Worldwide Prevalence of Familial Hypercholesterolemia

Quick Takes

  • Incident familial hypercholesterolemia (FH) is estimated at about 1/300 persons worldwide but is 7/100 in persons with premature ischemic heart disease (IHD) and founder effect such as French Canadians, Lebanese Christians, Finns, South Afrikaners, and Ashkenazi Jews, where it may be as high as 1/100.
  • Elevated lipoprotein (a) increases the risk of premature IHD and may result in underestimating the contribution of HeFH in persons with an LDL-C between 160-190 mg/dl.
  • Because of the fourfold increase in cardiovascular events in HeFH related to LDL particles bathing the arterial wall from birth, FH should be considered in all persons with premature IHD and their offspring.

Study Questions:

What is the worldwide estimate of familial hypercholesterolemia (FH) prevalence in subjects with ischemic heart disease (IHD), premature IHD, and severe hypercholesterolemia (≥190 mg/dl) compared with those in the general population?


In this systematic review and meta-analyses, Embase, PubMed, and the Web of Science were searched until June 3, 2019, for peer-reviewed papers and conference abstracts reporting heterozygous FH (HeFH) prevalence in nonfounder populations, revealing 104 studies eligible for inclusion.


Estimates of FH prevalence were pooled using random-effects meta-analyses and were 0.32% (corresponding to 1:313) among 10,921,310 unique subjects in the general population, 3.2% among 84,479 unique subjects with IHD, 6.7% among 31,316 unique subjects with premature IHD, and 7.2% (1:14) among 17,728 unique subjects with severe hypercholesterolemia. FH prevalence in the general population was similar using genetic versus clinical diagnoses. Seventeen of 195 countries (9%) in the world have reported FH prevalence for the general population, leaving 178 (91%) countries in the world with unknown prevalence.


Compared with 1:313 among subjects in the general population, FH prevalence is 10-fold higher among those with IHD, 20-fold higher among those with premature IHD, and 23-fold higher among those with severe hypercholesterolemia. The prevalence of FH is unknown in 90% of countries in the world.


FH is more common than once thought. The literature used in this meta-analysis has shown the prevalence of FH in the general population to have increased from 0.17% of 419,000 persons in 2012 to 0.30% of 10.9 million in 2018. Clearly the increase is related to the number of studies, none of which used the definition of a point mutation in LDLR, PCSK9, or APOB. There are many population genetic studies demonstrating the inadequacy of the Simon Broome and Dutch Lipid Clinic criteria. Genetic studies are considered research by many insurance carriers, and until recently, HeFH with a low-density lipoprotein cholesterol (LDL-C) of 130-160 mg/dl was unheard of, but is not uncommon in the offspring of persons with the HeFH mutation.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Primary Hyperlipidemia

Keywords: Apolipoproteins B, Cholesterol, LDL, Coronary Artery Disease, Dyslipidemias, Heterozygote, Hypercholesterolemia, Hyperlipoproteinemia Type II, Mutation, Myocardial Ischemia, PCSK9 protein, human, Prevalence, Primary Prevention

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