Korean Circ J.  2013 Jun;43(6):363-367. 10.4070/kcj.2013.43.6.363.

Familial Hypercholesterolemia and the Atherosclerotic Disease

• Kim YR
• Han KH

• KMID: 2224895
• DOI: http://doi.org/10.4070/kcj.2013.43.6.363

Abstract

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular diseases, and is inherited as an autosomal dominant trait. The prevalence of heterozygous FH is one in five hundred people. Owing to dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations, serum low density lipoprotein-cholesterol (LDL-C) levels are considerably increased from birth. FH is clinically diagnosed by confirmation of family history and characteristic findings such as tendon xanthoma or xanthelasma. Thus, clinical concern and suspicion are important for early diagnosis of the disease. Current guidelines recommend lowering LDL-C concentration to at least 50% from baseline. Statins are shown to lower LDL-C levels with high safety, and thus, have been the drug of choice. However, it is difficult to achieve an ideal level of LDL-C with a single statin therapy in the majority of FH patients. Alternatively, lipid lowering combination therapy with the recently-introduced ezetimibe has shown more encouraging results.

Keyword

Hypercholesterolemia, familial; Low density lipoprotein-cholesterol; Hydroxymethyglutanyl-CoA Reductase Inhibitors; Ezetimibe

MeSH Terms

Azetidines
Cardiovascular Diseases
Early Diagnosis
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hyperlipoproteinemia Type II
Lipoproteins
Parturition
Prevalence
Tendons
Xanthomatosis
Ezetimibe
Azetidines
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipoproteins

Figure

• 

  Fig. 1 Physical signs of heterozygous familial hypercholesterolemia, as a result of cholesterol deposition within macrophages in specific sites. Tendinous xanthomas, for example, manifests first as thickening of, and later as deposits within, extensor tendons. A: lateral borders of thickened Achilles' tendons are shown with arrows. B: tendinous xanthomas can also occur in the extensor tendons of the hands (shown), feet, elbows and knees. C: xanthelasmas are cholesterol deposits in the eyelids. D: arcus cornealis results from cholesterol infiltration around the corneal rim (arrow) (Yuan G, Wang J, Hegele RA. CMAJ 2006;174:1124-9).9)

• 

  Fig. 2 The role of PCSK9 proteins. PCSK9 genes are synthesized in the golgi complex and secreted into the blood. These genes combine with LDL receptors and go through lysosomal degradation. The assumption is that there is a mechanism in which LDL receptors, which underwent endocytosis, are degraded in the Golgi bodies (Akram ON, Bernier A, Petrides F, Wong G, Lambert G. Arterioscler Thromb Vasc Biol 2010;30:1279-81). LDL: low density lipoprotein.15)

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