Stepwise reduced CV risk with each risk factor variable within target range in T2DM patients

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes

Literature - Rawshani A, Rawshani A, Franzén S et al. - N Engl J Med 2018:379;7

Introduction and methods

T2DM patient have 2-4 times higher risk of death and CV events, compared to general population [1], but a long-lasting decreased risk has been shown in patients with a reduced number of risk factors after behavior modification or pharmacologic therapy [2-3]. However, the extent to which the excess CV risk in T2DM may be mitigated or even eliminated remains unclear.

This study evaluated the association between the number of risk-factor variables within target ranges based on guideline-recommended target levels [4-5] and the excess risk of death and CV outcomes in T2DM patients. Furthermore, the predicting value of various risk factors in the risk of death and CV outcomes was examined.

This cohort study included 271,174 T2DM patients (mean age 60.6 years) who were registered in the Swedish National Diabetes Register between January 1998 and December 2012, matched with 1,355,870 controls registered in the Swedish population register with a mean follow-up of 5.7 years. Age and the following five risk factors were assessed: elevated glycated hemoglobin (HbA1c) level (cutoff value ≥7.0%) , elevated low-density lipoprotein cholesterol (LDL-c) levels (cutoff value ≥2.5 mmol/L), albuminuria (presence of micro or macroalbuminuria), smoking, and elevated blood pressure (BP) (cutoff value ≥140 mmHg for systolic BP or >80 mmHg for diastolic BP).

The primary outcome consisted of all-cause death, fatal or non-fatal acute myocardial infarction (MI), fatal or non-fatal stroke, and hospitalization for heart failure (HF).

Main results

Risk of CV events

  • For each risk-factor variable within the target range, the excess risk of the outcomes decreased stepwise in T2DM patients, with a larger stepwise decrease from younger to older age groups.
  • Patients with all five risk-factor variables inside the target ranges had a non-significant increased risk of death compared to controls (HR: 1.06, 95%CI: 1.00-1.12) and an increased risk of hospitalization for HF (HR: 1.45, 95%CI: 1.34-1.57).
  • Patients with all five risk-factor variables inside the target ranges had a reduced risk of acute MI and stroke, compared to controls (HR: 0.84, 95%CI: 0.75-0.93 and HR: 0.95, 95%CI: 0.84-1.07, respectively).
  • Lowest HR for acute MI was shown in patients aged ≥80 years at baseline and without risk factors outside the target ranges, compared to controls (HR: 0.72, 95%CI: 0.49-1.07).
  • Patients aged ≤55 years with five risk-factor variables outside the target ranges showed highest excess risk of hospitalization for HF, compared to controls (HR: 11.35, 95%CI: 7.16-18.01).

Predictive value risk-factors

  • Smoking, physical activity, marital status, HbA1c level, and use of statins were the five strongest predictors for risk of death in T2DM patients.
  • HbA1c level, systolic BP, LDL-c level, physical activity and smoking were associated with the risk of acute MI.
  • Risk of stroke was primarily predicted by HbA1c level, systolic BP, duration of diabetes, physical activity and atrial fibrillation.
  • The main predictors for hospitalization for HF were atrial fibrillation, a BMI outside the range, low eGFR and high HbA1c level.
  • HbA1c level outside the target range was the strongest or second strongest predictor for risk of the outcomes, and smoking was the strongest predictor of death.


T2DM patients with five risk-factor variables within guideline-recommended target ranges have no excess risk of death, stroke and MI, compared to general Swedish population, demonstrating the importance of behavior modification or pharmacologic therapy in T2DM patients.


1. Rawshani A, Rawshani A, Franzén S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med 2017; 376: 1407-18.

2. Gaede P, Lund-Andersen H, Parving H-H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580-91.

3. Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348: 383-93.

4. Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33: 1635-701.

5. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38: 140-9.

Find this article online at N Engl J Med

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