Detection and quantitation of calcific atherosclerosis by ultrafast computed tomography in children and young adults with homozygous familial hypercholesterolemia.

Abstract

Ultrafast computed tomography (CT) is a new method for detecting calcific lesions in the coronary arteries. The ability of CT to detect and quantify coronary artery atherosclerosis in children and young adults at risk for malignant atherogenesis was evaluated. A total of 11 consecutive familial hypercholesterolemic (FH) homozygotes (3 to 37 years old) participated. Untreated total cholesterol concentrations were 488 to 1277 mg/dL (12.7 to 33.2 mmol/L). Angiography detected significant lesions in 7 of 11 patients. CT detected calcific atherosclerosis in all 9 of the patients older than 12 years of age, including all those with angina. CT was more sensitive in detecting aortic root and coronary ostial lesions, where atherosclerosis first appears in homozygous FH. The volume of calcification (in cubic millimeters) correlated T he inborn error in cholesterol metabolism that has provided the greatest insight into the role of low-density lipoprotein (LDL) cholesterol in human atherosclerosis is that of familial hypercholesterolemia (FH). More than 150 specific mutations in the LDL receptor gene have been identified that lead to deranged clearance of atherogenic, cholesteryl esterrich LDL particles from the circulation.

Contribution of Genome-Wide Significant Single-Nucleotide Polymorphisms and Antiretroviral Therapy to Dyslipidemia in HIV-Infected Individuals

“…Because the clinical relevance of prolonged dyslipidemia is well documented by studies on genetic causes of dyslipidemia, 46,47 we included all lipid measurements available for each participant and calculated the observed proportions of participants with sustained dyslipidemia during the study period. This was defined, as in our previous reports, 6 48 The observed proportions of participants with sustained dyslipidemia were then assessed according to ART groups and genetic score, summarized into tertiles (supplemental Tables II through IV).…”

Monogenic hypercholesterolemia: new insights in pathogenesis and treatment

“…Atherosclerosis develops initially in the aortic root, causing supravalvular aortic stenosis, and then extends into the coronary ostia. The severity of atherosclerosis is proportional to the extent and duration of elevated plasma LDL-C levels (calculated as the cholesterol-year score) (4). If the LDL-C level is not effectively reduced, FH homozygotes die prematurely of atherosclerotic cardiovascular disease.…”

Pulse Pressure Is an Independent Predictor for the Progression of Aortic Wall Calcification in Patients With Controlled Hyperlipidemia

“…Arterial wall calcification is common in patients with familial hypercholesterolemia, a genetic disorder of cholesterol metabolism. [3][4][5] Several studies have identified the relationship between the serum level of low-density lipoprotein cholesterol (LDL-C) and arterial wall calcification; moreover, lipid-lowering therapy using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been reported to inhibit the progression of arterial wall calcification. 6,7 In patients receiving long-term hemodialysis, elevated serum triglyceride (TG) levels and reduced high-density lipoprotein cholesterol (HDL-C) levels are risk factors for coronary artery calcification.…”

“…Most of the previous studies used the "calcium score" determined by CT as a semiquantitative index of calcification of the aorta or coronary arteries. [3][4][5][6][7] However, the calcium score may not accurately reflect subtle changes in calcium deposit levels. To accurately quantify the degree of calcium deposition, we developed an image color analysis software program that can automatically determine the percentages of calcified volume against whole vascular volume (%ACV) using plain CT. 9 We previously reported a strong correlation between %ACV and aortic calcification dimension in aortas of autopsy specimens, the latter of which was determined using soft X-ray photographs.…”