Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus

Abstract

Background: Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population.

Methods: We included all patients ≥18 years of age with T1DM who were registered in the Swedish National Diabetes Register from January 1, 1998, through December 31, 2014, a total of 33 333 patients, each matched for age and sex with 5 controls without diabetes mellitus randomly selected from the population. Patients with T1DM were categorized according to number of risk factors not at target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial infarction, heart failure hospitalization, and stroke was examined in relation to the number of risk factors at target.

Results: The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios for patients achieving all risk factor targets compared with controls were 1.31 (95% confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15-2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke.

Conclusions: A steep-graded association exists between decreasing number of cardiovascular risk factors at target and major adverse cardiovascular outcomes among patients with T1DM. However, risks for all outcomes were numerically higher for patients with T1DM compared with controls, even when all risk factors were at target, with risk for acute myocardial infarction and heart failure hospitalization statistically significantly higher.

Keywords: cardiology; cardiovascular diseases; diabetes mellitus; heart failure; mortality/survival; risk factors.

Figure 1.

Adjusted hazard ratios for all outcomes according to number of risk factors among patients with type 1 diabetes mellitus (T1DM) vs matched controls. A, The incidence rate and excess risk (hazard ratio) for all-cause mortality according to number of risk factors at target in individuals with T1DM compared with control subjects. B, Incidence rates and hazard ratios for acute myocardial infarction. C and D, Incidence rates and hazard ratios for heart failure and stroke, respectively. Crude event rates were calculated as events per 1000 patient-years. Exact Poisson 95% confidence intervals were used. Hazard ratios and incidence rates are pooled from all 5 data sets. Number of events and person-years represent the mean in the 5 data sets.

Figure 2.

Adjusted hazard ratios for all-cause mortality according to number of risk factors among male and female patients with type 1 diabetes mellitus (T1DM) vs matched controls. The figure displays the incidence rate and excess risk (hazard ratio) for all-cause mortality according to number of risk factors at target among male and female patients with T1DM compared with control subjects. Crude event rates were calculated as events per 1000 patient-years. Exact Poisson 95% confidence intervals were used. Hazard ratios and incidence rates are pooled from all 5 data sets. Number of events and person-years represent the mean in the 5 data sets.