Abhinav Sharma1, Flávio de Souza Brito2, Jie-Lena Sun2, Laine Thomas2, Steven Haffner3, Rury R Holman4, Renato D Lopes5. 1. Duke Clinical Research Institute, Duke University, Durham, NC; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. 2. Duke Clinical Research Institute, Duke University, Durham, NC. 3. Department of Medicine, University of Texas Health Science Center, San Antonio, TX. 4. Diabetes Trials Unit, University of Oxford, Oxford, United Kingdom. 5. Duke Clinical Research Institute, Duke University, Durham, NC. Electronic address: Renato.lopes@duke.edu.
Abstract
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.
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.
Authors: Abhinav Sharma; Adrian Coles; Nishant K Sekaran; Neha J Pagidipati; Michael T Lu; Daniel B Mark; Kerry L Lee; Hussein R Al-Khalidi; Udo Hoffmann; Pamela S Douglas Journal: J Am Coll Cardiol Date: 2019-03-05 Impact factor: 24.094
Authors: Jonathan Afilalo; Abhinav Sharma; Shuaiqi Zhang; J Matthew Brennan; Fred H Edwards; Michael J Mack; James B McClurken; Joseph C Cleveland; Peter K Smith; David M Shahian; Eric D Peterson; Karen P Alexander Journal: J Am Heart Assoc Date: 2018-12-04 Impact factor: 5.501
Authors: Mohammed Yousufuddin; Paul Y Takahashi; Brittny Major; Eimad Ahmmad; Hossam Al-Zubi; Jessica Peters; Taylor Doyle; Kelsey Jensen; Ruaa Y Al Ward; Umesh Sharma; Ashok Seshadri; Zhen Wang; Vinaya Simha; M Hassan Murad Journal: BMJ Open Date: 2019-12-15 Impact factor: 2.692
Authors: Mohammed Yousufuddin; Ye Zhu; Ruaa Al Ward; Jessica Peters; Taylor Doyle; Kelsey L Jensen; Zhen Wang; Mohammad Hassan Murad Journal: Open Heart Date: 2020-03-17