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 90 days after acute event or enrollment. 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. Acute CV events were associated with higher fasting NP levels (MR-proANP: β=0.22 [0.09; 0.34]; NT-proBNP: β=0.28 [0.15; 0.41]), while postprandial dynamics were not after accounting for baseline levels (MR-proANP: β=0.09 [−0.08; 0.25]; NT-proBNP: β=0.09 [−0.08; 0.26]). T2D showed no consistent association with fasting (MR-proANP: β=−0.02 [−0.13; 0.09]; NT-proBNP: β=0.08 [−0.04; 0.20]) or postprandial NP responses (MR-proANP: β=0.00 [−0.14; 0.14]; NT-proBNP: β=−0.05 [−0.18; 0.08]). Higher HOMA-IR was independently 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 not to its postprandial change (β=−0.09 [−0.24; 0.05]). Copeptin dynamics were largely independent of acute CV disease (fasting: β=0.04 [−0.12; 0.20]; postprandial: β=−0.13 [−0.29; 0.02])  and metabolic status (fasting: β=0.07 [−0.06; 0.20], β=0.11 [−0.03; 0.24]; postprandial: β=0.06 [−0.08; 0.19], β=0.01 [−0.13; 0.15] for T2D and HOMA-IR, respectively). CONCLUSIONS: In patients with an acute CV event, postprandial MR-proANP dynamics are linked to insulin resistance. This association suggests that impaired ANP regulation may represent a key component of metabolic inflexibility in high-risk individuals. In contrast, the limited postprandial variability of NT-proBNP and the largely fasting-related changes of copeptin make these markers less suited for capturing shortterm metabolic responses. Together, these findings highlight the value of postprandial phenotyping for understanding cardiometabolic regulation and position MR-proANP as a potential biomarker of metabolic adaptability in future prospective studies with cardiovascular outcomes across subjects with and without acute CV event. TRAIL REGISTRATION: The study protocol was approved by the institutional ethics committee (EA1/066/17) and registered in the German Clinical Trials Register (DRKS00016852).