Inverse Associations Between Circulating Secreted Frizzled Related Protein 2 (sFRP2) and Cardiometabolic Risk Factors

Abstract

Background: Secreted frizzled-related protein 2 (sFRP2) plays an important role in metabolic syndrome and cardiovascular diseases (CVDs); However, its relevance with cardiometabolic diseases remains to be elucidated. We aimed to determine the serum levels of sFRP2 in patients at different stages of heart failure (HF) with or without type 2 diabetes mellitus (T2DM), and assess the correlation between circulating sFRP2 levels and cardiometabolic risk factors.Methods: In this study, serum samples from 277 patients visiting Zhongshan Hospital affiliated to Fudan University were collected. These patients were clinically diagnosed and categorized as five groups, including the control group, pre-clinical HF group, pre-clinical HF+T2DM group, HF group and HF+T2DM group. Serum sFRP2 levels were measured with enzyme-linked immunosorbent assay (ELISA) tests and the clinical characteristics of each patient were recorded. Spearman rank correlation analysis and multiple stepwise linear regression analysis were conducted. Univariate and multivariate logistic regression analysis were performed to screen risk factors for HF in patients with CVDs.Results: Serum sFRP2 levels were significantly lower in the HF+T2DM group compared with the other four groups. Spearman rank correlation analysis showed that sFRP2 was negatively correlated with parameters including patients' age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), left atrial dimension (LAD) and left ventricular posterior wall (LVPW), and positively correlated with hemoglobin, estimated glomerular filtration rate (eGFR), albumin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and left ventricular ejection fraction (LVEF). However, in multiple regression analysis, significant associations with ln(sFRP2) were observed only in FPG, hs-CRP and LAD. Higher serum sFRP2 was significantly linked to lower odds of HF in patients with CVDs.Conclusion: sFRP2 progressively decreased when glucose homeostasis and cardiac function deteriorated. sFRP2 acted as a risk factor for HF in patients with CVDs, especially in those with concomitant T2DM.

Increased Secreted Frizzled-Related Protein 2 in Hypertension-Induced Left Ventricular Remodeling

“…This is the first clinical study to analyze the changes in sFRP2 levels in patients with HTN. Our previous study found that serum-sFRP2 progressively decreased when cardiac function deteriorated [ 23 ], which made us wonder how sFRP2 levels change during compensated LV remodeling. Since animal research found an initial increase in cardiac sFRP2 under pressure overload [ 12 ], we chose to detect serum sFRP2 in hypertensive patients and found a similar trend.…”

“…The presence of comorbidities, such as diabetes [ 47 ] and metabolic syndrome (MetS) [ 48 ], significantly contribute to LV remodeling. Serum sFRP2 has been reported to be negatively correlated with fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) [ 23 ] and positively correlated with BMI, total fat, and cholesterol [ 49 ]. In this study, the blood glucose and lipid levels were similar between groups B and C, excluding potential confounding factors.…”

Whole‐transcriptome defines novel glucose metabolic subtypes in colorectal cancer

“…These findings indicate that SFRP2 and THBS2 may be vital regulators in abnormal glucose metabolism and CRC progression. Furthermore, as secreted proteins, SFRP2 and THBS2 can be detected by serology 51,52 . Unlike in situ materials, liquid samples are easy to obtain and can be used for early diagnosis and dynamic monitoring, providing a more comprehensive picture of the systemic status 53 .…”

“…Furthermore, as secreted proteins, SFRP2 and THBS2 can be detected by serology. 51 , 52 Unlike in situ materials, liquid samples are easy to obtain and can be used for early diagnosis and dynamic monitoring, providing a more comprehensive picture of the systemic status. 53 Together, our study validated SFRP2 and THBS2 as key regulators that link abnormal glucose metabolism with CRC.…”