Evaluation of Klotho Protin Levels in Patient with Heart Disease in The City of Tikrit

Authors

  • Lolawa J. Falah Salah Al-Din Education Directorate, Tikrit Education Department, Iraq

DOI:

https://doi.org/10.51699/cajmns.v7i4.3365

Keywords:

Klotho Protein, Acute Coronary, ELISA

Abstract

This study investigated the relationship between soluble Klotho protein levels and acute coronary syndrome (ACS) in Iraqi patients. Klotho is an anti-aging protein with anti-inflammatory and cardiovascular protective properties, and reduced levels have been linked to several cardiovascular diseases. A case-control study was conducted between November 2023 and March 2024. The study included 120 participants, divided into four groups: healthy controls, patients with unstable angina (UA), ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). Blood samples were collected to measure serum Klotho levels using the ELISA technique, while inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also evaluated. The results showed that serum Klotho levels were significantly lower in all ACS patients than in the healthy control group. Among the ACS subgroups, NSTEMI patients had the lowest Klotho levels. A significant negative correlation was found between Klotho and ESR only in the NSTEMI group, indicating that increased inflammation was associated with decreased Klotho concentrations. No significant relationship was observed between Klotho and CRP or other inflammatory markers in the remaining groups. The findings suggest that reduced Klotho levels are associated with acute coronary syndrome and may reflect increased inflammatory activity. Therefore, Klotho may serve as a promising biomarker for cardiovascular disease severity and progression. However, further large-scale, multicenter studies are recommended to confirm these findings and to investigate the potential therapeutic role of Klotho in patients with cardiovascular diseases.

References

A. M. Katz, Physiology of the Heart. Philadelphia, PA, USA: Lippincott Williams & Wilkins, 2010.

B. Ibanez, S. James, S. Agewall, M. J. Antunes, C. Bucciarelli-Ducci, H. Bueno, et al., “2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC),” European Heart Journal, vol. 39, no. 2, pp. 119–177, 2018.

A. Davies and A. Scott, “Acute coronary syndromes,” in Starting to Read ECGs. Cham, Switzerland: Springer, pp. 141–169, 2015.

C. Puelacher, M. Gugala, P. D. Adamson, A. Shah, A. R. Chapman, A. Anand, et al., “Incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction,” Heart, vol. 105, no. 18, pp. 1423–1431, 2019.

M. G. Khan and H. J. Marriott, “Angina,” in Heart Disease Diagnosis and Therapy: A Practical Approach, pp. 127–174, 2005.

P. Theroux and V. Fuster, “Acute coronary syndromes: Unstable angina and non–Q-wave myocardial infarction,” Circulation, vol. 97, no. 12, pp. 1195–1206, 1998.

Y. Yeghiazarians, J. B. Braunstein, A. Askari, and P. H. Stone, “Unstable angina pectoris,” The New England Journal of Medicine, vol. 342, no. 2, pp. 101–114, 2000.

M. A. Helwani, A. Amin, P. Lavigne, S. Rao, S. Oesterreich, E. Samaha, J. C. Brown, and P. Nagele, “Etiology of acute coronary syndrome after noncardiac surgery,” Anesthesiology, vol. 128, no. 6, pp. 1084–1091, 2018.

A. M. D. Kristensen, M. Pareek, K. H. Kragholm, T. S. G. Sehested, M. H. Olsen, and E. B. Prescott, “Unstable angina as a component of primary composite endpoints in clinical cardiovascular trials: Pros and cons,” Cardiology, 2022.

D. S. Blondheim, M. Kleiner-Shochat, A. Asif, M. Kazatsker, A. Frimerman, R. Abu-Fanne, et al., “Characteristics, management, and outcome of transient ST-elevation versus persistent ST-elevation and non-ST-elevation myocardial infarction,” The American Journal of Cardiology, vol. 121, no. 12, pp. 1449–1455, 2018.

D. M. Larson, K. M. Menssen, S. W. Sharkey, S. Duval, R. S. Schwartz, J. Harris, J. T. Meland, B. T. Unger, and T. D. Henry, “False-positive cardiac catheterization laboratory activation among patients with suspected ST-segment elevation myocardial infarction,” JAMA, vol. 298, no. 23, pp. 2754–2760, 2007.

I. C. Rokos, W. J. French, A. Mattu, G. Nichol, M. E. Farkouh, R. Reiffel, and G. W. Stone, “Appropriate cardiac cath lab activation: Optimizing electrocardiogram interpretation and clinical decision-making for acute ST-elevation myocardial infarction,” American Heart Journal, vol. 160, no. 5, pp. 995–1003.e1–1003.e8, 2010.

A. Deshpande and Y. Birnbaum, “ST-segment elevation: Distinguishing ST-elevation myocardial infarction from ST elevation secondary to nonischemic etiologies,” World Journal of Cardiology, vol. 6, no. 10, p. 1067, 2014.

P. T. O’Gara, F. G. Kushner, D. D. Ascheim, D. E. Casey, M. K. Chung, J. A. de Lemos, et al., “2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Journal of the American College of Cardiology, vol. 61, no. 4, pp. e78–e140, 2013.

K. Szummer, L. Wallentin, L. Lindhagen, J. Alfredsson, D. Erlinge, C. Held, et al., “Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: Experiences from SWEDEHEART registry 1995 to 2014,” European Heart Journal, vol. 39, no. 42, pp. 3766–3776, 2018.

W.-Y. Liang, L.-H. Wang, J.-H. Wei, Q.-L. Li, Q.-Y. Li, Q. Liang, N.-Q. Hu, and L.-H. Li, “No significant association of serum Klotho concentration with blood pressure and pulse wave velocity in a Chinese population,” Scientific Reports, vol. 11, no. 1, 2021.

M. Hall, O. J. Bebb, T. B. Dondo, A. T. Yan, S. G. Goodman, H. Bueno, et al., “Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction,” European Heart Journal, vol. 39, no. 42, pp. 3798–3806, 2018.

X. Han, L. Bai, M. H. Jeong, J. H. Ahn, D. Y. Hyun, K. H. Cho, et al., “Higher long-term mortality in patients with non-ST-elevation myocardial infarction than ST-elevation myocardial infarction after discharge,” Yonsei Medical Journal, vol. 62, no. 5, pp. 400–408, 2021.

K. Tishkowski and V. Gupta, Erythrocyte Sedimentation Rate. Treasure Island, FL, USA: StatPearls Publishing, 2022.

F. Toss, A. Nordström, and P. Nordström, “Inflammation in young adulthood is associated with myocardial infarction later in life,” American Heart Journal, vol. 165, no. 2, pp. 164–169, 2013.

I. Navarro-Millán, S. Yang, S. L. DuVall, L. Chen, J. Baddley, G. W. Cannon, et al., “Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: Data from the National Veterans Health Administration,” Annals of the Rheumatic Diseases, vol. 75, no. 2, pp. 341–347, 2016.

M. Van Toorenburg, V. J. van den Berg, T. van der Ploeg, A. Heestermans, M. Dirksen, R. Hautvast, et al., “Addition of routinely measured blood biomarkers significantly improves GRACE risk stratification in patients with myocardial infarction,” International Journal of Cardiology, vol. 273, pp. 237–242, 2018.

M. Kuro-o, Y. Matsumura, H. Aizawa, H. Kawaguchi, T. Suga, T. Utsugi, et al., “Mutation of the mouse klotho gene leads to a syndrome resembling ageing,” Nature, vol. 390, no. 6655, pp. 45–51, 1997.

J. Xie, S.-K. Cha, S.-W. An, M. Kuro-o, L. Birnbaumer, and C.-L. Huang, “Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart,” Nature Communications, vol. 3, no. 1, Art. no. 1238, 2012.

M. Sopjani, I. Alesutan, M. Dërmaku-Sopjani, S. Gu, C. Zelenak, C. Munoz, et al., “Regulation of the Na+/K+ ATPase by Klotho,” FEBS Letters, vol. 585, no. 12, pp. 1759–1764, 2011.

D. A. Drew, R. Katz, S. Kritchevsky, J. Ix, M. Shlipak, O. M. Gutiérrez, et al., “Association between soluble Klotho and change in kidney function: The Health Aging and Body Composition Study,” Journal of the American Society of Nephrology, vol. 28, no. 6, pp. 1859–1866, 2017.

F. Nie, D. Wu, H. Du, X. Yang, M. Yang, X. Pang, and Y. Xu, “Serum Klotho protein levels and their correlations with the progression of type 2 diabetes mellitus,” Journal of Diabetes and Its Complications, vol. 31, no. 3, pp. 594–598, 2017.

M. Christov, J. A. Neyra, S. Gupta, and D. E. Leaf, “Fibroblast growth factor 23 and Klotho in AKI,” Seminars in Nephrology, vol. 39, no. 1, pp. 57–75, 2019.

F. J. Amaro-Gahete, A. de-la-O, L. Jurado-Fasoli, J. R. Ruiz, M. J. Castillo, and Á. Gutiérrez, “Role of exercise on S-Klotho protein regulation: A systematic review,” Current Aging Science, vol. 11, no. 2, pp. 100–107, 2018.

I. Liguori, G. Russo, F. Curcio, G. Bulli, L. Aran, D. Della-Morte, et al., “Oxidative stress, aging, and diseases,” Clinical Interventions in Aging, vol. 13, pp. 757–772, 2018.

L. Guariguata, D. R. Whiting, I. Hambleton, J. Beagley, U. Linnenkamp, and J. E. Shaw, “Global estimates of diabetes prevalence for 2013 and projections for 2035,” Diabetes Research and Clinical Practice, vol. 103, no. 2, pp. 137–149, 2014.

A. Lopez-Candales, P. M. H. Burgos, D. F. Hernandez-Suarez, and D. Harris, “Linking chronic inflammation with cardiovascular disease: From normal aging to the metabolic syndrome,” Journal of Nature and Science, vol. 3, no. 4, 2017.

H.-C. Pan, K.-M. Chou, C.-C. Lee, N.-I. Yang, and C.-Y. Sun, “Circulating Klotho levels can predict long-term macrovascular outcomes in type 2 diabetic patients,” Atherosclerosis, vol. 276, pp. 83–90, 2018.

H.-Y. Ding and H.-X. Ma, “Significant roles of anti-aging protein Klotho and fibroblast growth factor 23 in cardiovascular disease,” Journal of Geriatric Cardiology, vol. 12, no. 4, pp. 439–447, 2015.

F. J. Amaro-Gahete, L. Jurado-Fasoli, G. Sanchez-Delgado, J. V. García-Lario, M. J. Castillo, and J. R. Ruiz, “Relationship between plasma S-Klotho and cardiometabolic risk in sedentary adults,” Aging (Albany NY), vol. 12, no. 3, pp. 2698–2711, 2020.

N. Keles, M. Caliskan, B. Dogan, N. N. Keles, M. Kalcik, F. Aksu, et al., “Low serum level of Klotho is an early predictor of atherosclerosis,” The Tohoku Journal of Experimental Medicine, vol. 237, no. 1, pp. 17–23, 2015.

K. Nakanishi, M. Nishida, M. Taneike, R. Yamamoto, T. Moriyama, and K. Yamauchi-Takihara, “Serum Klotho levels contribute to the prevention of disease progression,” International Journal of General Medicine, vol. 14, pp. 229–238, 2021.

T. Fulop, A. Larbi, J. M. Witkowski, J. McElhaney, M. Loeb, M. Mitnitski, and G. Pawelec, “Aging, frailty and age-related diseases,” Biogerontology, vol. 11, no. 5, pp. 547–563, 2010.

J.-H. Kim, K.-H. Hwang, K.-S. Park, I. D. Kong, and S.-K. Cha, “Biological role of anti-aging protein Klotho,” Journal of Lifestyle Medicine, vol. 5, no. 1, pp. 1–6, 2015.

K. G. Avin, P. M. Coen, W. Huang, D. B. Stolz, G. A. Sowa, J. J. Dubé, et al., “Skeletal muscle as a regulator of the longevity protein, Klotho,” Frontiers in Physiology, vol. 5, Art. no. 189, 2014.

F. J. Amaro-Gahete, L. Jurado-Fasoli, Á. Gutiérrez, J. R. Ruiz, and M. J. Castillo, “Association of physical activity and fitness with S-Klotho plasma levels in middle-aged sedentary adults: The FIT-AGEING study,” Maturitas, vol. 123, pp. 25–31, 2019.

E. Martín-Núñez, J. Donate-Correa, C. Ferri, Á. López-Castillo, A. Delgado-Molinos, C. Hernández-Carballo, et al., “Association between serum levels of Klotho and inflammatory cytokines in cardiovascular disease: A case-control study,” Aging (Albany NY), vol. 12, no. 2, pp. 1952–1964, 2020.

A. Rosengren, L. Wallentin, M. Simoons, A. K. Gitt, S. Behar, A. Battler, and D. Hasdai, “Age, clinical presentation, and outcome of acute coronary syndromes in the Euro Heart Acute Coronary Syndrome Survey,” European Heart Journal, vol. 27, no. 7, pp. 789–795, 2006.

I. Topchii, P. Semenovykh, T. Shcherban, V. Galchinska, and K. Savicheva, “Serum Klotho protein level in type 2 diabetic patients depending on the renal function,” Ukrainian Journal of Nephrology and Dialysis, no. 3, pp. 60–66, 2020.

Downloads

Published

2026-08-10

How to Cite

Falah, L. J. (2026). Evaluation of Klotho Protin Levels in Patient with Heart Disease in The City of Tikrit. Central Asian Journal of Medical and Natural Science, 7(4), 195–208. https://doi.org/10.51699/cajmns.v7i4.3365

Issue

Section

Articles