Coronary heart disease and glycemic control
This dissertation investigates the relationship between glycemic control and coronary heart disease in persons with and without diabetes. The increased risk of cardiovascular diseases in persons with diabetes is only partially explained by traditional risk factors such as obesity, dyslipidemia, and hypertension. Chronically elevated glucose levels, the clinically defining feature of diabetes, are most accurately estimated by hemoglobin A1c (HbA1c). It is known that HbA1c levels are directly related to the risk of diabetes-related microvascular (small vessel) disease. However, the relationship between HbA1c and cardiovascular (large vessel) disease risk is unclear.
The first study in this dissertation is a systematic review and meta-analysis of the previous epidemiologic studies which have examined the relationship between HbA1c and cardiovascular disease risk in persons with diabetes. This review suggests a positive association between HbA1c and cardiovascular events, but highlights important weaknesses in the literature.
The second study describes the methods we used to assay HbA1c from stored whole blood samples on a large sample of individuals who participated in the Atherosclerosis Risk in Communities (ARIC) Study. This study demonstrates the reliability of HbA1c measurements from frozen whole blood samples which had been in storage for over a decade.
The third study is a cross-sectional analysis of the relationship between HbA1c, carotid atherosclerosis, and cardiovascular disease risk factors in persons with diabetes in the ARIC Study. This study demonstrates that HbA1c levels are independently associated with carotid atherosclerosis, cholesterol levels, plasma triglycerides, adiposity, and race/ethnicity in adults with diabetes.
The fourth study is a prospective analysis of HbA1c and coronary heart disease events in persons with and without diabetes. This study suggests that elevated HbA1c is an independent risk factor for coronary heart disease. In persons with diabetes, the risk of heart disease was increased at levels below the current clinical cut-point for “good” glycemic control (HbA1c < 7%). In persons without diabetes, HbA 1c was not related to CHD risk below an HbA1c of 4.6% but strongly related to risk above that level. In persons with diabetes, the risk of CHD increased throughout the range of HbA1c. In a fully adjusted linear model, the relative risk of CHD for a 1-percentage point increase in HbA1c was 2.31 (95% CI 1.41 to 3.80) in persons without diabetes and an HbA1c > 4.6%. The relative risk was 1.14 (95% C11.08 to 1.21) in persons with diabetes in a linear model across the full range of HbA1c.
Clinical trials are needed to test the efficacy of specific glucose-lowering interventions, but our results suggest that improvements in glycemic control may reduce coronary heart risk in persons with elevated glucose levels.