Familial Hypercholesterolemia and the Atherosclerotic Disease

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.

Grayscale ultrasonic and shear wave elastographic characteristics of the Achilles’ tendon in patients with familial hypercholesterolemia: A pilot study

“…The elastic colour of the Achilles tendon can be delineated clearly with SWE and is in accordance with the findings of grayscale ultrasonography [19]. The elasticity modulus is obtained by using a quantitative analysis system of [1][2][3][4][5][6][7] colour encoding in the software of the ultrasound equipment [20]. SWE generates a stable external force to deform the tissue organization and can be repeated so that the elasticity of the tissue organization can be quantitatively assessed rather than semi-quantitatively assessed.…”

“…The clinical diagnosis of FH is made based on family history, laboratory examinations and representative characteristics, but this disease is very easy to misdiagnose [9]. Some patients are occasionally diagnosed when they develop arterial plaques or myocardial infarction at a young age [3]. Therefore, early diagnosis of FH is an important concern [3].…”

“…Familial hypercholesterolemia (FH) is an autosomal dominant hereditary disease caused by genetic mutations that is characterized by considerably increased levels of serum low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) from birth owing to dysfunction of low-density lipoprotein receptors (LDLR), xanthelasma, thickened Achilles tendons, and premature atherosclerosis [1][2][3].…”

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

“…These findings are considered related to the storage of circulating cholesterol inside macrophages of the extracellular matrix inside the tendons or the skin (Kim and Han, 2013 ; Soslowsky and Fryhofer, 2016 ). The Achilles tendon and the extensor tendons of the dorsum of the hands constitute the most common sites for tendon xanthomas; however, xanthomas may also involve the feet, elbows and antecubital fossae, knees, and buttocks (European Association for Cardiovascular Prevention and Rehabilitation et al, 2011 ; Kim and Han, 2013 ; Soslowsky and Fryhofer, 2016 ). Notably, tendon xanthomas can progress from thickening to tendon deposits, leading to significant changes in tendon biomechanics (Kim and Han, 2013 ; Soslowsky and Fryhofer, 2016 ).…”

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

“…The exact cause of atherosclerosis remains a subject of discussion and has been connected to several distinct mechanisms, hypotheses, and theories [4][5][6][7][8][9][10][11][12][13][14][15][16]. Nonetheless, despite its complexity, atherosclerosis is generally correlated to the levels of cholesterol in plasma [17][18][19][20][21][22]. HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase is involved in the biosynthesis of cholesterol and is subject to feedback regulation by end-products of this same pathway [23][24][25][26].…”