Plasma levels of proprotein convertase subtilisin/kexintype 9 are inversely associated with N-terminal pro B-type natriuretic peptide in older population

Background and Aims: Cardiac natriuretic peptides (NPs) exert several effects on lipid metabolism. In vitro studies, NPs have been found to modulate low-density lipoprotein receptor (LDLR) trafficking by preventing proprotein convertase subtilisin/kexin type 9 (PCSK9) overexpression. Aim: to investigate an association between plasma PCSK9 levels and N-terminal pro B-type natriuretic peptide (NT-proBNP) in vivo. Methods: We performed a cross-sectional study on 160 consecutive older patients. Patients taking lipid-lowering drugs or with acute heart failure were excluded. Fasting blood samples were collected in stable health condition. Results: Mean age was 87.8±6.4 years with a female prevalence (62.5%). The median NT-proBNP was 2340 (814–5397) pg/mL. The mean plasma PCSK9 was 275.2±113.2 ng/mL. We found an inverse correlation between plasma PCSK9 and NT-proBNP (r = −0.280; p=0.001). This association was confirmed after taking into account NT-proBNP tertiles (plasma PCSK9 levels: 317.4±123.6 ng/mL in the first tertile, 283.3 ± 101.8 ng/mL in the second tertile, 231.3±99.0 ng/mL in the third tertile, p=0.001) and even after an adjustment for confounding factors (beta = −0.361, p=0.001 for ln(NT-proBNP); beta = −0.330, p=0.001 for NT-proBNP tertiles).The strength of the correlation between plasma PCSK9 and NT-proBNP was likely greater in patients affected by type 2 diabetes mellitus (r = −0.483; p=0.006) and in male patients (r = −0.431, p=0.001). Conclusions: The inverse association found between PCSK9 and NT-proBNP plasma levels in our real-life clinical study supports the hypothesis that NPs may play a role in cholesterol metabolism, possibly through an inhibitory action on circulating PCSK9 concentrations, thus increasing the availability of LDLR.