundation.
“This study adds to a growing body of literature—including Our own business Evidence that the recommended “universal screening” occurs in barely one in five children. This means that some patients are not recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.
Even among children at risk for early adult-type heart disease, only a quarter to two-thirds of them receive the recommended screening, said Berger, who was not a member of the study team.
While Berger advocates universal lipid screening, improving screening rates in practice is probably not as simple as telling doctors to check more, he said. “Increased testing will increase healthcare spending and burden busy primary care providers without specifying who will subsequently evaluate and manage children with abnormal lipid screening results,” Berger said.
Instead, clinicians may want to focus on screening high-risk patients, which “could have significant benefits for lifelong cardiovascular health,” he said.
McGowan disclosed her relationships with Abbott and Regeneron, and her co-authors disclosed their relationships with Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Berger has not disclosed any relevant financial relationships.
American Academy of Pediatrics (AAP) National Conference 2022. Presented October 8, 2022.