Kronik total oklüzyonlu hastalarda iyi koroner kollateral dolaşımın bağımsız belirteçleri olarak serbest testosteron indeksi ve biyoyararlanabilir testosteron
Yıl 2025,
Cilt: 7 Sayı: 6, 810 - 817, 26.10.2025
Abdullah Yıldırım
,
Mustafa Lütfullah Ardıç
,
Emre Paçacı
,
Aslan Erdoğan
,
Akif Küçükcan
,
Mükremin Coşkun
,
Emre Sezici
,
Fadime Koca
,
Eyüp Özkan
,
Hazar Harbalıoğlu
,
Ömer Genç
,
İbrahim Halil Kurt
Öz
Arka plan: Kronik total oklüzyon (CTO), koroner arter hastalığının klinik olarak önemli bir formunu temsil eder ve bu durumda kollateral dolaşım, miyokard perfüzyonunun korunmasında kritik rol oynar. Testosteronun vasküler fonksiyon ve anjiyogenezi etkileyebileceği öne sürülmüş olsa da, androjenik parametreler ile koroner kollateral gelişim arasındaki ilişki belirsizliğini korumaktadır.
Yöntemler: Bu kesitsel vaka-kontrol çalışmasına koroner anjiyografi ile CTO tanısı konulan 230 erkek hasta dahil edildi. Koroner kollateral dolaşım Rentrop sınıflaması ile değerlendirildi ve iyi (skor 2–3) veya zayıf (skor 0–1) kollateral dolaşım olarak sınıflandırıldı. Serum total testosteron, serbest testosteron, SHBG, dehidroepiandrosteron sülfat (DHEAS) ve dihidrotestosteron (DHT) düzeyleri ölçüldü; biyoyararlanabilir testosteron (BioT) ve serbest testosteron indeksi (FTI) hesaplandı. Androjenik parametreler ile kollateral dolaşım arasındaki ilişkiler korelasyon analizi, lojistik regresyon ve ROC eğrisi analizi ile incelendi.
Bulgular: Çalışma popülasyonunda 142 hastada iyi, 88 hastada zayıf kollateral dolaşım saptandı. İyi kollaterali olan hastalarda total testosteron (p<0.001), DHEAS (p=0.048), BioT (p<0.001), BioT yüzdesi (p<0.001) ve FTI (p<0.001) düzeyleri daha yüksek iken, SHBG düzeyi zayıf kollateral grubunda daha yüksekti (p<0.001). Serbest testosteron ve DHT gruplar arasında farklı değildi. Çok değişkenli lojistik regresyon analizinde BMI (aOR=1.163, %95 GA: 1.044–1.296, p=0.006) ve FTI (aOR=1.573, %95 GA: 1.345–1.841, p<0.001) iyi kollateral dolaşım ile bağımsız olarak ilişkili bulundu. ROC analizi FTI (AUC=0.815, %95 GA: 0.727–0.884, p<0.001) ve BioT’nin (AUC=0.804, %95 GA: 0.715–0.875, p<0.001) güçlü prediktif performans gösterdiğini ortaya koydu; her ikisi de total veya serbest testesterondan daha üstündü.
Sonuç: Serum testosteron ile ilişkili indeksler, özellikle FTI ve BioT, CTO’lu erkek hastalarda iyi koroner kollateral dolaşımın bağımsız belirteçleri olarak öne çıkmaktadır. Bu parametrelerin klinik değerlendirmeye dahil edilmesi, ek prognostik değer sağlayabilir ve tedavi stratejilerinin şekillendirilmesine katkıda bulunabilir.
Kaynakça
-
Schaper W, Scholz D. Factors regulating arteriogenesis. Thromb Vasc Biol. 2003;23(7):1143-1151. doi:10.1161/01.ATV.0000069625.11230.96
-
Werner GS, Ferrari M, Heinke S, et al. Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions. Circulation. 2003; 107(15):1972-1977. doi:10.1161/01.CIR.0000061953.72662.3A
-
Sianos G, Werner GS, Galassi AR, et al. Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club. EuroIntervention. 2012;8(1):139-145. doi:10.4244/EIJV8I1A21
-
Heil M, Schaper W. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res. 2004;95(5): 449-458. doi:10.1161/01.RES.0000141145.78900.44
-
Kirby M, Hackett G, Ramachandran S. Testosterone and the heart. Eur Cardiol. 2019;14(2):103-110. doi:10.15420/ecr.2019.13.1
-
Sarkar M, VanWagner LB, Terry JG, et al. Sex hormone–binding globulin levels in young men are associated with nonalcoholic fatty liver disease in midlife. Official J Am College Gastroenterol ACG. 2019;114(5):758-763.
-
Soleimany A, Kavandi H, Khalili N, et al. The association between serum testosterone levels and coronary artery disease in men. Shiraz E-Med J. 2022;23(8):e116040. doi:10.5812/semj-116040
-
Gururani K, Jose J, George PV. Testosterone as a marker of coronary artery disease severity in middle aged males. Indian Heart J. 2016;68 Suppl 3(Suppl 3):S16-S20. doi:10.1016/j.ihj.2016.07.002
-
Baumgartner H, Hung J, Bermejo J, et al. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017;18(3):254-275. doi:10.1093/ehjci/jew335
-
TIMI Study Group. The thrombolysis in myocardial ınfarction (TIMI) trial. Phase I findings. N Engl J Med. 1985;312(14):932-936. doi:10.1056/NEJM198504043121437
-
Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol. 1985; 5(3):587-592. doi:10.1016/s0735-1097(85)80380-6
-
Magro M, Nauta S, Simsek C, et al. Value of the SYNTAX score in patients treated by primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: the MI SYNTAXscore study. Int J Cardiol Heart Vasc. 2020;30:100643. doi:10.1016/j.ijcha.2020.100643
-
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-3672. doi:10.1210/jcem.84.10.6079
-
Koerselman J, van der Graaf Y, de Jaegere PPT, Grobbee DE. Coronary collaterals: an important and underexposed aspect of coronary artery disease. Circulation. 2003;107(19):2507-2511. doi:10.1161/01.CIR. 0000065118.99409.5F
-
Schaper W, Ito WD. Molecular mechanisms of coronary collateral vessel growth. Circ Res. 1996;79(5):911-919. doi:10.1161/01.res.79.5.911
-
Van Royen N, Piek JJ, Buschmann I, Hoefer I, Voskuil M, Schaper W. Stimulation of arteriogenesis; a new concept for the treatment of arterial occlusive disease. Cardiovasc Res. 2001;49(3):543-553. doi:10.1016/s 0008-6363(00)00206-6
-
Lam YT, Lecce L, Yuen SC, et al. Androgens ameliorate impaired ischemia-induced neovascularization due to aging in male mice. Endocrinology. 2019;160(5):1137-1149. doi:10.1210/en.2018-00951
-
Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation. Microvasc Res. 2010;79(3):200-206. doi:10.1016/j.mvr.2010.01.012
-
Lambiase PD, Edwards RJ, Anthopoulos P, et al. Circulating humoral factors and endothelial progenitor cells in patients with differing coronary collateral support. Circulation. 2004;109(24):2986-2992. doi: 10.1161/01.CIR.0000130639.97284.EC
-
Cao J, Zou H, Zhu BP, et al. Sex hormones and androgen receptor: risk factors of coronary heart disease in elderly men. Chin Med Sci J. 2010; 25(1):44-49. doi:10.1016/s1001-9294(10)60019-3
-
Foresta C, Caretta N, Lana A, et al. Reduced number of circulating endothelial progenitor cells in hypogonadal men. J Clin Endocrinol Metab. 2006;91(11):4599-4602. doi:10.1210/jc.2006-0763
-
Erdoğan A, Çakmak EÖ, Güler A, Kılıçgedik A, Kırma C. The relationship between levels of sex steroids and coronary collateral circulation in men patients with coronary artery disease. Koşuyolu Heart Journal. 2022;25(1):33-39.
-
Webb CM, McNeill JG, Hayward CS, De Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation. 1999;100(16):1690-1696. doi:10.1161/01.cir. 100.16.1690
-
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
-
Sezavar S, Hassanzadeh M, Samadanifard S, Zandi KF. Testosterone, coronary artery disease, and the syntax score in males: a case control study. OA Text. 2018;4:1-4. doi:10.15761/JIC.1000239
-
English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000;21(11):890-894. doi:10.1053/euhj.1999.1873
-
Kabakci G, Yildirir A, Can I, Unsal I, Erbas B. Relationship between endogenous sex hormone levels, lipoproteins and coronary atherosclerosis in men undergoing coronary angiography. Cardiology. 1999;92(4):221-225. doi:10.1159/000006977
-
Allameh F, Pourmand G, Bozorgi A, Nekuie S, Namdari F. The association between androgenic hormone levels and the risk of developing coronary artery disease (CAD). Iran J Public Health. 2016;45(1):14-19.
-
Köprülü D, Taşcanov MB. ST Elevasyonsuz Miyokart enfarktüsü geçiren erkek hastalarda serbest testosteron düzeyi ile koroner arter hastalığının ciddiyeti arasındaki ilişki. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17(1):82-86. doi:10.35440/hutfd.671941
-
Nathan L, Shi W, Dinh H, et al. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc Natl Acad Sci U S A. 2001;98(6):3589-3593. doi:10.1073/pnas.051003698
-
Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994;14(5):701-706. doi:10.1161/01.atv.14.5.701
-
Yang XC, Jing TY, Resnick LM, Phillips GB. Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men. Arterioscler Thromb. 1993;13(4):467-471. doi:10.1161/ 01.atv.13.4.467
-
Zeller T, Appelbaum S, Kuulasmaa K, et al. Predictive value of low testosterone concentrations regarding coronary heart disease and mortality in men and women–evidence from the FINRISK 97 study. J Intern Med. 2019;286(3):317-325. doi:10.1111/joim.12943
-
Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976;38(1):46-51. doi:10.1016/ 0002-9149(76)90061-8
-
Faix JD. Principles and pitfalls of free hormone measurements. Best Pract Res Clin Endocrinol Metab. 2013;27(5):631-645. doi:10.1016/j.beem.2013.06.007
-
Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010;96(22):1821-1825. doi:10.1136/hrt.2010.195412
-
Luo X, Wang Y, Wang L, Shen Y, Ren M. Association between female androgen levels, metabolic syndrome, and cardiovascular disease: an NHANES analysis (2013-2016). Int J Womens Health. 2024;16:2087-2101. doi:10.2147/ijwh.S475149
Free testosterone index and bioavailable testosterone as independent predictors of good coronary collateral circulation in CTO patients
Yıl 2025,
Cilt: 7 Sayı: 6, 810 - 817, 26.10.2025
Abdullah Yıldırım
,
Mustafa Lütfullah Ardıç
,
Emre Paçacı
,
Aslan Erdoğan
,
Akif Küçükcan
,
Mükremin Coşkun
,
Emre Sezici
,
Fadime Koca
,
Eyüp Özkan
,
Hazar Harbalıoğlu
,
Ömer Genç
,
İbrahim Halil Kurt
Öz
Aims: Chronic total occlusion (CTO) represents a clinically important form of coronary artery disease in which collateral circulation plays a critical role in maintaining myocardial perfusion. Although testosterone has been suggested to influence vascular function and angiogenesis, the relationship between androgenic parameters and coronary collateral development remains uncertain.
Methods: This cross-sectional case-control study included 230 male patients diagnosed with CTO by coronary angiography. Coronary collateral circulation was graded using the Rentrop classified categorized as good CCF (score 2–3) or bad CCF (score 0–1). Serum levels of total testosterone, free testosterone, SHBG, dehydroepiandrosterone sulfate (DHEAS), and dihydrotestosterone (DHT) were measured, and bioavailable testosterone (BioT) and free testosterone index (FTI) were calculated. Associations between androgenic parameters and collateral circulation were analyzed using correlation analysis, logistic regression, and ROC curve analysis.
Results: Of the study cohort, 142 patients had good CCF and 88 had bad CCF. Patients with good CCF had higher levels of total testosterone (p<0.001), DHEAS (p=0.048), BioT (p<0.001), BioT percentage (p<0.001), and FTI (p<0.001), whereas SHBG was higher in the bad CCF group (p<0.001). Free testosterone and DHT did not differ between groups. In multivariable logistic regression, BMI (aOR=1.163, 95% CI:1.044 to 1.296, p=0.006) and FTI (aOR=1.573, 95% CI:1.345 to 1.841, p<0.001) were independently associated with good CCF. ROC analysis demonstrated strong predictive performance for FTI (AUC=0.815, 95% CI:0.727 to 0.884, p<0.001) and BioT (AUC=0.804, 95% CI:0.715 to 0.875, p<0.001), both superior to total or free testosterone.
Conclusion: Serum testosterone–related indices, particularly FTI and BioT, emerged as independent predictors of good coronary collateral circulation in male patients with CTO. Incorporating these parameters into clinical evaluation may provide additional prognostic information and help guide therapeutic strategies.
Etik Beyan
The study was initiated with the approval of the Cukurova University Clinical Researches Ethics Committee (Date: 02.10.2020, No: 104-21).
Kaynakça
-
Schaper W, Scholz D. Factors regulating arteriogenesis. Thromb Vasc Biol. 2003;23(7):1143-1151. doi:10.1161/01.ATV.0000069625.11230.96
-
Werner GS, Ferrari M, Heinke S, et al. Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions. Circulation. 2003; 107(15):1972-1977. doi:10.1161/01.CIR.0000061953.72662.3A
-
Sianos G, Werner GS, Galassi AR, et al. Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club. EuroIntervention. 2012;8(1):139-145. doi:10.4244/EIJV8I1A21
-
Heil M, Schaper W. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res. 2004;95(5): 449-458. doi:10.1161/01.RES.0000141145.78900.44
-
Kirby M, Hackett G, Ramachandran S. Testosterone and the heart. Eur Cardiol. 2019;14(2):103-110. doi:10.15420/ecr.2019.13.1
-
Sarkar M, VanWagner LB, Terry JG, et al. Sex hormone–binding globulin levels in young men are associated with nonalcoholic fatty liver disease in midlife. Official J Am College Gastroenterol ACG. 2019;114(5):758-763.
-
Soleimany A, Kavandi H, Khalili N, et al. The association between serum testosterone levels and coronary artery disease in men. Shiraz E-Med J. 2022;23(8):e116040. doi:10.5812/semj-116040
-
Gururani K, Jose J, George PV. Testosterone as a marker of coronary artery disease severity in middle aged males. Indian Heart J. 2016;68 Suppl 3(Suppl 3):S16-S20. doi:10.1016/j.ihj.2016.07.002
-
Baumgartner H, Hung J, Bermejo J, et al. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017;18(3):254-275. doi:10.1093/ehjci/jew335
-
TIMI Study Group. The thrombolysis in myocardial ınfarction (TIMI) trial. Phase I findings. N Engl J Med. 1985;312(14):932-936. doi:10.1056/NEJM198504043121437
-
Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol. 1985; 5(3):587-592. doi:10.1016/s0735-1097(85)80380-6
-
Magro M, Nauta S, Simsek C, et al. Value of the SYNTAX score in patients treated by primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: the MI SYNTAXscore study. Int J Cardiol Heart Vasc. 2020;30:100643. doi:10.1016/j.ijcha.2020.100643
-
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-3672. doi:10.1210/jcem.84.10.6079
-
Koerselman J, van der Graaf Y, de Jaegere PPT, Grobbee DE. Coronary collaterals: an important and underexposed aspect of coronary artery disease. Circulation. 2003;107(19):2507-2511. doi:10.1161/01.CIR. 0000065118.99409.5F
-
Schaper W, Ito WD. Molecular mechanisms of coronary collateral vessel growth. Circ Res. 1996;79(5):911-919. doi:10.1161/01.res.79.5.911
-
Van Royen N, Piek JJ, Buschmann I, Hoefer I, Voskuil M, Schaper W. Stimulation of arteriogenesis; a new concept for the treatment of arterial occlusive disease. Cardiovasc Res. 2001;49(3):543-553. doi:10.1016/s 0008-6363(00)00206-6
-
Lam YT, Lecce L, Yuen SC, et al. Androgens ameliorate impaired ischemia-induced neovascularization due to aging in male mice. Endocrinology. 2019;160(5):1137-1149. doi:10.1210/en.2018-00951
-
Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation. Microvasc Res. 2010;79(3):200-206. doi:10.1016/j.mvr.2010.01.012
-
Lambiase PD, Edwards RJ, Anthopoulos P, et al. Circulating humoral factors and endothelial progenitor cells in patients with differing coronary collateral support. Circulation. 2004;109(24):2986-2992. doi: 10.1161/01.CIR.0000130639.97284.EC
-
Cao J, Zou H, Zhu BP, et al. Sex hormones and androgen receptor: risk factors of coronary heart disease in elderly men. Chin Med Sci J. 2010; 25(1):44-49. doi:10.1016/s1001-9294(10)60019-3
-
Foresta C, Caretta N, Lana A, et al. Reduced number of circulating endothelial progenitor cells in hypogonadal men. J Clin Endocrinol Metab. 2006;91(11):4599-4602. doi:10.1210/jc.2006-0763
-
Erdoğan A, Çakmak EÖ, Güler A, Kılıçgedik A, Kırma C. The relationship between levels of sex steroids and coronary collateral circulation in men patients with coronary artery disease. Koşuyolu Heart Journal. 2022;25(1):33-39.
-
Webb CM, McNeill JG, Hayward CS, De Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation. 1999;100(16):1690-1696. doi:10.1161/01.cir. 100.16.1690
-
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
-
Sezavar S, Hassanzadeh M, Samadanifard S, Zandi KF. Testosterone, coronary artery disease, and the syntax score in males: a case control study. OA Text. 2018;4:1-4. doi:10.15761/JIC.1000239
-
English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000;21(11):890-894. doi:10.1053/euhj.1999.1873
-
Kabakci G, Yildirir A, Can I, Unsal I, Erbas B. Relationship between endogenous sex hormone levels, lipoproteins and coronary atherosclerosis in men undergoing coronary angiography. Cardiology. 1999;92(4):221-225. doi:10.1159/000006977
-
Allameh F, Pourmand G, Bozorgi A, Nekuie S, Namdari F. The association between androgenic hormone levels and the risk of developing coronary artery disease (CAD). Iran J Public Health. 2016;45(1):14-19.
-
Köprülü D, Taşcanov MB. ST Elevasyonsuz Miyokart enfarktüsü geçiren erkek hastalarda serbest testosteron düzeyi ile koroner arter hastalığının ciddiyeti arasındaki ilişki. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17(1):82-86. doi:10.35440/hutfd.671941
-
Nathan L, Shi W, Dinh H, et al. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc Natl Acad Sci U S A. 2001;98(6):3589-3593. doi:10.1073/pnas.051003698
-
Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994;14(5):701-706. doi:10.1161/01.atv.14.5.701
-
Yang XC, Jing TY, Resnick LM, Phillips GB. Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men. Arterioscler Thromb. 1993;13(4):467-471. doi:10.1161/ 01.atv.13.4.467
-
Zeller T, Appelbaum S, Kuulasmaa K, et al. Predictive value of low testosterone concentrations regarding coronary heart disease and mortality in men and women–evidence from the FINRISK 97 study. J Intern Med. 2019;286(3):317-325. doi:10.1111/joim.12943
-
Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976;38(1):46-51. doi:10.1016/ 0002-9149(76)90061-8
-
Faix JD. Principles and pitfalls of free hormone measurements. Best Pract Res Clin Endocrinol Metab. 2013;27(5):631-645. doi:10.1016/j.beem.2013.06.007
-
Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010;96(22):1821-1825. doi:10.1136/hrt.2010.195412
-
Luo X, Wang Y, Wang L, Shen Y, Ren M. Association between female androgen levels, metabolic syndrome, and cardiovascular disease: an NHANES analysis (2013-2016). Int J Womens Health. 2024;16:2087-2101. doi:10.2147/ijwh.S475149