Several large studies have shown that in diabetic patients, HbA1c is a strong predictor of cardiovascular disease, while in non-diabetics, this association is less clear. Results of the first study to examine the association of HbA1c with non-fatal cardiovascular disease in non-diabetics were reported by Esther van't Riet, VU University Medical Center, Amsterdam, the Netherlands. The results showed that, even in non-diabetics, HbA1c elevation significantly increases the risk for non-fatal cardiovascular events.

The Hoorn Study is a population based cohort study of a general population in the Netherlands. The current analysis of cardiovascular events was based on data from 1,674 non-diabetic subjects from the Hoorn Study for whom data on Hb1Ac level, glucose level, and morbidity were available. Over the course of approximately 10 years, 385 non-fatal and 113 fatal cardiovascular events had occurred.

Esther van't Riet reported that whether adjusting only for age and gender or for age and gender plus other traditional cardiovascular risk factors (eg, hypertension, smoking, LDL-cholesterol, triglycerides, and waist-to-hip ratio), subjects with HbA1c >5.6% had a significantly increased risk of a non-fatal cardiovascular event (p<0.05).

This association with fatal cardiovascular events was significant in the model that included only age and gender, but not when adjusted for the other traditional cardiovascular risk factors.

“The clinical meaning of this is that, even in subjects without diabetes, it is very important to maintain optimal glycemic control,” she said. She added, however, that control of blood pressure and cholesterol are still more important than addressing HbA1c.

The study also examined the relationship between fasting plasma glucose and 2-hour-plasma glucose, finding no significant associations with cardiovascular disease, after correction for age, gender and other cardiovascular risk factors. Miss. van't Riet speculated that the reason there was no association with 2-hour-plasma glucose (a relationship that has been reported in prior epidemiological studies) was that diabetic patients were excluded in the current analysis, whereas they were included in the previous studies. In addition, previous research not always adjusted for traditional cardiovascular disease risk factors.