Our study is the first one to assess the association between admission HR and all-mortality and CVE in STEMI patients when accompanied with or without T2DM. The main results are summarized as follows:
In STEMI patients accompanied with T2DM, admis-sion HR, 30-day all-cause mortality and rate of CVE was higher compared with those without T2DM.
Admission HR was an independent risk factor of prognosis in STEMI patients with or without T2DM.
After controlling for baseline and in-hospital therapeutic confounders, the prognostic effect of HR was different between patients with T2DM and without T2DM. In the T2DM patients, the hazard ratios in Q2 and Q3 groups were non- significant, however, it seemed probably due to inefficient power with the relative small sample size. Hazard ratios in each increased HR group were larger in individuals with than without T2DM, and there was a significant interaction effect of HR and diabetic state on 30-day CVE mortality (P = 0.035), which indicated that increased heart rate at any level is more deleterious for prognosis in diabetic than non-diabetic individuals.
Previous studies have shown a positive association between elevated HR and increasing risk of cardiovascular disease (CVD), all-cause and cardiovascular mortality in general people and in patients with various cardiovascular diseases
[1, 3, 14–16], especially AMI. Myocardial ischemia results from an imbalance between coronary blood flow supply and myocardial metabolic demand. HR and other determinants highly affect myocardial oxygen demand
, meanwhile, HR is the major determinant of the supply of blood flow. Some studies
 have shown that elevated HR can stimulate the arterial wall, affect local hemodynamic environment
[19, 20] activate inflammation
, disturb the imbalance between myocardial demand and supply
, and disrupt atherosclerotic plaques
Concomitant T2DM then increases the aforementioned influence further when compared with patients without T2DM, propensity to worse prognosis. First, hyperglycemia may play an important role by several pathophysiological mechanisms
[24–27]. Secondly, these patients have higher HR
Some epidemiologic studies suggest the relationship between HR and outcome in diabetic patients. Stettler et al.
 have reported the prognostic role of HR in patients with T2DM. In the Bremen Diabetes study, higher HR was also related to an increase of cardiovascular death
. However, Anselmino et al.
 reported that in patients with stable CAD, the association between resting HR and CVE can be found in those with diabetes, but not in nondiabetic patients. It’s unknown if the difference retains in acute settings, such as STEMI. Our observation performed after separating T2DM from non-T2DM in STEMI patients, which showed that HR was an independent risk factor of prognosis (P < 0.05) regardless of T2DM.
Cardiac autonomic neuropathy (CAN) is a common chronic complication of T2DM
, and manifests an increase in HR and a reduction in HR variability, that confer higher morbidity and mortality to diabetic patients
[33, 34]. CAN may contribute to the differences identified in the present study. High HR is not considered to diagnose CAN by itself, but it can reflect a relative imbalance in the sympathetic activity and vagal impairment
. It appears that T2DM and autonomic dysfunction are causally related, and a higher HR, elevated high blood pressure, and ischemia burden may be intermediate accelerators
. So that, T2DM may strengthen the predictive effect of HR by CAN, but we also need further study of the internal mechanism to confirm this hypothesis.
Our finding in more than 7 000 patients pointed out that HR at admission was an independent predictor of short-term adverse outcome, including cardiovascular and all-cause mortality despite the high level of treatment with beta-blockers. The results emphasized the different of prognostic effect of HR between the two kinds of population, meanwhile. However, more prospective studies are needed to confirm these findings in larger clinical registries.
First, the study is a subgroup analysis of an existing material, and thereby suffers from limitations and biases of such material. It is not totally equivalent to the real settings. Second, we only observed the all-cause mortality and CVE in 30 days; a longer follow-up may declare more information and elucidate the hypothesis generated in this report. Third, we don’t take blood glucose or glycolated hemoglobin level into account, which reflect the therapeutic effect of T2DM, and may effect the degree of CAN. And the HR in our database is only gained at admission rather than on-treatment or discharge value simultaneously. At last, the sample size of T2DM patients was far less than patients without T2DM (~1/8), and seemed to preclude statistical significance. A larger sample will be needed to improve the statistical power and find out the truth.