Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Inversely Associated with N-Terminal Pro B-Type Natriuretic Peptide in Older Men and Women

Abstract

Background and Aims: Cardiac natriuretic peptides (NPs) exert several metabolic effects, including some on lipid metabolism. Higher NPs levels are likely to be associated with a favorable lipid profile. In 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. The aim of our study is to investigate a possible association between plasma levels of PCSK9 and N-terminal pro B-type natriuretic peptide (NT-proBNP) in vivo. Methods: We performed a cross-sectional study on 160 consecutive older male and female patients hospitalized for medical conditions. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Fasting blood samples were collected after clinical stabilization of the acute illness, the day before discharge. Results: The 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). Conclusion: 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.

Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities

“…Obese hypertensive patients have reduced plasma NP levels compared to overweight and normal-weight patients. This is primarily due to increased NP clearance mediated by the NPRC overexpression ( 38 , 39 ), driven by hyperinsulinemia secondary to insulin resistance. Also, the glomerular hyperfiltration in obese subjects (glomerular filtration rate and creatinine clearance increase by 0.7 ml/kg in severe obesity) can lead to an increased renal clearance of NT-proBNP.…”