Improvement of atherosclerosis and stiffness of the thoracic descending aorta with cholesterol-lowering therapies in familial hypercholesterolemia.
The thoracic aorta is frequently involved in atherosclerotic lesions associated with familial hypercholesterolemia (FH). Transesophageal echocardiography (TEE) allows quantitative evaluation of the wall properties of the thoracic aorta. Using TEE, we tested whether atherosclerosis of the thoracic aorta in FH could be improved by cholesterol-lowering therapies. The subjects investigated were 22 FH patients and 22 age-matched normal subjects. The descending aorta (DA) was divided into four longitudinal portions of equal length. Atheromatous lesions of each portion of the DA were scored by character and extension of lesions by biplane two-dimensional TEE. The scores of atheromatous lesions from all four portions of the DA were added together to give the total atheromatous score (TAS). We also measured instantaneous dimensional changes of the DA in a cardiac cycle by M-mode TEE and blood pressure by a cuff method and calculated the stiffness parameter beta (In[SBP/DBP]/[Dmax-Dmin]/Dmin), where SBP is the systolic arterial blood pressure, DBP is the diastolic arterial blood pressure, Dmax is the maximum aortic dimension during the ejection period, and Dmin is the minimum aortic dimension during the preejection period. TAS was higher in FH (3.70 +/- 1.32) than normal (0.62 +/- 0.54, P < .0001) subjects. Beta in FH (10.35 +/- 4.87) was greater than in normal (5.10 +/- 1.25, P < .0001) subjects, but there were no significant differences of DA dimensions between the groups. In both normal subjects and FH patients, beta correlated with age (r = .52, P < .02 and r = .59, P < .005, respectively). In FH patients, beta and TAS correlated well with pretreatment total cholesterol levels (r = .43, P < .05 and r = .60, P < .005, respectively). In 12 of 22 FH patients, strict cholesterol-lowering therapies with diet and cholesterol-lowering drugs (pravastatin and probucol) were undertaken for 13 months. Cholesterol levels were significantly decreased from 333 +/- 45 to 219 +/- 39 mg/dL (P < .0001); this was associated with significant decreases in beta and TAS (from 9.88 +/- 5.03 to 7.88 +/- 3.92, P < .005, and from 3.61 +/- 1.50 to 2.94 +/- 1.22, P < .0005, respectively). In FH patients, the incidence and severity of morphological and physiological atherosclerosis of the DA were significantly higher than in age-matched normal subjects. A significant regression of atherosclerosis was achieved by strict cholesterol-lowering therapies in relatively young FH patients.
Tomochika
Y
Y
Second Department of Internal Medicine, Yamaguchi University School of Medicine, Japan.
Okuda
F
F
Tanaka
N
N
Wasaki
Y
Y
Tokisawa
I
I
Aoyagi
S
S
Morikuni
C
C
Ono
S
S
Okada
K
K
Matsuzaki
M
M
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D017548:Echocardiography, Transesophageal; D004548:Elasticity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D015203:Reproducibility of Results
D000924:Anticholesteremic Agents; D017035:Pravastatin; D011341:Probucol