Sex-specific associations of the difference between 2-hour post-load and fasting plasma glucose with cardiovascular risk in a normoglycemic population

Abstract

Abstract Background Elevated levels of fasting plasma glucose (FPG) and 2-hour post-load glucose (2hPG) have been established as individual risk factors for cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. However, it is unclear whether the difference between 2hPG and FPG (2hPG-FPG) within normoglycemic influences the cardiovascular risk in women and men. Purpose To investigate the association between 2hPG-FPG and the incidence of CVD, CHD, and stroke among normoglycemic women and men in a large population-based cohort. Methods In this prospective cohort study, a total of 7224 participants with the normoglycemic state (mean age 37±11; women, 57.4%) that had baseline measurements of both FPG and 2hPG values and did not have prior CVD, CHD, or stroke were included and were followed for incidence of outcomes annually until March 2018. The normoglycemic range was defined as FPG< 5.55 and 2 h-PG< 7.77 mmol/L and not taking anti-diabetic medications. CHD was defined as either positive ECG findings and biomarkers, cardiac symptoms accompanied by either positive ECG or biomarker, or angiographic-proven CHD. Stroke was defined based on the WHO criteria. Also, CVD was defined as a composite of CHD and stroke. A Multivariable Cox­-regression model adjusted for age, body mass index, hypertension, hyperlipidemia, FPG, education level, and smoking status was used to assess the association between 2hPG-FPG and incident CVD, CHD, and stroke in women and men. We also used a cumulative incidence curve to illustrate the cumulative sex-specific incidence of CVD, CHD, and stroke during the follow-up time (Figure 1). Results During a median follow-up of 17.9 years (IQR: 13.75-18.46), 487 CVD (174 women), 427 CHD (140 women), and 76 stroke (37 women) events occurred. Among men, 2hPG-FPG was associated with an increased risk of CVD (hazard ratio [HR]:1.11, 95% confidence interval [CI]:1.01-1.22, p=0.03) and CHD (HR:1.11, 95% CI:1.00-1.22, p=0.04 ), but not stroke (HR:1.14, 95% CI:0.88-1.50, p= 0.33). No significant associations among women were found between 2hPG-FPG and the incidence of outcomes, with adjusted HRs of 1.02 (95% CI, 0.88-1.18, p=0.82), 1.00 (0.85-1.17, p=0.99), and 1.10 (0.80-1.52, p=0.54) for incident CVD, CHD, and stroke, respectively (Table 1). Conclusion A greater difference between 2hPG and FPG (2hPG-FPG) within the normoglycemic range was associated with an increased risk for incidence of CVD and CHD in men but not women. Further studies are warranted to explore the potential use of 2hPG-FPG for cardiovascular risk stratification, particularly among those with normal glucose parameters.Association of 2hPG-FPG with CV riskCumulative incidence of CVD, CHD, stroke