US Prevalence of Familial Hypercholesterolemia Higher Than Expected

Pam Harrison

March 14, 2016

The prevalence of familial hypercholesterolemia (FH) in the US is twice that of previous estimates, although the likelihood of having the disorder to a large extent depends on ethnicity and age, suggests analysis of a nationally representative sample of US residents[1].

"There is a perception that FH is uncommon, that it's a rare genetic condition and can be easily appreciated by family or medical history. But in fact, many individuals present with early heart disease or death instead of FH being detected early enough to try to prevent the outcome," Dr Sarah de Ferranti (Boston Children's Hospital, MA) told heartwire from Medscape.

"So a better understanding that FH is a common disorder affecting many individuals in the US is needed," said de Ferranti, who is lead author on the study published March 14, 2016 in Circulation.

DLC Criteria

FH in the analysis was defined by applying a modified version of the Dutch Lipid Clinic (DLC) criteria to participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012. As the authors note, DLC criteria define "definite" or "probable" FH based on levels of LDL cholesterol as well as findings on physical examination, genetic criteria, and personal or family history of premature CAD, stroke, or peripheral vascular disease (PVD).

A total of 36,949 participants were included in the study. "The overall adult US prevalence of probable/definite FH in NHANES participants was 0.40%," they write, or a prevalence of one in 250. "Our estimate is higher than the commonly reported prevalence of one in 500, which originated in selected, nonrepresentative populations."

As expected, over 50% of individuals with FH had a personal or family history of early CAD, stroke, or PVD and 81% of them were receiving some form of lipid-lowering treatment.

DLC Criteria

FH in the analysis was defined by applying a modified version of the Dutch Lipid Clinic (DLC) criteria to participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012. As the authors note, DLC criteria define "definite" or "probable" FH based on levels of LDL cholesterol as well as findings on physical examination, genetic criteria, and personal or family history of premature CAD, stroke, or peripheral vascular disease (PVD).

"The overall adult US prevalence of probable/definite FH in NHANES participants was 0.40%," they write, or a prevalence of one in 250. "Our estimate is higher than the commonly reported prevalence of one in 500, which originated in selected, nonrepresentative populations."

Estimates of "probable" FH were much higher than estimates of "definite" FH, they add. Probable FH was felt to affect 0.38% of the US NHANES population, or one in 267 individuals, but definite FH was less prevalent at only 0.02% of the population, or one in 4023 adult participants.

Based on their findings, the investigators estimated that 834,500 adults in the US had probable or definite FH.

FH was least common in individuals between 20 to 29 years of age, affecting one in 1557 participants, compared with one in 118 individuals between the ages of 60 and 69 years. The prevalence was one in 249 for whites and one in 211 for African Americans. The prevalence of FH was highest in Hispanics, affecting one in 174 individuals, and lowest in Mexican Americans with a prevalence of one in 414.

The large variance in FH prevalence among different ethnic groups potentially explains the lower prevalence estimates made in the past compared with rates in less ethnically diverse populations, according to the authors.

FH Among Adolescents

The prevalence of FH in 12- to 17-year-olds was estimated at one in 237, the group reports, noting that the FH definition in that age group was based on LDL-C alone because family history was not collected in NHANES participants under the age of 20.

They also note that probable or definite FH was seen more commonly in the obese, at one in 172 adults, compared with the nonobese, in whom the estimate was one in 325 adults.

"The prevalence of FH in our estimates seemed to increase as people got older, but since this is a genetic disorder, FH should be present from birth," de Ferranti said. "So my suspicion is that our estimates might be further refined if we could get genetic testing data, which we did not have in this data set."

In fact, had investigators been able to include results of genetic testing, they speculate the prevalence of FH might have increased by as much as 25% over estimates from the current analysis.

"I'm not advocating genetic testing across the board," de Ferranti emphasized. "But we are beginning to think about patients in whom genetic testing might be helpful such as patients who might be borderline FH."

Diagnostic Complexity

In their accompanying editorial[2], Dr Anne Goldberg (Washington University School of Medicine, St Louis, MO) and Dr Samuel Gidding (DuPont Hospital for Children, Wilmington, DE) point out that there is a certain amount of diagnostic complexity behind FH, which depends on an individual patient's risk for vascular events, and as such, treatment may vary. For heterozygous FH patients, effective treatment might include both lifestyle modification and the use of a statin plus ezetimibe.

For severe heterozygous FH patients, additional therapies including LDL apheresis and the recently introduced proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may allow physicians to reduce LDL-cholesterol levels to an optimal target. "Long-term drug therapy has the potential to lower coronary heart disease event rates in FH patients to levels similar to those of the general population," the editorialists state.

de Ferranti receives royalties from UpToDate for review topics on cholesterol screening and treatment in childhood and serves on the American Academy of Pediatrics Committee on Nutrition and the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee. Disclosures for the coauthors are listed in the article. Goldberg receives consulting fees from Sanofi/Regeneron and OptumRx and research grant support from Amarin, Merck, ISIS, Sanofi, Regeneron, Amgen, Pfizer, Genentech/Roche, and GlaxoSmithKline and honoraria for editorial work on the Merck Manual. Gidding is a member of the scientific advisory board and publication committees of the FH Foundation. He has received honoraria from the American College of Cardiology for producing FH-related educational materials.

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