A recent study evaluated how diabetes status and A1C influence the risk of myocardial infarction (MI) in men and women.
Diabetes is associated with an increased risk of heart disease, and up to four times higher risk of heart disease mortality. A previous study suggested that higher A1C levels, even years before the onset of a cardiovascular event, increase the risk of death from a myocardial infarction (MI) or stroke. This associated risk may vary depending on gender; however, evidence on these differences is limited. A recent study assessed whether there were differences in the risk of myocardial infarction between men and women by including participants with different diabetes statuses and different A1C levels. Researchers used data from U.K. Biobank between 2006 and 2010 and included 471,399 participants, 56% of whom were women. Those included were between 40 and 69 years old and did not have a history of cardiovascular disease.
After exclusion, investigators divided participants according to diabetes status based on A1C levels and diabetes medications. An A1C lower than 5.7% was described as no diabetes, prediabetes was an A1C between 5.7% and less than 6.5%, undiagnosed diabetes was an A1C of 6.5% or higher without the use of glucose-lowering medications, and previously diagnosed diabetes was categorized based on a self-reported diagnosis or the use of glucose-lowering medications. The primary outcome of this study was the incidence of MI, which researchers obtained using ICD-10 codes from hospital admissions in England, Scotland, and Wales and using national electronic death records. They used Poisson regression models to evaluate the gender-specific incidence and women-minus-men differences in MI occurrence. Cox regression models were also used to analyze hazard ratios depending on gender, the women-to-men ratio of H.R. (RHRs), and the HR and RHRs between a 1% increase in baseline A1C and MI, which was adjusted for diabetes status and analyzed based on depression and sleep features.
At baseline, more men had diabetes (6% versus 3.5%), and both men and women had a median A1C of 6.7% and a median duration of diabetes of 5 years. Both men and women who had prediabetes, undiagnosed diabetes, or previously diagnosed diabetes were found to have a higher risk of MI than those without diabetes. Researchers reported 7316 cases of MI during a mean follow-up period of 8.9 years, of which 30% of patients were women. The incidence of MI was higher in men than women (27.6 per 10,000 person-years for men and 9.3 per 10,000 person-years for women), and this remained across all four diabetes subgroups and A1C levels. On the other hand, when accounting for the presence of diabetes, women with diabetes were found to have a higher risk of MI compared to men (HR 2.33 versus 1.81, respectively), and the women-to-men ratio of H.R. (RHR) was reported to be 1.29, further indicating a higher risk in women. When analyzing A1C levels, both men and women with a previous diabetes diagnosis were at increased risk of MI across different A1C levels. Although some A1C levels were associated more strongly with women, further adjusting for gender-specific confounding effects showed no statistically significant difference.
Researchers found that in both sexes, the risk of MI increased in a log-linear fashion in relation to A1C levels, independently of diabetes status. They noted that each 1% increase in A1C increased the risk of MI by 24% (HR 1.24) in women and by 14% (HR 1.14) in men; however, after accounting for gender-specific confounding, both men and women had 18% (HR 1.18) higher the risk of MI with each 1% increase in A1C. Further analyses showed no difference among genders when adjusting for sex-confounder interactions and no difference in the women-to-men ratio of H.R.s related to age, BMI, or diabetes medications. Changing for depression and sleep characteristics further showed a similar effect among groups.
This study had several limitations, including the self-reporting method used when collecting data and the study population used, limiting generalizability. However, its prospective design and large sample size add value to these results. Findings that even a 1% increase in A1C leads to an increase in MI risk of 18% in both sexes, regardless of diabetes status, emphasizes the importance of more strict control of A1C and diabetes prevention in general. In terms of the higher excess relative risk of MI found in women compared to men in the presence of diabetes, more research in this area is needed to establish a definite association.
- Both men and women with prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were found to have a higher risk of MI than those without diabetes.
- Men had a higher incidence of MI; however, women with diabetes had a higher excess relative risk for MI.
- Each 1% increase in A1C increased the risk of MI by 18% in both men and women, regardless of diabetes status.
Jong, et al. “Diabetes, Glycated Hemoglobin, and the Risk of Myocardial Infarction in Women and Men: A Prospective Cohort Study of the U.K. Biobank.” Diabetes Care, [Publish Ahead of Print, July 27, 2020]
Stevens et al. “Risk Factors for Myocardial Infarction Case Fatality and Stroke Case Fatality in Type 2 Diabetes”. Diabetes Care, 2004
Aronson et al. “Coronary Artery Disease and Diabetes Mellitus.” Cardiology Clinics, 2014.
Leon et al. “Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations, and future research.” World Journal of Diabetes, 2015.
Leyany Feijoo Ramos, PharmD Candidate, LECOM School of Pharmacy