The role of elevated monocyte and high-density lipoprotein cholesterol ratio in endothelial dysfunction and cardiovascular risk in acromegaly patients
Abstract
Aims: This study aimed to investigate the role of the monocyte-to-high-density lipoprotein ratio (MHR) as an indicator of endothelial dysfunction and cardiovascular risk in patients with acromegaly.
Methods: The study group consisted of 125 patients diagnosed with acromegaly, while the control group included 123 healthy individuals who visited the endocrine clinic due to pituitary incidentaloma but had no acromegaly diagnosis. Medical and laboratory records of all participants were reviewed retrospectively.
Results: The average MHR in patients with acromegaly was found to be statistically significantly higher than that in the healthy control group. In the acromegaly group, systolic blood pressure, glucose, HbA1c, lipids (total cholesterol, LDL, triglycerides), sedimentation rate, CRP, and neutrophils were significantly higher to the control group. The optimal MHR cutoff for acromegaly was 12.01, with 85.1% sensitivity, 85% specificity, and an AUC of 0.64.
Conclusion: MHR, a potential biomarker considered an indicator of inflammation, was significantly higher in patients with acromegaly compared to the healthy control group. This finding suggests that MHR may serve as a useful marker for assessing cardiovascular risk and endothelial dysfunction in patients with acromegaly.
Ethical Statement
Ethical Approval: This study was approved by the Ethics Committee of Akdeniz University with the Approval No (TBAEK-131 DATE:30.01.2025).
References
- Ren J, Anversa P. The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome. Biochem Pharmacol. 2015;93(4):409-417. doi: 10.1016/j.bcp.2014.12.006
- Colao A. The GH-IGF-I axis and the cardiovascular system: clinical implications. Clin Endocrinol. 2008;69(3):347-358. doi:10.1111/j.1365-2265. 2008.03292.x
- Colao A, Ferone D, Marzullo P, Lombardi G. Systemic compli- cations of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102-152. doi:10.1210/er. 2002-0022
- Melmed S, Casanueva FF, Klibanski A, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013; 16(3):294-302. doi:10.1007/s11102-012-0420-x
- Wolters TLC, Netea MG, Riksen NP, Hermus ARMM, Netea-Maier RT. Acromegaly, inflammation and cardiovascular disease: a review. Rev Endocr Metab Disord. 2020;21(4):547-568. doi:10.1007/s11154-020-09560-x
- Villanueva DLE, Tiongson MD, Ramos JD, Llanes EJ. Monocyte to high-density lipoprotein ratio (MHR) as a predictor of mortality and major adverse cardiovascular events (MACE) among ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention: a meta-analysis. Lipids Health Dis. 2020;19(1):55. doi:10.1186/s12944-020-01242-6
- Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12): 1119-1131. doi:10.1056/NEJMoa1707914
- Higashi Y, Quevedo HC, Tiwari S, et al. Interaction between insulin-like growth factor-1 and atherosclerosis and vascular aging. Front Horm Res. 2014;43:107-124. doi:10.1159/000360571
- Maffei P, Dassie F, Wennberg A, Parolin M, Vettor R. The endothelium in acromegaly. Front Endocrinol (Lausanne). 2019;10:437. doi:10.3389/fendo.2019.00437
- Hong FF, Liang XY, Liu W, et al. Roles of eNOS in atherosclerosis treatment. Inflamm Res. 2019;68(6):429-441. doi:10.1007/s00011-019-01229-9
- Caicedo D, Díaz O, Devesa P, Devesa J. Growth hormone (GH) and cardiovascular system. Int J Mol Sci. 2018;19(1):290. doi:10.3390/ijms 19010290
- Groh L, Keating ST, Joosten LAB, Netea MG, Riksen NP. Monocyte and macrophage immunometabolism in atherosclerosis. Semin Immunopathol. 2018;40(2):203-214. doi:10.1007/s00281-017-0656-7
- Choi SH, Kim JH, Lim S, et al. Monocyte count as a predictor of cardiovascular mortality in older Korean people. Age Ageing. 2017;46(3): 433-438. doi:10.1093/ageing/afw226
- Açıkgöz SK, Açıkgöz E, Şensoy B, Topal S, Aydoğdu S. Monocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in ST-segment elevation myocardial infarction. Cardiol J. 2016;23(5):505-512. doi:10.5603/CJ.a2016.0026
- Cetin MS, Ozcan Cetin EH, Kalender E, et al. Monocyte to HDL cholesterol ratio predicts coronary artery disease severity and future major cardiovascular adverse events in acute coronary syndrome. Heart Lung Circ. 2016;25(11):1077-1086. doi:10.1016/j.hlc.2016.02.023
- Karatas A, Turkmen E, Erdem E, Dugeroglu H, Kaya Y. Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy. Biomark Med. 2018;12(9):953-959. doi:10.2217/bmm-2018-0048
- Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24(6):1468-1474. doi:10.1016/0735-1097(94)90141-4
- Paulus WJ. Unfolding discoveries in heart failure. N Engl J Med. 2020; 382(7):679-682. doi:10.1056/NEJMcibr1913825
- Ronconi V, Giacchetti G, Mariniello B, et al. Reduced nitric oxide levels in acromegaly: cardiovascular implications. Blood Press. 2005;14(4):227-232. doi:10.1080/08037050510034293
- Soeki T, Sata M. Inflammatory biomarkers and atherosclerosis. Int Heart J. 2016;57(2):134-139. doi:10.1536/ihj.15-346
- Ridker PM. From C-reactive protein to Interleukin-6 to Interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res. 2016;118(1):145-156. doi:10.1161/CIRCRESAHA.115.306656
- Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013;13(10):709-721. doi:10.1038/nri3520
- Vacek TP, Rehman S, Neamtu D, Yu S, Givimani S, Tyagi SC. Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms. Vasc Health Risk Manag. 2015;11:173-183. doi:10.2147/ VHRM.S68415
- Brown RA, Shantsila E, Varma C, Lip GY. Current understanding of atherogenesis. Am J Med. 2017;130(3):268-282. doi:10.1016/j.amjmed.2016.10.022
- Boero L, Manavela M, Gomez Rosso L, et al. Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly. Clin Endocrinol. 2009;70(1):88-95. doi:10.1111/j.1365-2265.2008.03323.x
- Boero L, Manavela M, Merono T, Maidana P, Gomez Rosso L, Brites F. GH levels and insulin sensitivity are differently associated with biomarkers of cardiovascular disease in active acromegaly. Clin Endocrinol. 2012;77(4):579-585. doi:10.1111/j.1365-2265.2012.04414.x
- Ueland T, Fougner SL, Godang K, et al. Associations between body composition, circulating interleukin-1 receptor antagonist, osteocalcin, and insulin metabolism in active acromegaly. J Clin Endocrinol Metab. 2010;95(1):361-368. doi:10.1210/jc.2009-0422
- Sodhi A, Tripathi A. Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophages in vitro: involvement of p-38 MAP kinase, STAT3 and NF-kappaB. Cytokine. 2008;41(2):162-173. doi:10. 1016/j.cyto.2007.11.007
- CDC, Adult BMI calculator 2020. https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/english_bmi_calculator/bmi_calculator.html (Accessed 21/04/2021 2021).
- Meidert AS, Saugel B. Techniques for non-invasive monitoring of arterial blood pressure. Front Med (Lausanne). 2018;4:231. doi:10.3389/fmed.2017.00231
- D’Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham heart study. Circulation. 2008;117(6):743-753. doi:10.1161/CIRCULATIONAHA.107.699579
- Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11): 3933-3951. doi:10.1210/jc.2014-2700
- Ganjali S, Gotto AM Jr, Ruscica M, et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018;233(12):9237-9246. doi:10.1002/jcp.27028
- Selcuk M, Yildirim E, Saylik F. Comparison of monocyte with high density lipoprotein cholesterol ratio in dipper and nondipper hypertensive patients. Biomark Med. 2019;13(15):1289-1296. doi:10.2217/ bmm-2019-0062
- Kaplan IG, Kaplan M, Abacioglu OO, Yavuz F, Saler T. Monocyte/HDL ratio predicts hypertensive complications. Bratisl Lek Listy. 2020;121(2): 133-136. doi:10.4149/BLL_2020_018
- Gökçay Canpolat A, Emral R, Keskin Ç, Canlar Ş, Şahin M, Çorapçioğlu D. Association of monocyte-to-high density lipoprotein-cholesterol ratio with peripheral neuropathy in patients with type II diabetes mellitus. Biomark Med. 2019;13(11):907-915. doi:10.2217/bmm-2018-0451
- Onalan E. The relationship between monocyte to high-density lipoprotein cholesterol ratio and diabetic nephropathy. Pak J Med Sci. 2019;35(4): 1081-1086. doi:10.12669/pjms.35.4.534
Akromegali hastalarında yükselmiş monosit ve yüksek yoğunluklu lipoprotein kolesterol oranının endotel disfonksiyonu ve kardiyovasküler risk üzerindeki rolü
Abstract
Amaç:
Bu çalışma, akromegali hastalarında monosit/yüksek dansiteli lipoprotein oranının (MHR) endotel disfonksiyonu ve kardiyovasküler risk üzerindeki rolünü incelemeyi amaçlamıştır.
Yöntem:
Çalışma grubu, akromegali tanısı almış 125 hastadan, kontrol grubu ise hipofizer insidentoloma nedeniyle endokrin kliniğine başvuran ancak akromegali tanısı olmayan 123 sağlıklı bireyden oluşmuştur. Tüm katılımcıların medikal ve laboratuvar kayıtları retrospektif olarak incelenmiştir.
Bulgular:
Akromegali hastalarında ortalama MHR, sağlıklı kontrol grubuna kıyasla istatistiksel olarak anlamlı derecede yüksek bulunmuştur. Akromegali grubunda, sistolik kan basıncı, glikoz, HbA1c, lipitler (toplam kolesterol, LDL, trigliseritler), sedimentasyon hızı, CRP ve nötrofiller kontrol grubuna kıyasla anlamlı olarak daha yüksekti. Akromegali için optimal MHR cutoff değeri 12.01 olup, %85,1 sensitivity, %85 specificity ve 0.64 AUC değerine sahipti.
Sonuç:
Enflamasyonun bir göstergesi olarak kabul edilen potansiyel bir biyobelirteç olan MHR, akromegali hastalarında sağlıklı gruba kıyasla anlamlı derecede yüksek bulunmuştur. Bu durum, MHR'nin akromegali hastalarında kardiyovasküler risk ve endotel disfonksiyonunu değerlendirmede yararlı bir gösterge olabileceğini düşündürmektedir.
References
- Ren J, Anversa P. The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome. Biochem Pharmacol. 2015;93(4):409-417. doi: 10.1016/j.bcp.2014.12.006
- Colao A. The GH-IGF-I axis and the cardiovascular system: clinical implications. Clin Endocrinol. 2008;69(3):347-358. doi:10.1111/j.1365-2265. 2008.03292.x
- Colao A, Ferone D, Marzullo P, Lombardi G. Systemic compli- cations of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102-152. doi:10.1210/er. 2002-0022
- Melmed S, Casanueva FF, Klibanski A, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013; 16(3):294-302. doi:10.1007/s11102-012-0420-x
- Wolters TLC, Netea MG, Riksen NP, Hermus ARMM, Netea-Maier RT. Acromegaly, inflammation and cardiovascular disease: a review. Rev Endocr Metab Disord. 2020;21(4):547-568. doi:10.1007/s11154-020-09560-x
- Villanueva DLE, Tiongson MD, Ramos JD, Llanes EJ. Monocyte to high-density lipoprotein ratio (MHR) as a predictor of mortality and major adverse cardiovascular events (MACE) among ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention: a meta-analysis. Lipids Health Dis. 2020;19(1):55. doi:10.1186/s12944-020-01242-6
- Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12): 1119-1131. doi:10.1056/NEJMoa1707914
- Higashi Y, Quevedo HC, Tiwari S, et al. Interaction between insulin-like growth factor-1 and atherosclerosis and vascular aging. Front Horm Res. 2014;43:107-124. doi:10.1159/000360571
- Maffei P, Dassie F, Wennberg A, Parolin M, Vettor R. The endothelium in acromegaly. Front Endocrinol (Lausanne). 2019;10:437. doi:10.3389/fendo.2019.00437
- Hong FF, Liang XY, Liu W, et al. Roles of eNOS in atherosclerosis treatment. Inflamm Res. 2019;68(6):429-441. doi:10.1007/s00011-019-01229-9
- Caicedo D, Díaz O, Devesa P, Devesa J. Growth hormone (GH) and cardiovascular system. Int J Mol Sci. 2018;19(1):290. doi:10.3390/ijms 19010290
- Groh L, Keating ST, Joosten LAB, Netea MG, Riksen NP. Monocyte and macrophage immunometabolism in atherosclerosis. Semin Immunopathol. 2018;40(2):203-214. doi:10.1007/s00281-017-0656-7
- Choi SH, Kim JH, Lim S, et al. Monocyte count as a predictor of cardiovascular mortality in older Korean people. Age Ageing. 2017;46(3): 433-438. doi:10.1093/ageing/afw226
- Açıkgöz SK, Açıkgöz E, Şensoy B, Topal S, Aydoğdu S. Monocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in ST-segment elevation myocardial infarction. Cardiol J. 2016;23(5):505-512. doi:10.5603/CJ.a2016.0026
- Cetin MS, Ozcan Cetin EH, Kalender E, et al. Monocyte to HDL cholesterol ratio predicts coronary artery disease severity and future major cardiovascular adverse events in acute coronary syndrome. Heart Lung Circ. 2016;25(11):1077-1086. doi:10.1016/j.hlc.2016.02.023
- Karatas A, Turkmen E, Erdem E, Dugeroglu H, Kaya Y. Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy. Biomark Med. 2018;12(9):953-959. doi:10.2217/bmm-2018-0048
- Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24(6):1468-1474. doi:10.1016/0735-1097(94)90141-4
- Paulus WJ. Unfolding discoveries in heart failure. N Engl J Med. 2020; 382(7):679-682. doi:10.1056/NEJMcibr1913825
- Ronconi V, Giacchetti G, Mariniello B, et al. Reduced nitric oxide levels in acromegaly: cardiovascular implications. Blood Press. 2005;14(4):227-232. doi:10.1080/08037050510034293
- Soeki T, Sata M. Inflammatory biomarkers and atherosclerosis. Int Heart J. 2016;57(2):134-139. doi:10.1536/ihj.15-346
- Ridker PM. From C-reactive protein to Interleukin-6 to Interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res. 2016;118(1):145-156. doi:10.1161/CIRCRESAHA.115.306656
- Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013;13(10):709-721. doi:10.1038/nri3520
- Vacek TP, Rehman S, Neamtu D, Yu S, Givimani S, Tyagi SC. Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms. Vasc Health Risk Manag. 2015;11:173-183. doi:10.2147/ VHRM.S68415
- Brown RA, Shantsila E, Varma C, Lip GY. Current understanding of atherogenesis. Am J Med. 2017;130(3):268-282. doi:10.1016/j.amjmed.2016.10.022
- Boero L, Manavela M, Gomez Rosso L, et al. Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly. Clin Endocrinol. 2009;70(1):88-95. doi:10.1111/j.1365-2265.2008.03323.x
- Boero L, Manavela M, Merono T, Maidana P, Gomez Rosso L, Brites F. GH levels and insulin sensitivity are differently associated with biomarkers of cardiovascular disease in active acromegaly. Clin Endocrinol. 2012;77(4):579-585. doi:10.1111/j.1365-2265.2012.04414.x
- Ueland T, Fougner SL, Godang K, et al. Associations between body composition, circulating interleukin-1 receptor antagonist, osteocalcin, and insulin metabolism in active acromegaly. J Clin Endocrinol Metab. 2010;95(1):361-368. doi:10.1210/jc.2009-0422
- Sodhi A, Tripathi A. Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophages in vitro: involvement of p-38 MAP kinase, STAT3 and NF-kappaB. Cytokine. 2008;41(2):162-173. doi:10. 1016/j.cyto.2007.11.007
- CDC, Adult BMI calculator 2020. https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/english_bmi_calculator/bmi_calculator.html (Accessed 21/04/2021 2021).
- Meidert AS, Saugel B. Techniques for non-invasive monitoring of arterial blood pressure. Front Med (Lausanne). 2018;4:231. doi:10.3389/fmed.2017.00231
- D’Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham heart study. Circulation. 2008;117(6):743-753. doi:10.1161/CIRCULATIONAHA.107.699579
- Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11): 3933-3951. doi:10.1210/jc.2014-2700
- Ganjali S, Gotto AM Jr, Ruscica M, et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018;233(12):9237-9246. doi:10.1002/jcp.27028
- Selcuk M, Yildirim E, Saylik F. Comparison of monocyte with high density lipoprotein cholesterol ratio in dipper and nondipper hypertensive patients. Biomark Med. 2019;13(15):1289-1296. doi:10.2217/ bmm-2019-0062
- Kaplan IG, Kaplan M, Abacioglu OO, Yavuz F, Saler T. Monocyte/HDL ratio predicts hypertensive complications. Bratisl Lek Listy. 2020;121(2): 133-136. doi:10.4149/BLL_2020_018
- Gökçay Canpolat A, Emral R, Keskin Ç, Canlar Ş, Şahin M, Çorapçioğlu D. Association of monocyte-to-high density lipoprotein-cholesterol ratio with peripheral neuropathy in patients with type II diabetes mellitus. Biomark Med. 2019;13(11):907-915. doi:10.2217/bmm-2018-0451
- Onalan E. The relationship between monocyte to high-density lipoprotein cholesterol ratio and diabetic nephropathy. Pak J Med Sci. 2019;35(4): 1081-1086. doi:10.12669/pjms.35.4.534
Details
| Primary Language | English |
|---|---|
| Subjects | Endocrinology |
| Journal Section | Original Article |
| Authors | |
| Publication Date | May 30, 2025 |
| Submission Date | April 1, 2025 |
| Acceptance Date | April 24, 2025 |
| Published in Issue | Year 2025 Volume: 8 Issue: 3 |
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