Relationship between the Plasma Fibulin-1 Levels, Pulse Wave Velocity, and Vascular Age in Asymptomatic Hyperuricemia

Abstract

Fibulin-1 (FBLN-1), an elastin-associated extracellular matrix protein, has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease (CVD). We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity (baPWV) in patients with asymptomatic hyperuricemia (AHU). In total, 66 patients with AHU and 66 gender- and age-matched healthy individuals were enrolled. The plasma fibulin-1 levels were measured by immunochemistry. Patients with AHU presented significantly higher vascular age [median (interquartile range): 54 (22) vs. 48 (14) years, P=0.01] and baPWV [mean±SD: 1373±223 vs. 1291±177 cm/s, P=0.02] than the healthy subjects; however, no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects [median (interquartile range): 4018 (3838) vs. 3099 (3405) ng/mL, P=0.31]. A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU (r=0.29, P=0.02); and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age (r=0.22, P=0.08). However, these associations were rendered insignificant after adjustments for potential confounders. In healthy subjects, no correlation was observed between fibulin-1 levels and CVD risk. This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU, but the relationship is not robust.

Keywords

fibulin-1 / cardiovascular risk / vascular age / brachial-ankle pulse wave velocity / asymptomatic hyperuricemia

References

[1] KuwabaraM, NiwaK, HisatomeI, et al.. Asymptomatic Hyperuricemia without Comorbidities Predicts Cardiometabolic Diseases: Five-Year Japanese Cohort Study. Hypertension, 2017, 69(6): 1036-1044

[2] ChoiHK, CurhanG. Independent impact of gout on mortality and risk for coronary heart disease. Circulation, 2007, 116(8): 894-900

[3] ArgravesWS, GreeneLM, CooleyMA, et al.. Fibulins: physiological and disease perspectives. EMBO Rep, 2003, 4(12): 1127-1131

[4] CangemiC, HansenML, ArgravesWS, et al.. Fibulins and their role in cardiovascular biology and disease. Adv Clin Chem, 2014, 67: 245-265

[5] D’AgostinoR S, VasanRS, PencinaMJ, et al.. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation, 2008, 117(6): 743-753

[6] OhkumaT, NinomiyaT, TomiyamaH, et al.. Brachial-Ankle Pulse Wave Velocity and the Risk Prediction of Cardiovascular Disease: An Individual Participant Data Meta-Analysis. Hypertension, 2017, 69(6): 1045-1052

[7] VlachopoulosC, AznaouridisK, Terentes-PrintziosD, et al.. Prediction of cardiovascular events and all-cause mortality with brachial-ankle elasticity index: a systematic review and meta-analysis. Hypertension, 2012, 60(2): 556-562

[8] KuoCF, YuKH, LuoSF, et al.. Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study. Rheumatology (Oxford), 2010, 49(6): 1189-1196

[9] HwangJ, HwangJH, ChungSM, et al.. Association between serum uric acid and arterial stiffness in a low-risk, middle-aged, large Korean population: A cross-sectional study. Medicine, 2018, 97(36): e12086

[10] FeigDI, KangDH, JohnsonRJ. Uric acid and cardiovascular risk. N Engl J Med, 2008, 359(17): 1811-1821

[11] LaugesenE, HoyemP, ChristiansenJS, et al.. Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study. Cardiovasc Diabetol, 2013, 12: 107

[12] CangemiC, SkovV, PoulsenMK, et al.. Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes. Clin Chem, 2011, 57(11): 1556-1565

[13] ScholzeA, BladbjergEM, SidelmannJJ, et al.. Plasma concentrations of extracellular matrix protein fibulin-1 are related to cardiovascular risk markers in chronic kidney disease and diabetes. Cardiovasc Diabetol, 2013, 12: 6

[14] PaapstelK, ZilmerM, EhaJ, et al.. Association Between Fibulin-1 and Aortic Augmentation Index in Male Patients with Peripheral Arterial Disease. Eur J Vasc Endovasc Surg, 2016, 51(1): 76-82

[15] InciA, AkinO, EllidagHY, et al.. Fibulin Levels in Autosomal Dominant Polycystic Kidney Disease and Its Relationship to Arterial Stiffness. Clinical laboratory, 2017, 63(11): 1869-1874

[16] HansenML, RasmussenLM. Associations between plasma fibulin-1, pulse wave velocity and diabetes in patients with coronary heart disease. J Diabetes Complications, 2015, 29(3): 362-366

[17] Yasmin, MaskariRA. The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness. Sci Rep, 2018, 8(1): 8550

[18] DurierS, FassotC, LaurentS, et al.. Physiological genomics of human arteries: quantitative relationship between gene expression and arterial stiffness. Circulation, 2003, 108(15): 1845-1851

[19] RoarkEF, KeeneDR, HaudenschildCC, et al.. The association of human fibulin-1 with elastic fibers: an immunohistological, ultrastructural, and RNA study. J Histochem Cytochem, 1995, 43(4): 401-411

[20] BalbonaK, TranH, GodynaS, et al.. Fibulin binds to itself and to the carboxyl-terminal heparin-binding region of fibronectin. J Biol Chem, 1992, 267(28): 20120-20125

[21] AspbergA, AdamS, KostkaG, et al.. Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican. J Biol Chem, 1999, 274(29): 20444-20449

[22] ArgravesWS, TanakaA, SmithEP, et al.. Fibulin-1 and fibrinogen in human atherosclerotic lesions. Histochem Cell Biol, 2009, 132(5): 559-565

[23] HansenML, DahlJS, ArgravesWS, et al.. Aortic valve stenosis and atrial fibrillation influence plasma fibulin-1 levels in patients treated with coronary bypass surgery. Cardiology, 2013, 126(3): 202-206

[24] ScarinciE, TropeaA, RussoG, et al.. Increased fibulin-1 plasma levels in polycystic ovary syndrome (PCOS) patients: possible contribution to the link between PCOS and cardiovascular risk. J Endocrinol Invest, 2019, 42(1): 91-96