Relative risk of CV events similarly increased with resting heart rate irrespective of diabetes status

Introduction and methods

Diabetes is associated with an increased risk of CVD, especially when a patient also has hypertension [1]. Elevated blood pressure (BP) is associated with enhanced resting heart rate (RHR) in patients with diabetes [2], which in itself is a predictor of mortality and CVD in various populations. RHR is associated with various poor health conditions, including incident diabetes [3].

RHR is regulated by the autonomic nervous system and influenced by autonomic imbalance as a result of parasympathetic denervation and sympathetic overactivity in diabetes [4,5]. It is important to know whether high RHR contributes to the higher CVD risk in patients with diabetes, and whether RHR-lowering drugs can potentially modify the RHR-risk association and thus may be a therapeutic option.

The ONTARGET and TRANSCEND studies randomized 31.546patients with high CV risk to ramipril, telmisartan or their combination. 11.730 of those had diabetes and 19806 did not. This analysis aimed to assess the risk at different on-treatment RHR levels in patients with or without diabetes after prior stroke, myocardial infarction (MI), peripheral artery disease (PAD) and at high CV risk on contemporary treatments, using pooled data of ONTARGET and TRANSCEND. RHR and BP were taken after resting for 3 minutes in a sitting position, using an automated validated device, in the presence of the study nurse or investigator. Data of 30.937 patients were used for analysis, 19.450 of whom did not have diabetes, and 11.487 did.

In diabetes patients, on average 8.2 (±2.5) RHR measurements were taken over 54.3 (±11.8) months, and in those without diabetes a mean of 8.4 (±2.5) RHR measurements were done in 55.3 (±10.2) months. The primary composite outcome was composed of CV death, MI, stroke, and hospital admission for heart failure (HHF). Since outcomes were not different between treatment groups in ONTARGET and TRANSCEND, all outcome events were combined for this analysis. Diabetes and non-diabetes patients were categorized into subgroups according to baseline RHR and to their mean achieved in-trail RHR (<60 bpm, 60 to<65, 65 to <70, 70 to <75, 75 to <80 and ≥80 bpm).

Main results

• Patients with diabetes had slightly higher mean in-trial RHR than those without (71.8 ± 9.0 vs. 67.9 ± 8.8, P<0.0001).
• The primary outcome, and its components CV death, HHF and all-cause death were observed more often in patients with RHR ≥80 bpm. The difference in risk associated with higher RHR was less pronounced for MI and absent for stroke.
• As compared with persons without diabetes with RHR 60-65 bpm, patients with diabetes showed a higher risk of the primary outcome, as did diabetes patients with RHR >75 bpm. No statistically significant interaction was found between presence of diabetes and achieved in-trial RHR for all outcomes.
• Different non-linear relationships were observed between RHR and the CV outcomes. For both patients with and without diabetes, an increased risk of the primary outcome, HHF and all-cause death was see above a threshold of on-treatment RHR >75 bpm. For MI, a threshold of ≥80 bpm was seen, and there was no association with stroke.

Conclusion

References

Find this article online at Eur Heart J