BMI-Dependent Modulation of the Soluble RAGE-Sirtuin-1 Axis by Coffee Type in Coronary Artery Disease

Coffee contains bioactive compounds associated with cardiometabolic benefits, which modulate metabolic pathways of Sirtuin-1. The AGEs-RAGE axis promotes Sirtuin-1 degradation, but soluble RAGE (sRAGE) acts as a decoy receptor, modulating this signaling pathway. In this hypothesis-generating study, we explore whether relatively higher versus lower body mass index (BMI) phenotypes are associated with differential sRAGE responses to caffeinated and decaffeinated coffee in patients with coronary artery disease (CAD).

Thirty patients were allocated into two intervention-sequence groups that differed in mean BMI (n = 15). Group A (higher BMI) received caffeinated coffee followed by decaffeinated coffee; group B (lower BMI) received the inverse sequence. Biomarkers were measured at baseline, 28, and 56 days. Multiple regression models were constructed using sRAGE as the dependent variable and glucose, glycated hemoglobin (HbA1c), homocysteine, lipoprotein(a) (Lp(a)), Sirtuin-1, and small dense LDL (sdLDL) as predictors.

Serum biomarkers remained unchanged; only Sirtuin-1 increased after caffeinated coffee (p = 0.033) in group B. Regression analyses revealed distinct metabolic profiles between groups. Group A: Baseline sRAGE was inversely associated with glucose and Lp(a) (R² = 0.748; p = 0.009). After coffee exposure, these associations disappeared. In group B, homocysteine and sRAGE were associated across all conditions. Furthermore, sRAGE was positively associated with sdLDL and inversely with HbA1c and Sirtuin-1 (R² = 0.862; p = 0.021) after decaffeinated coffee. After caffeinated coffee, sRAGE was positively associated with glucose and SIRT-1, and inversely associated with Lp(a) (R² = 0.908; p = 0.009).

BMI appears to modulate the sRAGE response to coffee intake in CAD patients, with leaner individuals exhibiting a response that is highly dependent on the type of coffee consumed.