Spannella Francesco, Giulietti Federico, Galeazzi Roberta, Passarelli Anna, Re Serena, Di Pentima Chiara, Allevi Massimiliano, Magni Paolo, Sarzani Riccardo
Internal Medicine and Geriatrics, IRCCS INRCA, 60129 Ancona, Italy.
Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy.
Biomedicines. 2022 Aug 12;10(8):1961. doi: 10.3390/biomedicines10081961.
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.
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.
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; = 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, = 0.001) and even after an adjustment for confounding factors (beta = -0.361, = 0.001 for ln(NT-proBNP); beta = -0.330, = 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; = 0.006) and in male patients (r = -0.431, = 0.001).
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.
心脏利钠肽（NPs）具有多种代谢作用，包括对脂质代谢的一些作用。较高的NPs水平可能与良好的血脂谱相关。在体外研究中，已发现NPs通过防止前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）过表达来调节低密度脂蛋白受体（LDLR）的转运。我们研究的目的是在体内研究PCSK9血浆水平与N末端B型利钠肽原（NT-proBNP）之间可能存在的关联。
我们对160例因内科疾病住院的连续老年男性和女性患者进行了横断面研究。排除服用降脂药物的患者和入院诊断为急性心力衰竭的患者。在急性疾病临床稳定后、出院前一天采集空腹血样。
平均年龄为87.8±6.4岁，女性患病率为62.5%。NT-proBNP中位数为2340（814 - 5397）pg/mL。血浆PCSK平均水平为275.2±113.2 ng/mL。我们发现血浆PCSK9与NT-proBNP之间呈负相关（r = -0.280；P = 0.001）。在考虑NT-proBNP三分位数后（第一三分位数血浆PCSK9水平：317.4±123.6 ng/mL，第二三分位数：283.3±101.8 ng/mL，第三三分位数：231.3±99.0 ng/mL，P = 0.001），甚至在对混杂因素进行调整后（ln(NT-proBNP)的β = -0.361，P = 0.001；NT-proBNP三分位数的β = -0.330，P = 0.001），这种关联仍得到证实。在2型糖尿病患者（r = -0.483；P = 0.006）和男性患者（r = -0.431，P = 0.001）中，血浆PCSK9与NT-proBNP之间的相关性强度可能更大。
在我们的实际临床研究中发现PCSK9与NT-proBNP血浆水平之间存在负相关，这支持了NPs可能在胆固醇代谢中起作用的假设，可能是通过对循环中PCSK9浓度的抑制作用，从而增加LDLR的可用性。
