Ciulla Michele M, Paliotti Roberta, Esposito Arturo, Dìez Javier, López Begoña, Dahlöf Björn, Nicholls M Gary, Smith Ronald D, Gilles Leen, Magrini Fabio, Zanchetti Alberto
Istituto di Medicina Cardiovascolare and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Ospedale Maggiore IRCCS, Milan, Italy.
Circulation. 2004 Aug 3;110(5):552-7. doi: 10.1161/01.CIR.0000137118.47943.5C. Epub 2004 Jul 26.
In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis.
We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant.
In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
在高血压左心室肥厚（LVH）中，心肌结构因纤维化不成比例增加而改变，但关于抗高血压治疗或个别药物能否诱导心肌纤维化消退，临床证据不足。
我们比较了血管紧张素II受体拮抗剂与β受体阻滞剂对219例经超声心动图证实有LVH的高血压患者心肌胶原容积（通过超声反射率和血清胶原标志物评估）的影响。患者被随机分配接受氯沙坦50至100mg/d（n = 111）或阿替洛尔50至100mg/d（n = 99），加或不加氢氯噻嗪12.5至25mg/d，治疗36周。使用专门设计和验证的软件对心尖中隔的超声图像进行超声反射率分析。获得反射回声的彩色直方图，其分布（宽带[BB]，先前已证明与心内膜活检的胶原容积分数直接相关）用作主要结局指标。胶原合成（PIP、PIIIP）或降解（CITP）的平均色标和血清标志物为次要结局变量。超声反射率分析在106例患者中（氯沙坦组52例，阿替洛尔组54例）证明可行。氯沙坦在36周内降低了BB（从114.5色阶降至104.3色阶，P<0.02），而阿替洛尔治疗使BB增加（从109.0色阶增至113.6色阶，P=无统计学意义），治疗组间差异为-12.8色阶（95%CI -23.6至-2.0，P = 0.02）。接受氯沙坦治疗的患者次要终点（平均色标和胶原标志物）也朝着胶原减少的方向变化，但组间差异无统计学意义。
在有LVH的高血压患者中，氯沙坦可降低心肌胶原含量，而阿替洛尔则不能。两种治疗方法之间的差异具有统计学意义。
