Human coronary atherosclerosis modulates cardiac natriuretic peptide release

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.

We hypothesize that vascular atherosclerosis modulates NP release in vivo during progressive stages of coronary atherosclerosis.

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.

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.