The major concern for healthcare professionals is the optimal management of diabetes mellitus due to its strong association with cardiovascular events, including coronary heart diseases and strokes and deaths. The established marker for evaluating glucose level at an intermediate term is glycated haemoglobin (HbA1c), as it reflects the average plasma glucose control over a period of 2–3 months.
In the guidelines of HbA1c, 6.5% is a recommended cut-off point for the diagnosis of diabetes. However, the expert group agreed that there is still a lack of sufficient evidence to make any formal recommendation on the interpretation of HbA1c levels below 6.5%. This study explored the relationship between the glycated haemoglobin (HbA1c) level in patients with or without diabetes mellitus and future risks of cardiovascular disease and death.
Based on a national representative cohort, a total of 5277 participants (7% with diabetes) were selected from Taiwan's Triple High Survey in 2002. The comorbidities, medication usages, and outcomes of cardiovascular disease and death, were extracted from the Taiwan’s National Health Insurance Research Database and National Death Registry.
The blood sampling was performed after a 12-hour fasting period. HbA1c was measured using high performance liquid chromatography, quality control was assured under the criteria by the National Glycohemoglobin Standardization Program. An adjusted mercury sphygmomanometer was used to measure blood pressure according the clinical practice guideline for hypertension by the American Society of Hypertension. Participants were asked to rest for at least 30 minutes before measurement of blood pressure. The Cox proportional-hazards regression was used to compare the hazard ratios (HRs) for the outcomes.
After a median follow-up of 9.7 years, participants with diabetes had higher incidence of new onset cardiovascular disease (17.9 versus 3.16 cases per 1000 person-years) and death (20.1 versus 4.96 cases per 1000 person-years) than those without diabetes (all P < 0.001). Diabetes showed increased risk of all-cause death after adjusting for all confounders (adjusted hazard ratio [HR]: 2.29, 95% confidence interval [CI]: 1.52-3.45).
Every 1% increment of HbA1c was positively associated with the risk of total cardiovascular disease (HR: 1.2, 95% CI: 1.08-1.34) and the risk of death (HR: 1.14, 95% CI: 1.03-1.26) for all participants. As compared to the reference group with HbA1c below 5.5%, participants with HbA1c levels ≥7.5% had significantly elevated future risks of total cardiovascular disease (HR: 1.82, 95% CI: 1.01-3.26) and all-cause death (HR: 2.45, 95% CI: 1.45-4.14).
Early endothelial dysfunction and progressive vascular inflammation lead to cardiovascular events. Glycemic management in diabetes has become more complex, including the concerns about the potential confounders such as blood pressure, lipid levels, obesity, and uncertainties regarding the pleotropic effect of intensive glycemic control or cardiovascular medications.
Increased HbA1C level was associated with increased risks of cardiovascular disease and death, the suboptimal glycemic control with HbA1c level over 7.5% (58.5 mmol/mol) was strongly associated with increased risks of stroke, coronary heart disease, and all-cause death, and the risks of ischemic stroke was increased by 1% increment of HbA1c regardless of diabetes diagnosis. We emphasize the importance of optimal glycemic control to prevent cardiovascular diseases and deaths in Taiwan.