Noncardiovascular deaths are more common than cardiovascular deaths in patients with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: Insights from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial

Am Heart J. 2017 Apr;186:73-82. doi: 10.1016/j.ahj.2016.12.011. Epub 2016 Dec 29.


Background: Patients with impaired glucose tolerance have an elevated risk of cardiovascular (CV) death; however, the causes and risk factors associated with non-CV deaths are poorly understood.

Methods: The NAVIGATOR trial enrolled 9,306 participants with impaired glucose tolerance and CV disease or at high CV risk, with a median follow-up of 6.4years. Using this population, we identified (1) the proportion of deaths attributed to CV, non-CV, and unknown causes, and (2) the risk factors associated with non-CV death.

Results: During the NAVIGATOR trial follow-up, 622 patients died. Investigators reported 244 (39.2%) CV deaths, 313 (50.3%) non-CV deaths, and 65 (10.5%) deaths of unknown cause. Myocardial infarction was the leading cause of investigator-reported death (57/622 [9.2%]). Among non-CV deaths, the most commonly identified cause related to malignancy (177/313 [56.5%]). Using adjudicated causes of death, Cox proportional hazard models identified 3 independent prognostic markers that increased the risk of non-CV death: history of non-melanoma skin cancer (hazard ratio 2.67 [95% CI 1.65-4.33]; P<.0001), white blood cell count (1 unit >5000/mm3; 1.10 [1.02-1.18]; P=.011), and serum potassium levels (per 1mmol/L above any value; 1.67 [1.302.15]; P<.0001).

Conclusions: Despite the high baseline CV risk among patients in the NAVIGATOR trial, the most common cause of death was non-CV. The high burden of non-CV death in this population has potential implications for future CV event-driven trials.

MeSH terms

  • Aged
  • Cardiovascular Diseases / complications*
  • Cardiovascular Diseases / mortality*
  • Cause of Death*
  • Female
  • Follow-Up Studies
  • Glucose Intolerance / complications*
  • Humans
  • Male
  • Middle Aged
  • Risk Factors