Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death

Abstract

Background-Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus. Methods and Results-The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19-1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26-1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30-1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18-1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17-2.77; P<0.001) and hospitalization for heart failure (adjusted odds ratio, 4.72; 95% CI, 4.22-5.29; P<0.001). Conclusions-Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population. across the world. As a result, the international prevalence of diabetes mellitus is expected to continue to rise as risk factors for diabetes mellitus become more common. 7,8 Despite the high prevalence and clear association of diabetes mellitus with adverse events, there are few contemporary data on the long-term outcomes from an international cohort of patients with diabetes mellitus. Prior studies have suggested that diabetes mellitus is associated with an increase in risk that is of a magnitude similar to that of the presence of known atherothrombosis.9 Uncertainty about the current longterm outcomes of stable patients with diabetes mellitus has led to significant debate over whether diabetes mellitus is truly a risk equivalent to coronary artery disease in this population.10,11 Furthermore, prior studies have suggested that diabetes mellitus may be associated with an increased risk of heart failure.12 However, it remains unclear whether this association is attributable to causal effects of diabetes mellitus or to other coexisting medical conditions (eg, hypertension, coro...

Prognostic Impact of Diabetes and Prediabetes on Survival Outcomes in Patients With Chronic Heart Failure: A Post‐Hoc Analysis of the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) Trial

“…The prevalence of DM in patients with heart failure (HF) is extremely high (occurring in up to 40–45% of these patients) 7, 8. Not surprisingly, the burden of morbidity and mortality associated with CHF and DM represents, to date, a major challenge for the prospective sustainability of contemporary healthcare systems 8, 9, 10, 11…”

Heart Failure Considerations of Antihyperglycemic Medications for Type 2 Diabetes

“…19 Results from a landmark study by Nichols et al 20 demonstrated an increased HF risk for participants with versus without T2DM across all age groups studied, with an inverse association between age and magnitude of incremental HF risk, ranging from an 11-fold increased HF risk in the youngest age group <45 years, to a 2. 8 21 in which patients with versus without T2DM had a 33% greater incidence of hHF (9.4% versus 5.9%; adjusted hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.18-1.50). Both the incidence of hHF and its incremental risk associated with T2DM observed in the REACH registry are of similar magnitude as for the outcome of cardiovascular death in the same study (8.9% versus 6.0% in participants with versus without T2DM; adjusted HR, 1.38; 95% CI, 1.26-1.52).…”

“…In patients with T2DM in the REACH registry, those with versus without HF at baseline had increased risk for cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17-2.77) and hHF (adjusted odds ratio, 4.72; 95% CI, 4.22-5.29). 21 In subgroups of patients with T2DM enrolled into RCTs, such as the Losartan Intervention for End Point Reduction in Hypertension Study (LIFE) or the Reduction of End Points in Noninsulin-Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan (RENAAL) trials, HF at baseline was associated with up to 12× higher death rates than T2DM individuals without baseline HF. 24,25 Furthermore, the composite of hHF and cardiovascular death occurred 75% more often in patients with versus without T2DM (28.5% of the cohort) in the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity (CHARM) trials program (7599 patients with HF with up to 3.5 years of follow-up), irrespective of whether HF was caused by ischemic heart disease.…”

Canagliflozin

“…6 Although in general their risk of adverse cardiac events is lower than that of patients with T2D and CVD, this population remains at substantial lifetime risk of future ischemic events. 7 Furthermore, cardiovascular events that may not be directly mediated by ischemia, such as heart failure, are also important and occur in patients with and without established CVD. 7 In an analysis of the global REACH registry (Reduction of Atherothrombosis for Continued Health) of ≈20 000 patients with T2D, 1 of 20 patients with T2D and only risk factors for atherosclerosis were hospitalized with heart failure over 4 years of follow-up.…”

“…7 Furthermore, cardiovascular events that may not be directly mediated by ischemia, such as heart failure, are also important and occur in patients with and without established CVD. 7 In an analysis of the global REACH registry (Reduction of Atherothrombosis for Continued Health) of ≈20 000 patients with T2D, 1 of 20 patients with T2D and only risk factors for atherosclerosis were hospitalized with heart failure over 4 years of follow-up. Furthermore, there is substantial heterogeneity of risk in patients with T2D without known CVD.…”