Natriuretic peptides (NPs) modulate vasodilatation and vascular remodelling. In human coronary explants, expression of NPs mRNA and their respective receptors is significantly more pronounced with advanced atherosclerotic lesions.
Aims: We hypothesize that vascular atherosclerosis modulates NP release in vivo during progressive stages of coronary atherosclerosis.
Methods and results: NT-proANP (A) and NT-proBNP (B) were assessed on blood samples of 194 patients. Coronary atherosclerosis was assessed in all patients by angiography and in case of moderate stenosis by fractional flow reserve (FFR), a validated tool for detecting ischemia-inducing stenosis. Significant coronary stenosis was defined as a diameter stenosis (DS) >/=50% and/or positive FFR. Endothelial dysfunction was detected by cold pressure test (CPT) in a subgroup of 99 patients. Patients were divided into: (1) normal group (normal endothelial function, n=19); (2) endothelial dysfunction group (n=17); (3) moderate atherosclerotic group (at least one coronary stenosis <50%, n=86); (4) stenotic group (n=72). A and B were higher in patients with endothelial dysfunction (A: 2951 [1290-3920] fmol/ml; B: 156 [98-170] pg/ml), moderate atherosclerotic (A: 3868 [2250-5890] fmol/ml, p<0.05 vs. normal; B: 162 [84-283] pg/ml) and stenotic group (A: 3934 [2647-5525]; B: 227 [191-784] pg/ml; p<0.05 vs. normal) as compared with normal group (A: 2378 [970-2601] fmol/ml; B: 78 [40-136] pg/ml). During CPT, a mild NT-proANP increase was observed only in patients with endothelial dysfunction (Delta% vs. baseline: 17+/-6, p<0.05). NT-proBNP did not change after CPT in all groups.
Conclusion: Well defined stages of atherosclerosis are characterized by progressive increases in NT-proANP and NT-proBNP levels, beginning with endothelial dysfunction and progressively more pronounced with moderate and severe coronary atherosclerosis irrespective of the underlying myocardial disease.