The prevalence of heterozygous familial hypercholesterolemia (HeFH) is most commonly estimated at 1:200-500, though estimates from 1/67 to 1/1000 have been reported. HeFH has been estimated to affect between 14 and 34 million individuals worldwide.
HeFH is associated with a lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) with levels generally 350-550 mg/dL. The major clinical manifestations of FH result from prolonged exposure to high levels of LDL-C leading to the development of atherosclerotic lesions in the heart, brain, and peripheral arteries. This leads to an increased risk of cardiovascular disease (CVD), most commonly coronary artery disease (CAD). Symptoms of ischemia may occur due the restriction of blood flow; however, acute complications such as myocardial infarction (MI) and sudden cardiac death can occur as the first manifestations of CVD. Other manifestations may include xanthomas around the eyelids and within tendons of the elbows, hands, knees, and feet and corneal arcus.
If left untreated, men and women with HeFH typically develop CAD by ages 55 and 60, respectively. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment. HeFH patients with tendon xanthomas have higher risk of CVD compared to FH patients without xanthomas (OR=3.20, 95% CI: 2.12-4.82).
Interventions for HeFH include: surveillance (echocardiogram), clinical monitoring, and medication. Statins have possible adverse events of elevated liver enzymes, myopathy, and potential fetal teratogenicity. Adverse reactions with ezetimibe monotherapy are generally gastrointestinal and usually mild, when taken with a statin adverse events may include: elevated liver enzymes, headache, and myalgia. Trials of PCSK9 inhibitors indicate that there is no significant difference in the frequency of adverse events compared to those on placebo.
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