FH is very often characterized as an undertreated and underdiagnosed disease. This is because a large proportion of patients (mostly those with heterozygous FH) are asymptomatic and the disease progresses clinically without symptoms – until the sudden manifestation of severe complications (i.e. cardiovascular events).
The most serious clinical manifestation of FH is CAD. If we look back prior to introduction of statins, the mortality rate of FH patients aged 20-40 was 100 times higher than the rest of the population! In homozygotes, CAD occurs during the first few decades, and patients died (if not treated with hypolipidemics, but especially if not treated with early revascularization and, increasingly, heart transplantation) prior to 30 years of age.
Homozygous FH is a rare condition (although it does not have official “rare disease” status), which is most easily clinically characterized by cholesterol levels > 13 mmol / L, xanthomatosis, and significantly premature manifestation of CVD (even in childhood). The infamously repeated (even in our book) incidence of 1:1,000,000 is likely to increase to reach approximately 1:160,000 to 1:300,000.
In addition to cholesterol levels > 13 mmol / L, elevated LDL-C levels > 8 (usually higher) are also found during blood analysis. Arcus lipoides, xanthelasma palpebrarum, and tendinous xanthomas are vastly more common than in heterozygotes.
In the case of heterozygotes, the course is more severe in men and half of them die from CAD prior to age 60, as opposed to “a mere” 15% of women. Women manifest CAD approximately 9 years later than is observed in men. Men manifest CAD between 42-46 years of age, while in women this occurs between 51-52 years.
According to some authors, aortic stenosis occurs in up to 30% of heterozygous FH.
Central (alterations of cerebral arteries) and peripheral atherosclerosis (particularly PAD) only occur sporadically in patients with FH; however, carotid involvement is encountered fairly often.
Typical xanthoma locations are shown in the picture gallery. They are lipid infiltrates containing histiocytes (tissue macrophages) transformed into foam cells.
Severe heterozygous FH
The definition of severe heterozygous FH is important because this group of patients is at an extremely high risk of CVD and needs the most intense therapy. In the future, these patients will be seen as candidates for “biological therapy” and other modern medical treatments. The conventional criterion for the diagnosis of severe heterozygous FH was an LDL-C level of ≥ 8.0 mmol / L. Today the “severe heterozygous FH” group also includes patients with FH and a combination of other CVD risk factors, even if LDL-C is < 8.0 mmol / L.