Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma, Italy.
Heart. 2012 Dec;98(24):1812-6. doi: 10.1136/heartjnl-2012-302795. Epub 2012 Oct 19.
To assess whether reduction of heart rate (HR) has beneficial effects on endothelial function in patients with type 2 diabetes mellitus (T2DM).
Randomised, double-blind, placebo-controlled study.
University hospital.
66 T2DM patients without overt cardiovascular disease.
Patients were randomised to receive for 4 weeks, in addition to their standard therapy, one of the following treatments: atenolol (25 mg twice daily), ivabradine (5 mg twice daily) or placebo (1 tablet twice daily).
Systemic endothelial function, assessed by flow-mediated dilation (FMD); endothelium-independent vasodilation, assessed by nitrate-mediated dilation (NMD); cardiac autonomic function, assessed by HR variability (HRV).
61 patients completed the study (19, 22 and 20 patients in atenolol, ivabradine and placebo groups, respectively). Compared with baseline, HR was similarly reduced by atenolol (87±13 vs 69±9 bpm) and ivabradine (86±12 to 71±9 bpm), but not by placebo (82±10 vs 81±9 bpm) (p<0.001). FMD improved at follow-up in the atenolol group (4.8±1.7 vs 6.4±1.9%), but not in the ivabradine group (5.2±2.5 vs 4.9±2.2%) and in the placebo group (4.8±1.5 vs 4.7±1.7%) (p<0.01). NMD did not change significantly in any group. HRV parameters did not change in the placebo group; they, instead, consistently increased in the atenolol, whereas a mild increase in SDNNi was only observed in the ivabradine group. A significant correlation was found in the atenolol group between HR and FMD changes (r=-0.48; p=0.04).
Despite a comparable reduction in HR, atenolol, but not ivabradine, improved FMD in T2DM patients suggesting that changes in HR are by themselves unlikely to significantly improve endothelial function.
评估降低心率（HR）对 2 型糖尿病（T2DM）患者内皮功能是否有益。
随机、双盲、安慰剂对照研究。
大学医院。
66 例无明显心血管疾病的 T2DM 患者。
患者随机接受以下治疗 4 周：阿替洛尔（每日 2 次，25mg）、伊伐布雷定（每日 2 次，5mg）或安慰剂（每日 2 次，1 片）。
血流介导的扩张（FMD）评估的系统性内皮功能；硝酸盐介导的扩张（NMD）评估的内皮独立扩张；心率变异性（HRV）评估的心脏自主神经功能。
61 例患者完成研究（阿替洛尔组 19 例、伊伐布雷定组 22 例、安慰剂组 20 例）。与基线相比，阿替洛尔（87±13 比 69±9 次/分）和伊伐布雷定（86±12 比 71±9 次/分）同样降低 HR，但安慰剂组（82±10 比 81±9 次/分）没有（p<0.001）。阿替洛尔组 FMD 在随访时改善（4.8±1.7 比 6.4±1.9%），但伊伐布雷定组（5.2±2.5 比 4.9±2.2%）和安慰剂组（4.8±1.5 比 4.7±1.7%）没有（p<0.01）。各组 NMD 均无显著变化。安慰剂组 HRV 参数无变化；相反，阿替洛尔组持续增加，而伊伐布雷定组仅观察到 SDNNi 轻度增加。阿替洛尔组 HR 与 FMD 变化之间存在显著相关性（r=-0.48；p=0.04）。
尽管 HR 降低相似，但只有阿替洛尔而非伊伐布雷定改善 T2DM 患者的 FMD，提示 HR 变化本身不太可能显著改善内皮功能。
