Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Laboratory Analyses
2.3. Statistical Analyses
3. Results
3.1. Serum Bilirubin Concentrations in Patients with Various Forms of Atherosclerosis
3.2. Relationship between Serum Bilirubin Concentration and TAS in Healthy Controls and Patients with Various Forms of Atherosclerosis
3.3. Relationship between Serum Bilirubin, hsCRP, and Other Inflammatory Markers
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Vitek, L. Bilirubin and atherosclerotic diseases. Physiol. Res. 2017, 66, S11–S20. [Google Scholar] [CrossRef]
- Novotny, L.; Vitek, L. Inverse relationship between serum bilirubin and atherosclerosis in men: A meta-analysis of published studies. Exp. Biol. Med. 2003, 228, 568–571. [Google Scholar] [CrossRef]
- Vitek, L.; Novotny, L.; Sperl, M.; Holaj, R.; Spacil, J. The inverse association of elevated serum bilirubin levels with subclinical carotid atherosclerosis. Cerebrovasc. Dis. 2006, 21, 408–414. [Google Scholar] [CrossRef] [PubMed]
- Breimer, L.H.; Wannamethee, G.; Ebrahim, S.; Shaper, A.G. Serum bilirubin and risk of ischemic heart disease in middle-aged British men. Clin. Chem. 1995, 41, 1504–1508. [Google Scholar] [CrossRef]
- Schwertner, H.A.; Fischer, J.R. Comparison of various lipid, lipoprotein, and bilirubin combinations as risk factors for predicting coronary artery disease. Atherosclerosis 2000, 150, 381–387. [Google Scholar] [CrossRef]
- Vitek, L.; Ostrow, J.D. Bilirubin chemistry and metabolism; harmful and protective aspects. Curr. Pharm. Des. 2009, 15, 2869–2883. [Google Scholar] [CrossRef]
- Yang, X.; Li, Y.; Li, Y.; Ren, X.; Zhang, X.; Hu, D.; Gao, Y.; Xing, Y.; Shang, H. Oxidative stress-mediated atherosclerosis: Mechanisms and therapies. Front. Physiol. 2017, 8, 600. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jangi, S.; Otterbein, L.; Robson, S. The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int. J. Biochem. Cell Biol. 2013, 45, 2843–2851. [Google Scholar] [CrossRef]
- Libby, P.; Ridker, P.M.; Maseri, A. Inflammation and atherosclerosis. Circulation 2002, 105, 1135–1143. [Google Scholar] [CrossRef]
- Malekmohammad, K.; Bezsonov, E.E.; Rafieian-Kopaei, M. Role of lipid accumulation and inflammation in atherosclerosis: Focus on molecular and cellular mechanisms. Front. Cardiovasc. Med. 2021, 8, 707529. [Google Scholar] [CrossRef] [PubMed]
- Tangeten, C.; Zouaoui Boudjeltia, K.; Delporte, C.; Van Antwerpen, P.; Korpak, K. Unexpected role of MPO-oxidized LDLs in atherosclerosis: In between inflammation and its resolution. Antioxidants 2022, 11, 874. [Google Scholar] [CrossRef]
- Boudjeltia, K.Z.; Legssyer, I.; Van Antwerpen, P.; Kisoka, R.L.; Babar, S.; Moguilevsky, N.; Delree, P.; Ducobu, J.; Remacle, C.; Vanhaeverbeek, M.; et al. Triggering of inflammatory response by myeloperoxidase-oxidized LDL. Biochem. Cell Biol. 2006, 84, 805–812. [Google Scholar] [CrossRef] [PubMed]
- Jiang, H.; Zhou, Y.; Nabavi, S.M.; Sahebkar, A.; Little, P.J.; Xu, S.; Weng, J.; Ge, J. Mechanisms of oxidized LDL-mediated endothelial dysfunction and its consequences for the development of atherosclerosis. Front. Cardiovasc. Med. 2022, 9, 925923. [Google Scholar] [CrossRef] [PubMed]
- Dichtl, W.; Nilsson, L.; Goncalves, I.; Ares, M.P.; Banfi, C.; Calara, F.; Hamsten, A.; Eriksson, P.; Nilsson, J. Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells. Circ. Res. 1999, 84, 1085–1094. [Google Scholar] [CrossRef] [Green Version]
- Yudkin, J.S.; Stehouwer, C.D.; Emeis, J.J.; Coppack, S.W. C-reactive protein in healthy subjects: Associations with obesity, insulin resistance, and endothelial dysfunction: A potential role for cytokines originating from adipose tissue? Arterioscler. Thromb. Vasc. Biol. 1999, 19, 972–978. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mannes, P.Z.; Tavakoli, S. Imaging immunometabolism in atherosclerosis. J. Nucl. Med. 2021, 62, 896–902. [Google Scholar] [CrossRef] [PubMed]
- Vitek, L. Bilirubin as a signaling molecule. Med. Res. Rev. 2020, 40, 1335–1351. [Google Scholar] [CrossRef] [PubMed]
- Vitek, L.; Tiribelli, C. Bilirubin: The yellow hormone? J. Hepatol. 2021, 75, 1485–1490. [Google Scholar] [CrossRef] [PubMed]
- Jiraskova, A.; Lenicek, M.; Vitek, L. Simultaneous genotyping of microsatellite variations in HMOX1 and UGT1A1 genes using multicolored capillary electrophoresis. Clin. Biochem. 2010, 43, 697–699. [Google Scholar] [CrossRef] [PubMed]
- Vitek, L.; Bellarosa, C.; Tiribelli, C. Induction of mild hyperbilirubinemia: Hype or real therapeutic opportunity? Clin. Pharmacol. Ther. 2019, 106, 568–575. [Google Scholar] [CrossRef] [PubMed]
- Bulmer, A.C.; Blanchfield, J.T.; Toth, I.; Fassett, R.G.; Coombes, J.S. Improved resistance to serum oxidation in Gilbert’s syndrome: A mechanism for cardiovascular protection. Atherosclerosis 2008, 199, 390–396. [Google Scholar] [CrossRef] [PubMed]
- Yesilova, Z.; Serdar, M.; Ercin, C.N.; Gunay, A.; Kilciler, G.; Hasimi, A.; Uygun, A.; Kurt, I.; Erbil, M.K.; Dagalp, K. Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert’s syndrome. J. Gastroenterol. Hepatol. 2008, 23, 1556–1560. [Google Scholar] [CrossRef] [PubMed]
- Vitek, L.; Jirsa, M.; Brodanova, M.; Kalab, M.; Marecek, Z.; Danzig, V.; Novotny, L.; Kotal, P. Gilbert syndrome and ischemic heart disease: A protective effect of elevated bilirubin levels. Atherosclerosis 2002, 160, 449–456. [Google Scholar] [CrossRef]
- Vitek, L.; Novotny, L.; Zak, A.; Stankova, B.; Zima, T.; Polito, A.; Cesare, G.; Zerbinati, C.; Iuliano, L. Relationship between serum bilirubin and uric acid to oxidative stress markers in Italian and Czech populations. J. Appl. Biomed. 2013, 11, 209–221. [Google Scholar] [CrossRef]
- Woronyczova, J.; Novákova, M.; Lenicek, M.; Batovsky, M.; Bolek, E.; Cifkova, R.; Vitek, L. Serum bilirubin concentrations and the prevalence of Gilbert syndrome in elite athletes. Sports Med. Open Access 2022, 8, 84. [Google Scholar] [CrossRef]
- Gopinathan, V.; Miller, N.J.; Milner, A.D.; Rice-Evans, C.A. Bilirubin and ascorbate antioxidant activity in neonatal plasma. FEBS Lett. 1994, 349, 197–200. [Google Scholar] [CrossRef] [Green Version]
- Hammermann, C.; Goldstein, R.; Kaplan, M.; Eran, M.; Goldschmidt, D.; Eidelman, A.I. Bilirubin in the premature: Toxic waste or natural defense? Clin. Chem. 1998, 44, 2551–2553. [Google Scholar] [CrossRef] [Green Version]
- Shekeeb, S.M.; Kumar, P.; Sharma, N.; Narang, A.; Prasad, R. Evaluation of oxidant and antioxidant status in term neonates: A plausible protective role of bilirubin. Mol. Cell Biochem. 2008, 317, 51–59. [Google Scholar] [CrossRef]
- Yeum, K.J.; Russell, R.M.; Krinsky, N.I.; Aldini, G. Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compartments of human plasma. Arch. Biochem. Biophys. 2004, 430, 97–103. [Google Scholar] [CrossRef] [PubMed]
- Sedlak, T.W.; Snyder, S.H. Bilirubin benefits: Cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics 2004, 113, 1776–1782. [Google Scholar] [CrossRef] [PubMed]
- Tapan, S.; Karadurmus, N.; Dogru, T.; Ercin, C.N.; Tasci, I.; Bilgi, C.; Kurt, I.; Erbil, M.K. Decreased small dense LDL levels in Gilbert’s syndrome. Clin. Biochem. 2011, 44, 300–303. [Google Scholar] [CrossRef]
- Boon, A.C.; Hawkins, C.L.; Bisht, K.; Coombes, J.S.; Bakrania, B.; Wagner, K.H.; Bulmer, A.C. Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome. Free Radic. Biol. Med. 2012, 52, 2120–2127. [Google Scholar] [CrossRef]
- Maruhashi, T.; Soga, J.; Fujimura, N.; Idei, N.; Mikami, S.; Iwamoto, Y.; Kajikawa, M.; Matsumoto, T.; Kihara, Y.; Chayama, K.; et al. Hyperbilirubinemia, Augmentation of Endothelial Function and Decrease in Oxidative Stress in Gilbert Syndrome. Circulation 2012, 126, 598–603. [Google Scholar] [CrossRef] [Green Version]
- Boren, J.; Chapman, M.J.; Krauss, R.M.; Packard, C.J.; Bentzon, J.F.; Binder, C.J.; Daemen, M.J.; Demer, L.L.; Hegele, R.A.; Nicholls, S.J.; et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: Pathophysiological, genetic, and therapeutic insights: A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2020, 41, 2313–2330. [Google Scholar] [CrossRef] [Green Version]
- Brown, A.J.; Jessup, W. Oxysterols and atherosclerosis. Atherosclerosis 1999, 142, 1–28. [Google Scholar] [CrossRef]
- Feng, J.F.; Lu, L.; Dai, C.M.; Wang, D.; Yang, Y.H.; Yang, Y.W.; Liu, Y.S. Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages. Clin. Biochem. 2016, 49, 692–698. [Google Scholar] [CrossRef]
- Wu, R.; Feng, J.; Yang, Y.; Dai, C.; Lu, A.; Li, J.; Liao, Y.; Xiang, M.; Huang, Q.; Wang, D.; et al. Significance of serum total oxidant/antioxidant status in patients with colorectal cancer. PLoS ONE 2017, 12, e0170003. [Google Scholar] [CrossRef]
- Veglia, F.; Cavalca, V.; Tremoli, E. OXY-SCORE: A global index to improve evaluation of oxidative stress by combining pro- and antioxidant markers. Methods Mol. Biol. 2010, 594, 197–213. [Google Scholar] [CrossRef]
- Danesh, J.; Wheeler, J.G.; Hirschfield, G.M.; Eda, S.; Eiriksdottir, G.; Rumley, A.; Lowe, G.D.; Pepys, M.B.; Gudnason, V. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N. Engl. J. Med. 2004, 350, 1387–1397. [Google Scholar] [CrossRef]
- Ridker, P.M. High-sensitivity C-reactive protein: Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001, 103, 1813–1818. [Google Scholar] [CrossRef]
- Yeniova, A.O.; Kucukazman, M.; Ata, N.; Dal, K.; Kefeli, A.; Basyigit, S.; Aktas, B.; Agladioglu, K.; Akin, K.O.; Ertugrul, D.T.; et al. High-sensitivity C-reactive protein is a strong predictor of non-alcoholic fatty liver disease. Hepatogastroenterology 2014, 61, 422–425. [Google Scholar]
- Lee, J.; Yoon, K.; Ryu, S.; Chang, Y.; Kim, H.R. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men. PLoS ONE 2017, 12, e0172666. [Google Scholar] [CrossRef] [Green Version]
- Cardoso-Saldana, G.C.; Medina-Urrutia, A.X.; Posadas-Romero, C.; Juarez-Rojas, J.G.; Jorge-Galarza, E.; Vargas-Alarcon, G.; Posadas-Sanchez, R. Fatty liver and abdominal fat relationships with high C-reactive protein in adults without coronary heart disease. Ann. Hepatol. 2015, 14, 658–665. [Google Scholar] [CrossRef]
- Ghule, A.; Kamble, T.K.; Talwar, D.; Kumar, S.; Acharya, S.; Wanjari, A.; Gaidhane, S.A.; Agrawal, S. Association of serum high sensitivity C-reactive protein with pre-diabetes in rural population: A two-year cross-sectional study. Cureus 2021, 13, e19088. [Google Scholar] [CrossRef]
- Mahajan, A.; Tabassum, R.; Chavali, S.; Dwivedi, O.P.; Bharadwaj, M.; Tandon, N.; Bharadwaj, D. High-sensitivity C-reactive protein levels and type 2 diabetes in urban North Indians. J. Clin. Endocrinol. Metab. 2009, 94, 2123–2127. [Google Scholar] [CrossRef]
- Chen, B.; Cui, Y.; Lei, M.; Xu, W.; Yan, Q.; Zhang, X.; Qin, M.; Xu, S. C-reactive protein levels in relation to incidence of hypertension in Chinese adults: Longitudinal analyses from the China Health and Nutrition Survey. Int. J. Hypertens. 2021, 2021, 3326349. [Google Scholar] [CrossRef]
- Qian, X.; He, S.; Wang, J.; Gong, Q.; An, Y.; Li, H.; Chen, Y.; Li, G. Prediction of 10-year mortality using hs-CRP in Chinese people with hyperglycemia: Findings from the Da Qing diabetes prevention outcomes study. Diabetes Res. Clin. Pract. 2021, 173, 108668. [Google Scholar] [CrossRef]
- Petrtyl, J.; Dvorak, K.; Stritesky, J.; Lenicek, M.; Jiraskova, A.; Smid, V.; Haluzik, M.; Bruha, R.; Vitek, L. Association of serum bilirubin and functional variants of heme oxygenase 1 and bilirubin UDP-glucuronosyl transferase genes in Czech adult patients with non-alcoholic fatty liver disease. Antioxidants 2021, 10, 2000. [Google Scholar] [CrossRef]
- Vitek, L. The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases. Front. Pharmacol. 2012, 3, 55. [Google Scholar] [CrossRef] [Green Version]
- Hwang, H.J.; Lee, S.W.; Kim, S.H. Relationship between bilirubin and C-reactive protein. Clin. Chem. Lab. Med. 2011, 49, 1823–1828. [Google Scholar] [CrossRef]
- Yu, K.; Kim, C.; Sung, E.; Shin, H.; Lee, H. Association of serum total bilirubin with serum high sensitivity C-reactive protein in middle-aged men. Korean J. Fam. Med. 2011, 32, 327–333. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.Y.; Bian, L.Q.; Kim, S.J.; Zhou, C.C.; Choi, Y.H. Inverse relation of total serum bilirubin to coronary artery calcification score detected by multidetector computed tomography in males. Clin. Cardiol. 2012, 35, 301–306. [Google Scholar] [CrossRef]
- Lippi, G.; Targher, G. Further insights on the relationship between bilirubin and C-reactive protein. Clin. Chem. Lab. Med. 2012, 50, 2229–2230. [Google Scholar] [CrossRef] [PubMed]
- Deetman, P.E.; Bakker, S.J.; Dullaart, R.P. High sensitive C-reactive protein and serum amyloid A are inversely related to serum bilirubin: Effect-modification by metabolic syndrome. Cardiovasc. Diabetol. 2013, 12, 166. [Google Scholar] [CrossRef] [Green Version]
- Ghosh, P.; Dasgupta, J.; Mandal, T.; Bhattacharjee, D. Correlation of serum bilirubin with inflammatory marker hsCRP in metabolic syndrome disorder. IOSR J. Biotechnol. Biochem. 2016, 2, 27–31. [Google Scholar]
- Dullaart, R.P.; Gruppen, E.G.; Connelly, M.A.; Lefrandt, J.D. A pro-inflammatory glycoprotein biomarker is associated with lower bilirubin in metabolic syndrome. Clin. Biochem. 2015, 48, 1045–1047. [Google Scholar] [CrossRef] [PubMed]
- Roy, S.; Banerjee, U.; Dasgupta, A. Protective role of bilirubin against increase in hsCRP in different stages of hypothyroidism. Indian J. Clin. Biochem. 2016, 31, 43–49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoshino, S.; Hamasaki, S.; Ishida, S.; Kataoka, T.; Yoshikawa, A.; Oketani, N.; Saihara, K.; Okui, H.; Shinsato, T.; Ichiki, H.; et al. Relationship between bilirubin concentration, coronary endothelial function, and inflammatory stress in overweight patients. J. Atheroscler. Thromb. 2011, 18, 403–412. [Google Scholar] [CrossRef] [Green Version]
- Duman, H.; Ozyurt, S. Low serum bilirubin levels associated with subclinical atherosclerosis in patients with obstructive sleep apnea. Interv. Med. Appl. Sci. 2018, 10, 179–185. [Google Scholar] [CrossRef]
- Tekeşin, A.; Tunç, A. Evaluation of inflammatory markers in patients with migraine. Arch. Clin. Exp. Med. 2019, 4, 37–40. [Google Scholar] [CrossRef] [Green Version]
- Mazzone, G.L.; Rigato, I.; Ostrow, J.D.; Bossi, F.; Bortoluzzi, A.; Sukowati, C.H.C.; Tedesco, F.; Tiribelli, C. Bilirubin inhibits the TNF alpha-related induction of three endothelial adhesion molecules. Biochem. Biophys. Res. Comm. 2009, 386, 338–344. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Huang, B.; Ye, T.; Wang, Y.; Xia, D.; Qian, J. Physiological concentrations of bilirubin control inflammatory response by inhibiting NF-kappaB and inflammasome activation. Int. Immunopharmacol. 2020, 84, 106520. [Google Scholar] [CrossRef]
- Zelenka, J.; Dvorak, A.; Alan, L.; Zadinova, M.; Haluzik, M.; Vitek, L. Hyperbilirubinemia protects against aging-associated inflammation and metabolic deterioration. Oxidative Med. Cell. Longev. 2016, 2016, 6190609. [Google Scholar] [CrossRef] [Green Version]
- Tedgui, A.; Mallat, Z. Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiol. Rev. 2006, 86, 515–581. [Google Scholar] [CrossRef] [Green Version]
- Black, S.; Kushner, I.; Samols, D. C-reactive protein. J. Biol. Chem. 2004, 279, 48487–48490. [Google Scholar] [CrossRef] [Green Version]
- Mallat, Z.; Besnard, S.; Duriez, M.; Deleuze, V.; Emmanuel, F.; Bureau, M.F.; Soubrier, F.; Esposito, B.; Duez, H.; Fievet, C.; et al. Protective role of interleukin-10 in atherosclerosis. Circ. Res. 1999, 85, e17–e24. [Google Scholar] [CrossRef]
- Sproston, N.R.; Ashworth, J.J. Role of C-reactive protein at sites of inflammation and infection. Front. Immunol. 2018, 9, 754. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Badimon, L.; Pena, E.; Arderiu, G.; Padro, T.; Slevin, M.; Vilahur, G.; Chiva-Blanch, G. C-reactive protein in atherothrombosis and angiogenesis. Front. Immunol. 2018, 9, 430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McEver, R.P. Selectins: Lectins that initiate cell adhesion under flow. Curr. Opin. Cell. Biol. 2002, 14, 581–586. [Google Scholar] [CrossRef]
- Dong, Z.M.; Chapman, S.M.; Brown, A.A.; Frenette, P.S.; Hynes, R.O.; Wagner, D.D. The combined role of P- and E-selectins in atherosclerosis. J. Clin. Investig. 1998, 102, 145–152. [Google Scholar] [CrossRef] [Green Version]
- Galkina, E.; Ley, K. Vascular adhesion molecules in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 2292–2301. [Google Scholar] [CrossRef] [PubMed]
- Vitek, L. Bilirubin as a predictor of diseases of civilization. Is it time to establish decision limits for serum bilirubin concentrations? Arch. Biochem. Biophys. 2019, 672, 108062. [Google Scholar] [CrossRef]
- Creeden, J.F.; Gordon, D.M.; Stec, D.E.; Hinds, T.D., Jr. Bilirubin as a metabolic hormone: The physiological relevance of low levels. Am. J. Physiol. Endocrinol. Metab. 2021, 320, E191–E207. [Google Scholar] [CrossRef] [PubMed]
Group | Premature Atherosclerosis | IHD | PAD | Controls |
---|---|---|---|---|
(n = 129) | (n = 43) | (n = 69) | (n = 225) | |
All | 10.3 * | 9.8 * | 8.5 * | 12.2 |
[7.6–14.7] | [7.8–11.5] | [6.3–11.3] | [9.0–17.5] | |
Males | 11.3 * | 9.1 * | 9.1 * | 12.8 |
[7.7–16.2] | [7.7–11.0] | [6.8–11.7] | [10.1–18.2] | |
Females | 9.0 | 10.6 | 7.7 * | 10.6 |
[6.7–12.9] | [8.0–17.5] | [6.3–11] | [8.4–16.2] |
All | Premature Atherosclerosis | IHD | PAD | Controls |
---|---|---|---|---|
(n = 75) | (n = 35) | (n = 67) | (n = 190) | |
6/6 | 8.2 * | 8.2 * | 7.6 * | 10.1 |
[6.8–11.2] | [6.8–10.5] | [6.3–11] | [7.9–12.3] | |
6/7 | 12 | 10 | 8.2 * | 12.7 |
[7.9–16.2] | [7.6–12] | [5.6–10.1] | [9.2–16.2] | |
7/7 | 18.8 | 25.3 | 12.2 * | 22.3 |
[10.5–25.7] | [14.9–36.1] | [8.8–23] | [17.7–35.2] | |
Males | (n = 58) | (n = 23) | (n = 34) | (n = 103) |
6/6 | 8.3 * | 8.5 * | 8.7 | 10.6 |
[6.8–11.9] | [6.2–10.7] | [6.3–12.5] | [9.0–12.7] | |
6/7 | 12.6 | 9.9 * | 9.1 * | 14.2 |
[10.3–16.8] | [8.0–11.7] | [7.3–10.5] | [10.6–18.6] | |
7/7 | 18.8 * | ND | 17.9 | 29.7 |
[9.3–25.1] | [6.2–31.2] | [17.7–42.6] | ||
Females | (n = 17) | (n = 12) | (n = 33) | (n = 87) |
6/6 | 7.9 | 8.1 | 7.1 | 9.1 |
[6.4–10.4] | [6.2–9.9] | [6.2–9.8] | [6.9–12.2] | |
6/7 | 7.5 | 10.6 | 7.7 * | 10.4 |
[5.7–10.8] | [8.4–14.2] | [5.1–9.4] | [8.4–14.2] | |
7/7 | ND | 26.2 | 12.2 * | 20.8 |
[11.7–39.4] | [9.0–16.1] | [17.5–25.2] |
Group | Premature Atherosclerosis | IHD | PAD |
---|---|---|---|
(n = 129) | (n = 43) | (n = 69) | |
All | 0.98 | 0.93 * | 0.86 * |
[0.95–1.01] | [0.87–0.99] | [0.81–0.92] | |
Males | 0.94 * | 0.82 * | 0.86 * |
[0.57–0.99] | [0.72–0.93] | [0.79–0.95] | |
Females | 0.97 | 1.02 | 0.86 * |
[0.90–1.05] | [0.95–1.10] | [0.78–0.95] |
Group | Premature Atherosclerosis | IHD | PAD |
---|---|---|---|
(n = 75) | (n = 35) | (n = 67) | |
All | 0.48 * | 0.49 * | 0.56 * |
[0.29–0.82] | [0.25–0.96] | [0.32–0.98] | |
Males | 0.57 | 0.35 * | 0.35 * |
[0.30–1.11] | [0.14–0.88] | [0.16–0.78] | |
Females | 0.39 | 0.83 | 0.75 |
[0.13–1.12] | [0.22–3.2] | [0.33–1.70] |
(a) | ||||
Bilirubin Quartile 1 | Bilirubin Quartile 2 | Bilirubin Quartile 3 | Bilirubin Quartile 4 | |
Bilirubin (μmol/L, min-max) | 2.7–9 | 9.1–12.5 | 12.6–18.6 | 18.9–55.2 |
TAS (mmol/L, median [25–75%) | 1.9 [1.87–1.95] | 1.95 [1.89–2.01] | 1.97 [1.90–2.01] | 1.98 [1.92–2.06] |
p-value | 0.02 | 0.001 | <0.0001 | |
(b) | ||||
Premature Atherosclerosis (n = 129) | IHD (n = 43) | PAD (n = 69) | Controls (n = 225) | |
TAS (mmol/L, median [25–75%]) | 1.34 * [1.24–1.43] | 1.39 * [1.29–1.48] | 1.36 * [1.25–1.5] | 1.94 [1.89–2.01] |
Bilirubin Quartile 1 | Bilirubin Quartile 2 | Bilirubin Quartile 3 | Bilirubin Quartile 4 | |
---|---|---|---|---|
bilirubin (μmol/L, min-max) | 2.7–9.0 | 9.1–12.5 | 12.6–18.6 | 18.9–55.2 |
hsCRP (mg/L, median [25–75%]) | 0.9 (0.30–2.18) | 0.7 (0.23–1.35) | 0.45 (0.20–1.05) | 0.44 (0.20–1.18) |
p-value | NS | 0.012 | 0.01 |
Premature Atherosclerosis | IHD | PAD | Controls | |
---|---|---|---|---|
(n = 129) | (n = 43) | (n = 69) | (n = 225) | |
hsCRP | 1.0 * | 1.3 * | 2.1 * | 0.45 |
[mg/L] | [0.4–2.25] | [0.8–3.3] | [1.05–4.6] | [0.2–1.0] |
TNF-α | 6.9 * | 7.3 * | 7.6 * | 4.4 |
[ng/L] | [4.7–8.5] | [5.8–9.1] | [5.3–10.8] | [3.2–6.1] |
IL-1β | 5.7 * | 9.2 * | 9.5 * | 0.3 |
[ng/L] | [3.5–18.3] | [3.2–17.4] | [5.7–21.7] | [0.13–4.3] |
IL-6 | 3.2 * | 4.2 * | 5.1 * | 0.96 |
[ng/L] | [1.6–9.1] | [2.1–6.9] | [3.2–8.7] | [0.48–2.9] |
IL-8 | 14.1 * | 10.6 | 13.3* | 7.9 |
[ng/L] | [9.6–22.9] | [8–16.7] | [12.1–34.7] | [5.5–11.1] |
IL-10 | 0.29 * | 0.42 * | 0.25 * | 0.98 |
[ng/L] | [0.2–0.4] | [0.3–0.5] | [0.2–0.3] | [0.3–1.6] |
VEGF-A | 413 * | 361 | ND | 234 |
[ng/L] | [272–605] | [171–573] | [170–450] | |
p-selectin | 96 | 80 | 90 | 85 |
[ng/L] | [75–113] | [66–97] | [64–106] | [70–102] |
E-selectin | 40 * | 33 | 33 | 29 |
[ng/L] | [32–47] | [23–41] | [27–43] | [23–37] |
ICAM | 282 * | 258 * | 314 * | 211 |
[ng/L] | [237–371] | [213–298] | [257–380] | [180–244] |
Premature Atherosclerosis | IHD | PAD | Controls | |
---|---|---|---|---|
(n = 129) | (n = 43) | (n = 69) | (n = 225) | |
Age | 44 * | 72 * | 62 * | 39 |
(years) | [40–47] | [68–80] | [49–75] | [30–6] |
Sex (M:F, %) | 76 * | 70 * | 51 | 48 |
Smoking (%) | 89 * | 52 * | 88 * | 15 |
BMI | 27.6 * | 26.9 * | 27.4 * | 24.2 * |
(kg/m2) | [24.5–29.8] | [24.9–29.8] | [24.5–28.7] | [22.4–25.4] |
Glucose | 5.1 * | 5.8 * | 5.8 * | 4.7 |
(mmol/L) | [4.7–5.5] | [5.3–6.8] | [5.3–6.6] | [4.8–5] |
Total cholesterol | 4.23 * | 4.35 * | 4.75 | 5.13 |
(mmol/L) | [3.5–4.9] | [3.8–5] | [4.1–5.7] | [4.4–5.7] |
LDL cholesterol | 2.22 * | 2.45 | 2.7 | 2.77 |
(mmol/L) | [1.7–2.8] | [1.9–3.1] | [2–3.5] | [2.4–3.3] |
HDL cholesterol | 1.1 * | 1.36 * | 1.36 | 1.6 |
(mmol/L) | [1–1.3] | [1.1–1.6] | [1.2–1.6] | [1.3–1.9] |
Triacylglyceroles | 1.71 * | 1.17 | 1.29 | 1.13 |
(mmol/L) | [1.1–2.7] | [1–1.5] | [0.9–1.8] | [0.8–1.5] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Vítek, L.; Jirásková, A.; Malíková, I.; Dostálová, G.; Eremiášová, L.; Danzig, V.; Linhart, A.; Haluzík, M. Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis. Antioxidants 2022, 11, 2118. https://doi.org/10.3390/antiox11112118
Vítek L, Jirásková A, Malíková I, Dostálová G, Eremiášová L, Danzig V, Linhart A, Haluzík M. Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis. Antioxidants. 2022; 11(11):2118. https://doi.org/10.3390/antiox11112118
Chicago/Turabian StyleVítek, Libor, Alena Jirásková, Ivana Malíková, Gabriela Dostálová, Lenka Eremiášová, Vilém Danzig, Aleš Linhart, and Martin Haluzík. 2022. "Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis" Antioxidants 11, no. 11: 2118. https://doi.org/10.3390/antiox11112118