Improvement of atherosclerosis and stiffness of the thoracic descending aorta with cholesterol-lowering therapies in familial hypercholesterolemia

背景：家族性高胆固醇血症（FH）患者的胸主动脉常有动脉粥样硬化形成。经食管的回声心动描记（TEE）可定量评估胸主动脉壁的性质。

目的：研究降胆固醇治疗对家族性高胆固醇血症患者的抗胸动脉粥样硬化作用。

方法：22例家族性高胆固醇血症病人，服用普伐他汀和普罗布考，并限制饮食13个月，22例年龄相当的正常人作为对照组

动粥分数：将降主动脉（DA）分成纵向等长4段，按每段特点和损伤程度用TEE记分，4段总分为动粥分数，用TAS表示。

硬度参数：动脉硬度参数以（SBP/DBP）/（Dmax-Dmin）/Dmin公式计算，用β表示；其中SBP为动脉收缩压，DBP为动脉舒张压，Dmax为射血时最大主动脉容积，Dmin为射血前期最小的主动脉容积。

结果：家族性高胆固醇血症患者的三项指标均有明显降低

项目	疗前	疗后	P
胆固醇	333±45mg/dl	219±39mg/dl	<0.0001
β	9.88±5.03	7.88±3.92	<0.005
TAS	3.61±1.50	2.94±1.22	<0.0005

结论：FH患者的DA从形态学上和生理学上的动脉粥样硬化好发性和严重程度均比同龄正常人要明显高。年纪相对小的FH患者通过严格的降胆固醇治疗，可明显消退动脉粥样硬化。

讨论：本研究之抗动脉粥样硬化作用主要应该是普罗布考的抗氧化或影响基因表达等作用引起，而不是主要由降胆固醇作用引起。

      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 < 0.0001) subjects. Beta in FH (10.35 +/- 4.87) was greater than in normal (5.10 +/- 1.25, P < 0.0001) 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 = 0.52, P <0.02 and r = 0.59, P < 0.005, respectively). In FH patients, beta and TAS correlated   well with pretreatment total cholesterol levels (r = 0.43, P < 0.05 and r = 0.60, P < 0.005, 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 < 0.0001); this was associated with significant decreases in beta and TAS (from 9.88 +/- 5.03 to 7.88 +/- 3.92, P < 0.005, and from 3.61 +/- 1.50 to 2.94 +/- 1.22, P < 0.0005, 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.