Meal-induced changes in cardiometabolic peptides in the context of acute cardiovascular diseases and glucose metabolism

BACKGROUND: Natriuretic peptides (NPs) and copeptin are established cardiovascular biomarkers which can partly affect human metabolism. However, impact of human metabolism on their postprandial regulation in high-risk patients remains insufficiently understood. We aimed to characterize meal-induced changes in MR-proANP, NT-proBNP, and copeptin and to assess how these dynamics relate to acute cardiovascular (CV) events, type 2 diabetes (T2D) and insulin resistance (IR). METHODS: Within the BeLOVE cohort, a subset of 373 participants with acute coronary syndrome, stroke or very high chronic CV risk underwent standardized study-specific mixed-meal testing approximately 3 months after the acute event or 1 month after enrollment for the chronic high-risk group. Fasting and 120-min postprandial concentrations of MR-proANP, NT-proBNP, copeptin, insulin and glucose were assessed. Structural equation models were used to evaluate direct and indirect associations of acute CV events, T2D, and IR (HOMA-IR) with fasting levels and postprandial changes, adjusted for age, sex and BMI. RESULTS: MR-proANP showed the most pronounced meal-induced suppression. NT-proBNP demonstrated only minor and inconsistent postprandial changes. For all peptides, fasting concentrations were the main determinant of their postprandial changes. A recent acute CV event was associated with higher fasting NP levels (MR-proANP: standardized β = 0.22 [0.09; 0.34]; NT-proBNP: β = 0.28 [0.15; 0.41]), but not substantially with their postprandial changes after accounting for their baseline levels. T2D showed no consistent association with fasting or postprandial NP responses. In contrast, higher HOMA-IR was associated with lower fasting MR-proANP (β=-0.19 [-0.30; -0.07]) and a stronger postprandial decline (β=-0.18 [-0.33; -0.04]). Similarly, higher HOMA-IR was linked to lower fasting NT-proBNP (β=-0.15 [-0.28; -0.03]) but showed no clear association to its postprandial change. Copeptin dynamics were largely independent of acute CV disease and metabolic status. CONCLUSIONS: In patients after a recent ACS or stroke, postprandial MR-proANP dynamics are linked to insulin resistance, rather than diabetes status. In contrast, the limited postprandial variability of NT-proBNP and the largely fasting-related changes of copeptin make these markers less suited for capturing short-term metabolic responses. Together, these findings highlight the value of postprandial phenotyping for understanding cardiometabolic regulation and support further evaluation of MR-proANP as a potential biomarker in future prospective studies with cardiovascular outcomes across subjects with and without acute CV event. TRIAL REGISTRATION: The study protocol was approved by the institutional ethics committee (EA1/066/17) and registered in the German Clinical Trials Register (DRKS00016852).