Devereux Richard B, Bang Casper N, Roman Mary J, Palmieri Vittorio, Boman Kurt, Gerdts Eva, Nieminen Markku S, Papademetriou Vasilios, Wachtell Kristian, Hille Darcy A, Dahlöf Björn
From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
Hypertension. 2015 Nov;66(5):945-53. doi: 10.1161/HYPERTENSIONAHA.114.05582. Epub 2015 Sep 21.
In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P≤0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.
在氯沙坦干预降低高血压终点事件（LIFE）研究中，基于氯沙坦与阿替洛尔的4.8年降压治疗减少了左心室肥厚和心血管终点事件，包括心血管死亡和中风。然而，心肌梗死（MI）方面没有差异，这可能与基于阿替洛尔的治疗对心肌氧需求的更大降低有关。在905名LIFE参与者中，通过左心室质量×壁应力×心率（三联乘积）间接评估心肌氧需求。在评估LIFE主要复合终点（心血管死亡、MI或中风）、其各个组成部分以及全因死亡率的预测因素的Cox模型中，三联乘积作为随时间变化的协变量纳入。基线时，与正常成年人相比，两个治疗组中70%的患者三联乘积升高。在随机治疗期间，阿替洛尔使三联乘积降低更多，氯沙坦组三联乘积升高的患病率为51%，而阿替洛尔组为39%（两者P≤0.001）。在对年龄、吸烟、糖尿病以及既往中风、MI和心力衰竭进行校正的Cox回归分析中，三联乘积每降低1个标准差，复合终点事件减少23%（95%置信区间13%-32%），心血管死亡率降低31%（18%-41%），MI降低30%（15%-41%），全因死亡率降低22%（11%-33%）（所有P≤0.001），与中风无关（P=0.34）。尽管基于氯沙坦的治疗使心室质量降低更多，但阿替洛尔使心率降低更多，导致三联乘积降低幅度更大。降压治疗期间较低的三联乘积与LIFE主要复合终点、心血管死亡和MI的较低发生率密切且独立相关，但与中风无关。
