Targeting Lower A1C Levels May Reduce Mortality in the Elderly

Evidence suggests A1C levels higher than 7% increase the risks of cardiovascular events in elderly patients (70 years or older) with T2D. 

Managing diabetes and preventing associated complications can be difficult, especially for older patients who often need simplified therapies and have several coexisting conditions. Although approaches to treating these patients vary depending on several factors, their target A1C is usually higher than younger patients. Previous studies have suggested that higher (and sometimes lower) A1C levels can be associated with increased mortality risks; however, evidence on how this affects the elderly is limited. Due to the poor generalizability of previously published studies, researchers from Spain wanted to evaluate how different A1C levels would affect cardiovascular outcomes in older patients with T2D. To assess this relationship, they used data from a previously conducted prospective cohort study (ESCARVAL-RISK) that followed up participants with various conditions, including diabetes, for five years.  

The primary outcome of this study was the incidence of major adverse cardiovascular events (MACE), which included death from all causes or admission into the hospital due to coronary heart disease or stroke. The analysis included a total of 5016 participants with diabetes who were at least 70 years old and did not have a previous cardiovascular condition. Participants were considered to have diabetes if they had an FBG >126 mg/dL or were receiving glucose-lowering medications, and this diagnosis was further confirmed using other analytical tests. They used ICD-10 codes to assess the cause of hospitalization among participants and Chi-square tests, the Student T-test, and multivariable Cox models to analyze how variables were related.  

Researchers reported the mean age of participants to be 75.1 years, mean BMI as 29.9 kg/m2, mean diabetes duration of 9.5 years, and mean A1C of 6.8%. A similar number of men and women were included in the study (46.7% versus 53.3%), while a higher percentage of patients had hypertension (76.7%) and dyslipidemia (57.1%). However, most patients did not use insulin (94%) or oral antidiabetic medications (56.7%). Of the 5016 participants included, 807 had cardiovascular events during a mean follow-up of 4.1 years, and the occurrence of study outcomes was 20.6 per 1000 person-years. Additional analysis showed that cardiovascular events among older patients included in this study increased as A1C levels increased, with the lowest percentage of events among those with an A1C <7%. The percentage of patients who experienced a cardiovascular event were 14.2% (n=455), 18.6% (n=210), and 20.7% (n=142) for A1C less than 7%, 7 to 8%, and higher than 8%, respectively.  

Factors such as male gender, heart failure (H.F.), antiplatelet therapy, antithrombotic agents, and not using oral glucose-lowering agents were associated with an increased risk of cardiovascular events; among these patients, effects of PAD, age, creatinine, and A1C were time-dependent. Using the Cox-Aalen model, participants with H.F. had over twice the risk for study outcomes (HR 2.26), male participants had a 61% higher risk (HR 1.61). In contrast, treatment with antiplatelet therapy (HR 1.39) and antithrombotic agents (HR 1.79) showed a similar effect. This analysis additionally showed a protective effect for oral glucose-lowering agents since there was a 26% lower risk of study outcomes with these agents (HR 0.74). In addition, they reported metformin was the most commonly used medication, and sulfonylureas used had lower chances of hypoglycemia. On the other hand, the effect of PAD was found to significantly affect the development of cardiovascular events (HR 3.79), and age (HR 1.04), A1C (HR 1.16), and creatinine (HR 1.44) were also noted to be associated with an increased risk of cardiovascular events when using the standard Cox model. 

Since several factors were associated with an increased risk of cardiovascular events in older patients with T2D, researchers recommend implementing additional strategies to identify and correct such risk factors. They also suggest that treatment options, such as GLP1-RA and SGLT2 inhibitors, that provide positive renal and cardiovascular effects may have benefit. In this study, they also suggest targeting A1C levels <7% among older patients since higher levels were associated with an increased risk of cardiovascular events. Even though higher A1C goals are recommended for the elderly, a study evaluating 65 patients receiving insulin showed that A1C targets were not associated with the risk of hypoglycemia. Therefore, targeting higher A1C levels did not protect against hypoglycemia. Due to the limited number of studies that have evaluated outcomes in older patients with diabetes and the conflicting evidence that has been observed from previous studies, more research is needed to establish the safety of lower A1C goals.  

Practice Pearls: 

• Cardiovascular events increased among elderly patients 70 years or older as A1C levels increased, and were the lowest among those with A1C <7%. 
• Factors that increased the risk of MACE include male gender, H.F., antiplatelet therapy, antithrombotic agents, age, creatinine, A1C, and PAD. 
• Treatment with oral glucose-lowering agents reduced the risk of cardiovascular events by 26%. 
• Targeting an A1C <7% in older patients with diabetes may reduce the risk of cardiovascular events; however, further studies are needed. 

References for “Targeting Lower A1C Levels May Reduce Mortality in the Elderly”:
Orozco-Beltran et al. “The influence of hemoglobin A1c levels on cardiovascular events and all-cause mortality in people with diabetes over 70 years of age. A prospective study,”. Primary Care Diabetes, 2020. 

Medha. “High Blood Sugar Levels Increase CV Risk in Elderly Diabetics: Study.” Medical Dialogues, 2020. 

Munshi et al. “Liberating A1C goals in older adults may not protect against the risk of hypoglycemia”. Journal of Diabetes and its Complications, 2017. 

Palta, et al. “Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988–2011). Diabetes Care, 2017. 

Leyany Feijoo Ramos, PharmD Candidate, LECOM School of Pharmacy