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Length and Link of Hemoglobin A1C, Cardiovascular Events, and Type 2 Diabetes

Jun 2, 2020
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Deonna Andrews, PharmD Candidate 2020 of Florida Agricultural & Mechanical University College of Pharmacy and Pharmaceutical Sciences 

Using an A1C value to guide control in patients with type 2 diabetes is well known, but how do these longitudinal values relate to cardiovascular outcomes?  

It is widely known that well-controlled diabetes, often indicated by a lower hemoglobin A1C, is associated with reduced microvascular complications such as nephropathy, retinopathy, and peripheral neuropathy. However, this same concept is not directly correlated with macrovascular complications such as myocardial infarction or ischemic stroke. Also, a previous study showed that lower A1C levels were associated with lower rates of cardiovascular mortality and myocardial infarction, but did not find significant decreases in cardiovascular endpoints with strict glucose control.  

Furthermore, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial had higher rates of cardiac mortality in the target group of A1C levels lower than six percent resulting in its premature halting of the study. Researchers were unable to explain the increased cardiovascular mortality of this trial. It is a suggested possibility that hypoglycemia contributed to this unfortunate incident because it is associated with elevated troponin levels. Additionally, chronic hyperglycemia may lead to vascular damage due to systemic inflammation modulated by reactive oxygen species and advanced glycation end products. Considering this information, it is safe to assume that patients with established coronary artery disease are particularly susceptible to poor glucose control, and there are not many well-conducted studies that have assessed hemoglobin A1C and coronary artery disease. 

The purpose of this study was to assess whether hemoglobin A1C levels were associated with cardiovascular events in patients with diabetes and multivessel coronary artery disease. This was a retrospective study that included 888 patients with type 2 diabetes and multivessel coronary artery disease in the Medicine, Angioplasty, or Surgery Study (MASS). Patients were inclusive of this study if they had multivessel coronary artery disease, stable angina symptoms, or documented myocardial ischemia. Patients were excluded from this study if they had an ejection fraction of 35% or less at baseline, incomplete clinical data regarding cardiovascular outcomes, or lack of hemoglobin A1C measurements during follow-up.  

For statistical analysis, researchers decided to report categorical variables as absolute numbers and percentages and continuous variables as means and standard deviations or as medians and ranges. When comparing categorical data, a Fischer exact test or X2 test was used, and continuous data used the Wilcoxon rank-sum test. Statistical significance was considered with a p-value of less than 0.05. 

Researchers found that of the 888 patients eligible for this study, 140 had no hemoglobin A1C information during follow-up, 7 had incomplete clinical follow-up data, and 16 had an ejection fraction of 0.35 or less. This left the actual study population to decrease to 725 patients. With this final population, 262 patients were included in the endpoints of death, myocardial infarction, or ischemic stroke. There was a one-point increase that was observed in the longitudinal value of the A1C that was significantly associated with a 14% higher risk of the combined endpoint of all-cause mortality, myocardial infarction, and ischemic stroke in the unadjusted analysis with a p-value less than 0.002. When researchers adjusted for the baseline factors, a one-point increase was observed in the longitudinal value of the hemoglobin A1C that was associated with a 22% higher risk of the combined endpoint with a p-value of less than 0.001.  

The limitations of this retrospective study are inclusive of the significant number of patients who were excluded from the trial due to missing data, as well as, the model used in this study to join information between longitudinal outcomes that isnt constant in time with the occurrence of time to event data. However, this study has shown that variations of hemoglobin A1C levels were independently associated with the development of major cardiovascular events in patients with type 2 diabetes and multivessel coronary artery disease during a long-term follow-up period. Researchers believe that hemoglobin A1C control influences both microvascular and macrovascular complications. These findings warrant further investigation into this matter, especially considering the limitations this study has.  

Practice Pearls: 

  • Higher hemoglobin A1C levels are associated with cardiovascular events in patients with diabetes and multivessel coronary artery disease. 
  • An increased hemoglobin A1C was associated with the endpoints of death, myocardial infarction, or ischemic stroke. 
  • Limitations of this study, excluding a significant number of participants, warrant further investigation. 

 

Rezende PC, Hlatky MA, Hueb W, et al. Association of Longitudinal Values of Glycated Hemoglobin With Cardiovascular Events in Patients With Type 2 Diabetes and Multivessel Coronary Artery Disease. JAMA Netw Open. 2020;3(1):e1919666. doi:10.1001/jamanetworkopen.2019.19666 

 

Deonna Andrews, PharmD Candidate 2020 of Florida Agricultural & Mechanical University College of Pharmacy and Pharmaceutical Sciences  

 

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