Trajectories of Long‐Term Normal Fasting Plasma Glucose and Risk of Coronary Heart Disease: A Prospective Cohort Study

BACKGROUND: Fasting plasma glucose (FPG) levels can vary over time and its longitudinal changing patterns may predict cardiometabolic risk. We aim to identify different trajectories of FPG in those who remained normoglycemic and investigate the association between trajectory groups and coronary heart disease risk in a large prospective cohort study. METHODS AND RESULTS: A total of 20 514 subjects between ages 20 and 80 years were included at baseline. All participants had maintained normal FPG throughout an average follow‐up period of 5.8 years. We identified 3 distinct trajectories using a group‐based trajectory model, labeled by initial value and changing pattern: low‐increasing (n=12 694), high‐increasing‐decreasing (n=5330), and high‐decreasing‐increasing (n=2490). The coronary heart disease incidence density among these 3 groups (3.00, 4.05, and 3.26 per 1000 person‐years, respectively) was significantly different (P=0.038). The high‐increasing‐decreasing group was characterized by a starting FPG of 4.80 mmol/L, and increased up to 5.42 mmol/L at age 55, then decreased thereafter. Treating the low‐increasing group as the reference, the age‐ and sex‐adjusted hazard ratio was 1.58 (95% confidence interval, 1.23–2.02) for the high‐increasing‐decreasing group by Cox proportional hazard regression. After adjustment for other potential confounding factors, the hazard ratio is 1.40 (95% confidence interval, 1.08–1.81). The association persisted after adjustment for baseline FPG, mean, or SD of FPG. CONCLUSIONS: Distinct trajectories of long‐term normal FPG are associated with the development of coronary heart disease, which is independent of other metabolic factors including FPG levels. These findings have implications for intervention and prevention of coronary heart disease among individuals who are normoglycemic.