An estimated one in 250 U.S. adults have familial hypercholesterolemia, according to an analysis of the 1999 to 2012 National Health and Nutrition Examination Survey (NHANES).

The researchers mentioned the estimate was higher than the commonly reported prevalence of 1 in 500 adults but lower than the prevalence recently reported in Europe.

Lead researcher Sarah D. de Ferranti, MD, MPH, of Boston Children’s Hospital, and colleagues published their results online in Circulation on March 14.

They defined familial hypercholesterolemia as a genetic disorder that causes severely elevated low-density lipoprotein (LDL) cholesterol. If left untreated, familial hypercholesterolemia is associated with an approximate 90-fold increase in atherosclerotic cardiovascular disease (ASCVD) mortality among young adults, according to the researchers. However, they noted that statins could reduce the risk of ASCVD.

For this analysis, the researchers used the modified version of the Dutch Lipid Clinic criteria, which classifies familial hypercholesterolemia based on LDL cholesterol, physical examination findings, genetic criteria and personal and family history of premature ASCVD.

They analyzed data on 36,949 adults who were at least 20 years old and participated in NHANES, which are nationally representative surveys of the U.S. population. Participants were excluded if they were pregnant.

More than 50 percent of participants with familial hypercholesterolemia had high rates of personal or family history of early ASCVD events. Indicators for early ASCVD include coronary heart disease, angina, MI or stroke at 55 years old or younger in men and 60 years old or younger in women. They defined a family history of early ASCVD as having a parent or sibling with heart disease or angina at younger than 50 years old.

The overall prevalence of probable or definite familial hypercholesterolemia among NHANES participants was 1 in 250 or 0.4 percent. The researchers said probable familial hypercholesterolemia affected an estimated 0.38 percent of participants, while definite familial hypercholesterolemia affected an estimated 0.02 percent of participants.

After extrapolating those figures to the general U.S. population, an estimated 834,500 U.S. adults had probable or definite familial hypercholesterolemia.

The researchers estimated that 0.58 percent of obese and 0.31 percent of nonobese adults had familial hypercholesterolemia. They defined obesity as a body mass index of 30 kg/m² or higher.

Further, the prevalence of familial hypercholesterolemia was highest among whites, blacks and other Hispanics (ranging from 0.40 percent to 0.58 percent) and lowest among Mexican Americans and other races (ranging from 0.24 percent to 0.29 percent).

A secondary analysis of 13,343 adolescents found the prevalence of familial hypercholesterolemia among participants between 12 and 17 years old was 0.42 percent or 1 in 237 adolescents. The researchers mentioned the adolescent familial hypercholesterolemia prevalence estimate was based only on LDL cholesterol levels because NHANES did not include relevant family history among participants who were younger than 20 years old.

“Whereas our adolescent [familial hypercholesterolemia] prevalence estimate aligns well with the overall U.S. population estimate, it should be interpreted with caution,” they wrote. “The adolescent NHANES sample is smaller, and lipid levels differ by sex and change with pubertal stage, also contributing to uncertainty in this pooled analysis.”

The researchers mentioned the main analysis among adults had limitations, as well, including that participants self-reported their ASCVD events and family history.

“Further investigation into the prevalence of [familial hypercholesterolemia], including diverse and pediatric populations and the use of genotype along with phenotype, will improve our understanding of the national burden of [familial hypercholesterolemia], an important cause of ASCVD,” they wrote.