Prevalence Familial Hypercholesterolemia in US is higher than reported to date

Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES)

Literature - de Ferranti SD et al., Circulation. 2016

de Ferranti SD, Mae Rodday A, Mendelson MM, et al.
Circulation. 2016;133:1067-1072


The identification of familial hypercholesterolemia (FH) as early as possible in life is very important, because the natural course of this genetic disorder is associated with an approximate 90-fold increase in premature atherosclerotic CV disease (ASCVD) in young adults. This increase can be modified with the use of lipid-lowering therapy [1,2].
FH prevalence is estimated at 1 in 137 to 500, depending on ancestry and definition, and these numbers are mainly based on white European populations. The FH prevalence in the US is not known [3,4]. Extrapolating the European numbers to the US population does not reflect the racial and ethnical diversity in the US [5,6]. Knowing the proportion of the population affected by FH in the US is essential to understand the impact of this genetic disorder on US public health, and to properly guide FH screening.
In this analysis, the US prevalence of FH was estimated by applying a modified version of the Dutch Lipid Clinic (DLC) criteria to participants in the 1999 to 2012 National Health and Education National Surveys (NHANES) [7].
According to the DLC definition, individuals are classified as having definite or probable FH based on LDL-C levels, physical examination findings, genetic criteria, and personal and family history of premature ASCVD (coronary artery disease, stroke, or peripheral vascular disease) [8]. It was modified in the sense that some DLC criteria (genetic testing, family history of hypercholesterolemia, personal history of peripheral arterial disease, and relevant physical examination findings) were not collected in NHANES, thus were not considered in this analysis.

Main results

The estimated overall US prevalence of probable/definite FH was 0.40% (95%CI: 0.32–0.48) or 1 in 250 (95%CI: 1 in 311-209).
  • probable FH was estimated to affect 0.38% (95%CI: 0.30–0.45) or 1 in 267 (95%CI: 1 in 334-222)
  • definite FH was estimated as affecting 0.02% (95%CI: 0.01–0.04) or 1 in 4,023 (95%CI: 1 in 15,652-2,309)
FH prevalence varied by:
  • Age: least common in 20 to 29 year olds: 0.06% (1 in 1,557) and most common in 60 to 69 year olds: 0.85% (1 in 118),
  • race/ethnicity: with 0.40% (1 in 249) in whites and 0.47% (1 in 211) in blacks, 0.24% (1 in 414) in Mexican Americans and 0.29% (1 in 343) in other races.
  • Obesity: obese participants: 0.58% (1 in 172), non-obese participants: 0.31% (1 in 325)
  • But not by sex: prevalence was 0.40%, 1 in 250 in both men and women.  


FH, defined with modified Dutch Lipid Clinic criteria available in NHANES, affects 1 in 250 US adults, a higher prevalence than was commonly reported to date. Given that no genetic criteria were considered, the clinical definition used may have led to an underestimation of the true prevalence. White and black populations are more frequently affected than other races, and obesity and age influenced the prevalence estimates, suggesting that clinical criteria may not be sufficient to estimate FH prevalence.

Find this article online at Circulation


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5. Nordestgaard BG, Chapman MJ, Humphries SE, et al; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J.2013;34:3478–390a
6. Shi Z, Yuan B, Zhao D, et al. Familial hypercholesterolemia in China: prevalence and evidence of underdetection and undertreatment in a community population. Int J Cardiol. 2014;174:834–836
7. Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. Accessed October 4, 2014.
8. Benn M, Watts GF, Tybjaerg-Hansen A, et al. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012;97:3956–3964

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