Aims Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes. Methods and results We examined 30 937 patients aged 55 years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56 months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and χ2 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19 450 patients without diabetes and 11 487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P < 0.0001). In the categories of <60 bpm, 60 ≤ 65 bpm, 65 ≤ 70 bpm, 70 ≤ 75 bpm, 75 ≤ 80 bpm and ≥80 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75 ≤ 80 bpm (adjusted hazard ratio [HR] 1.17 (1.01-1.36)) compared to RHR 60 ≤ 65 bpm. For patients with in-trial RHR ≥80 bpm the hazard ratios were highest (diabetes: 1.96 (1.64-2.34), no diabetes: 1.73 (1.49-2.00), For cardiovascular death hazards were also clearly increased at RHR ≥80 bpm (diabetes [1.99, (1.53-2.58)], no diabetes [1.73 (1.38-2.16)]. Similar results were obtained for hospitalization for heart failure and all-cause death while the effect of RHR on myocardial infarction and stroke was less pronounced. Results were robust after adjusting for various risk indicators including beta-blocker use and atrial fibrillation. No significant association to harm was observed at lower RHR. Conclusion Mean RHR above 75-80 b.p.m. was associated with increased risk for cardiovascular outcomes except for stroke. Since in diabetes, high RHR is associated with higher absolute event numbers and patients have higher RHRs, this association might be of particular clinical importance in diabetes. These data suggest that RHR lowering in patients with RHRs above 75-80 b.p.m. needs to be studied in prospective trials to determine if it will reduce outcomes in diabetic and non-diabetic patients at high cardiovascular risk. Clinical Trial registration http://clinicaltrials.gov.Unique identifier: NCT00153101.

中文翻译：

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来自 ONTARGET/TRANSCEND 试验的高心血管风险分析中糖尿病和非糖尿病个体的静息心率和心血管结局

目标 静息心率 (RHR) 已被证明与各种情况下的心血管结局相关。糖尿病患者或非糖尿病患者是否存在不同水平的 RHR 以及与心血管结局的不同关联尚不清楚，因为自主神经病变对血管脆弱性的影响可能在糖尿病患者中更强。方法和结果 我们检查了来自 ONTARGET 和 TRANSCEND 试验的 30937 名 55 岁或以上有心血管疾病病史或有心血管疾病高风险和心肌梗塞、中风或证实有外周血管疾病的患者，这些患者来自 ONTARGET 和 TRANSCEND 试验，研究雷米普利、替米沙坦及其药物。联合治疗的中位时间为 56 个月。我们分析了治疗时平均 RHR 与心血管死亡、心肌梗死、卒中、心力衰竭住院、复合主要结局的组成部分和全因死亡作为连续变量和分类变量。数据分析采用Cox回归分析、ANOVA和χ2检验。这些试验在 ClinicalTrials.gov.number NCT00153101 注册。在 2001 年 12 月 1 日至 2008 年 7 月 31 日（ONTARGET）和 2001 年 11 月 1 日至 2004 年 5 月 30 日（TRANSCEND）期间，从 40 个国家的 733 个中心招募了患者。总共有 19 450 名非糖尿病患者和 11 487 名糖尿病患者按平均 RHR 分层。与非糖尿病患者相比，糖尿病患者的 RHR 更高（71.8 ± 9.0 vs. 67.9 ± 8.8，P < 0.0001）。在 <60 bpm、60 ≤ 65 bpm、65 ≤ 70 bpm、70 ≤ 75 bpm、75 ≤ 80 bpm 和 ≥80 bpm 的类别中，与 RHR 60 ≤ 65 bpm 相比，非糖尿病患者的主要结局风险增加，平均 RHR 为 75 ≤ 80 bpm（调整后的风险比 [HR] 1.17 (1.01-1.36)）。对于试验中 RHR ≥80 bpm 的患者，风险比最高（糖尿病：1.96（1.64-2.34），无糖尿病：1.73（1.49-2.00），对于心血管死亡风险在 RHR ≥80 bpm 时也明显增加（糖尿病[1.99, (1.53-2.58)], 无糖尿病 [1.73 (1.38-2.16)]。心力衰竭住院和全因死亡的结果相似，而 RHR 对心肌梗塞和中风的影响不太明显。结果在调整各种风险指标（包括 β 受体阻滞剂的使用和心房颤动）后保持稳健。在 RHR 较低时未观察到与伤害的显着关联。结论 平均 RHR 高于 75-80 bpm 与除中风外的心血管结局风险增加有关。由于在糖尿病中，高 RHR 与更高的绝对事件数相关，并且患者具有更高的 RHR，这种关联可能在糖尿病中具有特别的临床重要性。这些数据表明，RHR 高于 75-80 bpm 的患者的 RHR 降低需要在前瞻性试验中进行研究，以确定它是否会降低心血管风险高的糖尿病和非糖尿病患者的预后。临床试验注册 http://clinicaltrials.gov. 唯一标识符：NCT00153101。这些数据表明，RHR 高于 75-80 bpm 的患者的 RHR 降低需要在前瞻性试验中进行研究，以确定它是否会降低心血管风险高的糖尿病和非糖尿病患者的预后。临床试验注册 http://clinicaltrials.gov. 唯一标识符：NCT00153101。这些数据表明，RHR 高于 75-80 bpm 的患者的 RHR 降低需要在前瞻性试验中进行研究，以确定它是否会降低心血管风险高的糖尿病和非糖尿病患者的预后。临床试验注册 http://clinicaltrials.gov. 唯一标识符：NCT00153101。