Abstract
Background and aims
Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that is known for its potent anti-inflammatory properties. Nevertheless, little is known regarding the relevance of SFRP5 in coronary artery disease (CAD). The current study examined the correlation between serum levels of SFRP5 and the triglyceride-glucose (TyG) index in patients who underwent coronary angiography (CAG) as a component of cardiovascular assessment and for the purpose of prognosis evaluation.
Methods
A total of 310 hospitalized patients were enrolled in this study between May 2021 and March 2022 and were divided into three groups based on their CAG results and SYNTAX (synergy between PCI with TAXUS drug-eluting stent and cardiac surgery) scores: the control group, mild lesion group, and moderate-severe lesion group. Univariate and multivariate analyses were employed to investigate the relationships between changes in patients and clinical variables. To investigate the impact of the TyG index and serum SFRP5 levels on the occurrence of major adverse cardiovascular events (MACEs), Kaplan‒Meier curves were plotted. Serum SFRP5 levels were measured utilizing an enzyme-linked immunosorbent assay (ELISA) kit.
Results
The serum SFRP5 levels significantly decreased with the increasing severity and complexity of CAD, while the TyG index significantly increased (P < 0.001). Moreover, a significant negative correlation was observed between the serum SFRP5 levels and the TyG index (r = -0.312, P < 0.001). SFRP5 exerts a protective role in different groups of patients. The area under the receiver operating characteristic (ROC) curve indicated that an SFRP5 concentration > 115.58 pg/mL was the best predictive value for CAD (OR:0.87, P < 0.001). MACEs were significantly associated with serum SFRP5 levels and the TyG index, as indicated by both univariate and multivariate Cox regression analyses (P < 0.001). Furthermore, Kaplan‒Meier analysis indicated that as the TyG index decreased and SFRP5 levels increased, the occurrence of MACEs decreased (P < 0.001). Patients with a concentration of SFRP5 > 115.58 pg/mL and a TyG index < 8.49 exhibited a better prognosis for avoiding MACEs (P < 0.001).
Conclusion
These results suggest that the collaboration between serum SFRP5 levels and the TyG index holds promise in predicting CAD and its prognosis.
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Introduction
Coronary atherosclerotic disease and its associated complications are substantial contributors to global mortality and disability [1]. Traditional diagnostic modalities for CAD evaluation include invasive techniques such as selective CAG intravascular ultrasound and optical coherence tomography, all of which are invasive and incur significant costs, thereby constraining their clinical utility [1, 2]. Consequently, there is an urgent need for a practical, low-risk, and cost-effective approach for predicting the occurrence and progression of CAD, as well as for assessing the extent of coronary artery lesions, given the pronounced clinical significance of this pursuit. SFRP5 is a member of the secretory glycoprotein SFRP family that is involved in both insulin resistance and inflammation [3]. Remarkably, SFRP5 exhibits cardioprotective properties, making it a promising candidate as an innovative biomarker for prognosticating the progression of cardiovascular disease [ This study presents novel findings on the correlation between serum SFRP5 levels and the TyG index in patients. It explores the variances in serum SFRP5 levels and the TyG index across different subgroups of CAD while investigating their association with coronary stenosis. The findings propose that the measurement of serum SFRP5 levels and the TyG index holds promise as potential markers to predict the occurrence and progression in patients with CAD, as well as evaluate coronary disease. Nonetheless, it is crucial to acknowledge the limitations inherent in this clinical study. First, the study adopts a cross-sectional study conducted at a single center, which introduces potential bias. Furthermore, the limited sample size undermines the robustness of the results. Additionally, the absence of longer-term follow-up data on adverse cardiovascular events in CAD patients hampers our ability to conduct long-term prognosis assessments. Moreover, it is crucial to explore the underlying mechanisms of SFRP5 in regulating the progression of coronary heart disease. Comprehensive animal experiments are essential to provide insights into these mechanisms. Consequently, it is necessary to conduct large-scale, multicenter, prospective studies, along with additional animal experiments, to validate the diagnostic, severity, and prognostic significance of SFRP5 and the TyG index in relation to CAD. This study has elucidated the critical association between serum SFRP5 levels and the TyG index and their pivotal roles in CAD. Through rigorous analysis, it was demonstrated that while higher levels of serum SFRP5 act as a protective factor, a higher TyG index is associated with an increased risk of CAD. The combined assessment of serum SFRP5 levels and the TyG index has been shown to enhance the predictive accuracy for CAD, surpassing the performance of each biomarker used independently. From a clinical perspective, this integrated approach ensures a more reliable and precise identification of at-risk patients. This facilitates timely and targeted interventions and aids clinicians in stratifying patients based on their risk, leading to a reduction in the incidence of MACEs. Future clinical practices may consider incorporating serum SFRP5 levels and the TyG index as standard elements of CAD risk assessment and management, ensuring that every patient receives the most informed and effective care possible.Study strengths and limitations
Conclusion
Data availability
The datasets analyzed during the current study are not publicly available due to privacy protection but are available from the corresponding author upon reasonable request.
Abbreviations
- SFRP5:
-
Secreted frizzled-related protein 5
- TyG index:
-
Triglyceride-glucose index
- MACE:
-
Major adverse cardiovascular events
- CAD:
-
Coronary artery disease
- CAG:
-
Coronary arteriography
- SYNTAX:
-
Synergy between percutaneous coronary intervention with taxus and cardiac surgery
- IR:
-
insulin resistance
- ANOVA:
-
Analysis of variance
- ELISA:
-
Enzyme-linked immunosorbent assay
- T2DM:
-
Type II diabetes mellitus
- ELISA:
-
Enzyme-linked immunosorbent assay
- ROC:
-
Receiver operating characteristic
- ApoA-1:
-
Apolipoprotein A-1
- ApoB:
-
Apolipoprotein B
- Lp(a):
-
Lipoprotein(a)
- Scr:
-
Serum creatinine
- FBG:
-
Fasting blood glucose
- HbA1c:
-
Glycated hemoglobin
- n-HDL-C:
-
non-HDL-cholesterol
- BMI:
-
Body mass index
- UA:
-
Uric acid
- HDL-C:
-
High-density lipoprotein cholesterol
- LDL-C:
-
Low-density lipoprotein cholesterol
- VLDL-C:
-
very low-density lipoprotein cholesterol
- TG:
-
Triglyceride
- TC:
-
Total cholesterol
- LDH:
-
Lactate dehydrogenase
- FIB:
-
Fibrinogen
- D-D:
-
D-Dimer assay
- CK-MB:
-
Creatine kinase-MB
- eGFR:
-
Estimated glomerular filtration rate
- NLR:
-
Neutrophil-to-lymphocyte ratio
- AUC:
-
Area under the curve
- OR:
-
Odds ratio
- CI:
-
Confidence interval
References
Ralapanawa U, Sivakanesan R. Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: a narrative review. J Epidemiol Glob Health. 2021;11(2):169.
Malakar AKr, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery Disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234(10):16812–23.
Liu L, Shi Z, Ji X, Zhang W, Luan J, Zahr T, et al. Adipokines, adiposity, and Atherosclerosis. Cell Mol Life Sci. 2022;79(5):272.
Zhang J, Jia L, Yang Y, **ao A, Lin X. Lipoprotein (a) and Myocardial Infarction: impact on long-term mortality. Lipids Health Dis. 2023;22(1):70.
Miyoshi T, Doi M, Usui S, Iwamoto M, Kajiya M, Takeda K, et al. Low serum level of secreted frizzled-related protein 5, an anti-inflammatory adipokine, is associated with coronary artery Disease. Atherosclerosis. 2014;233(2):454–9.
Wang D, Zhang Y, Shen C. Research update on the association between SFRP5, an anti-inflammatory adipokine, with obesity, type 2 Diabetes Mellitus and coronary Heart Disease. J Cell Mol Med. 2020;24(5):2730–5.
Navarro-González D, Sánchez-Íñigo L, Pastrana-Delgado J, Fernández-Montero A, Martinez JA. Triglyceride–glucose index (TyG index) in comparison with fasting plasma glucose improved Diabetes prediction in patients with normal fasting glucose: the vascular-metabolic CUN cohort. Prev Med. 2016;86:99–105.
Alizargar J, Bai CH, Hsieh NC, Wu SFV. Use of the triglyceride-glucose index (TyG) in Cardiovascular Disease patients. Cardiovasc Diabetol. 2020;19(1):8. s12933-019-0982–2.
Kappetein AP, Dawkins KD, Mohr FW, Morice MC, Mack MJ, Russell ME, et al. Current percutaneous coronary intervention and coronary artery bypass grafting practices for three-vessel and left main coronary artery Disease.☆Insights from the SYNTAX run-in phase. Eur J Cardiothorac Surg. 2006;29(4):486–91.
Charles-Schoeman C, Buch MH, Dougados M, Bhatt DL, Giles JT, Ytterberg SR, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic Cardiovascular Disease: a post hoc analysis from ORAL surveillance. Ann Rheum Dis. 2023;82(1):119–29.
Chen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q, et al. Effective management of Atherosclerosis progress and hyperlipidemia with nattokinase: a clinical study with 1,062 participants. Front Cardiovasc Med. 2022;9:964977.
Tietge UJF. Hyperlipidemia and Cardiovascular Disease: inflammation, dyslipidemia, and Atherosclerosis. Curr Opin Lipidol. 2014;25(1):94–5.
Zou DP, Chen YM, Zhang LZ, Yuan XH, Zhang YJ, Inggawati A, et al. SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling. Genes Dis. 2021;8(5):677–88.
Van Andel H, Kocemba KA, Spaargaren M, Pals ST. Aberrant wnt signaling in Multiple Myeloma: molecular mechanisms and targeting options. Leukemia. 2019;33(5):1063–75.
Du Y, Zhao Y, Zhu Y, Hu C, Zhang J, Ji Q, et al. High serum secreted frizzled-related protein 5 Levels Associates with early improvement of cardiac function following ST-Segment Elevation Myocardial Infarction treated by primary percutaneous coronary intervention. J Atheroscler Thromb. 2019;26(10):868–78.
Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329(5990):454–7.
Ren Y, Zhao H, Yin C, Lan X, Wu L, Du X, et al. Adipokines, Hepatokines and myokines: Focus on their role and molecular mechanisms in adipose tissue inflammation. Front Endocrinol. 2022;13:873699.
Cheng JX, Yu K. New discovered Adipokines Associated with the pathogenesis of obesity and type 2 Diabetes. Diabetes Metab Syndr Obes Targets Ther. 2022;15:2381–9.
Lu YC, Wang CP, Hsu CC, Chiu CA, Yu TH, Hung WC et al. Circulating secreted frizzled-related protein 5 and wingless-type MMTV integration site family member 5a levels in patients with type 2 Diabetes Mellitus: Sfrp5 and Wnt5a in type 2 Diabetes Mellitus. Diabetes Metab Res Rev. 2013;n/a-n/a.
Hu Z, Deng H, Qu H. Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 Diabetes and negatively correlated with parameters of insulin resistance. Diabetes Res Clin Pract. 2013;99(3):391–5.
Lv C, Jiang Y, Wang H, Chen B. Sfrp5 expression and secretion in adipocytes are up-regulated during differentiation and are negatively correlated with insulin resistance. Cell Biol Int. 2012;36(9):851–5.
Carstensen M, Wiza C, Röhrig K, Fahlbusch P, Roden M, Herder C et al. Effect of Sfrp5 on Cytokine Release and Insulin Action in Primary Human Adipocytes and Skeletal Muscle Cells. Sanchez-Margalet V, editor. PLoS ONE. 2014;9(1):e85906.
Zhao C, Bu X, Wang W, Ma T, Ma H. GEC-derived SFRP5 Inhibits Wnt5a-Induced Macrophage Chemotaxis and Activation. De Re V, editor. PLoS ONE. 2014;9(1):e85058.
Akoumianakis I, Sanna F, Margaritis M, Badi I, Akawi N, Herdman L, et al. Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases. Sci Transl Med. 2019;11(510):eaav5055.
Tong S, Du Y, Ji Q, Dong R, Cao J, Wang Z, et al. Expression of Sfrp5/Wnt5a in human epicardial adipose tissue and their relationship with coronary artery Disease. Life Sci. 2020;245:117338.
Park K, Ahn CW, Lee SB, Kang S, Nam JS, Lee BK, et al. Elevated TyG index predicts progression of coronary artery calcification. Diabetes Care. 2019;42(8):1569–73.
Wu Z, Liu L, Wang W, Cui H, Zhang Y, Xu J, et al. Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients with premature coronary artery Disease: a retrospective cohort study. Cardiovasc Diabetol. 2022;21(1):142.
Guan H, Zhang J, Luan J, Xu H, Huang Z, Yu Q, et al. Secreted Frizzled Related proteins in Cardiovascular and Metabolic Diseases. Front Endocrinol. 2021;12:712217.
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Funding
This research was supported by the Natural Science Foundation of Anhui Province, China (grant number:2008085MH239).
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Conceptualization, Lin Jia; Formal analysis, Lin Jia; Funding acquisition, **anhe Lin; Investigation, Jian Zhang; Methodology, Lin Jia and Shimei Shang; Project administration, Lin Jia; Software, Lin Jia, Shimei Shang and Yu Yang; Supervision, **anhe Lin; Validation, Jian Zhang; Writing – original draft, Lin Jia; Writing – review & editing, Lin Jia and Yu Yang. All authors read and approved the final manuscript.
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The study was approved by the institution’s ethics committee of The First Affiliated Hospital of Anhui Medical University and complied with the Declaration of Helsinki. All patients provided written informed consent to participate in this study, and we concealed information related to patient identity.
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Jia, L., Shang, S., Yang, Y. et al. The synergy of serum SFRP5 levels and the TyG index in predicting coronary artery disease and prognosing major adverse cardiovascular events. Lipids Health Dis 22, 194 (2023). https://doi.org/10.1186/s12944-023-01965-2
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DOI: https://doi.org/10.1186/s12944-023-01965-2