Lipid profile parameters in men with coronary heart disease in different age categories in connection with sex hormone level

Aim of the study was to investigate the main components of the lipid spectrum of blood serum in patients with coronary artery disease, depending on the level of estradiol (E2), testosterone (T) and age.

Material and methods. We examined 161 men aged 35–65 years (median [lower quartile; upper quartile] 53.1 [40.1; 59.4] years) with a history of myocardial infarction more than 30 days before inclusion in the study. Patients were divided into groups by age (35–55 and 56–65 years), as well as according to the content of sex hormones: T ≥ 12 nmol/l and T < 12 nmol/l, E2 ≥ 0.194 nmol/l and E2 < 0.194 nmol/l with double determination.

Results. Of the studied components of the lipid profile, the greatest number of significant changes in men with coronary artery disease in different groups, depending on age and levels of sex steroids, had triglyceride (TG) level. In men aged 35–55 and 56–65 years with hypogonadism, TG concentration was higher compared to peers with normal androgen levels. In the older age group, relatively younger male patients, both when comparing a cohort of men with low T and with its normal values, TG content was also higher. In groups of patients with T level > 12 nmol/l and ≤ 12 nmol, when controlling for height and body weight, there is a statistically significant direct association of age in men of 56–65 years with TG concentration (r = 0.483, p = 0.023 and r = 0.549, p = 0.008, respectively). It was found that in patients with coronary artery disease in the age groups of 35–55 years and 56–65 years with E2 content ≥ 0.194 nmol/l, the TG level was higher than in men with normal estrogen concentration (p = 0.008 and p = 0.033, respectively). In a partial correlation analysis with control of height and body weight in men aged 35–55 years with coronary artery disease, a statistically significant relationship was found between the level of E2  ≥ 0.194 nmol/l and TG content (r = 0.566, p = 0.009), a similar relationship independent of anthropometric parameters was verified and in the older age group (r = 0.316, p = 0.011). In a multivariate analysis, the level of TG was determined by E2 concentration, the other variables under consideration did not statistically significantly affect it.

Conclusions. Hypogonadism in men in each age group studied is associated with elevated TG content. A significant role in the development of hypertriglyceridemia in men is played by hyperestrogenemia in both age groups, being an independent, independent of androgenic status, proatherogenic factor.

1. Shal’nova S.A., Drapkina O.M., Kutsenko V.A., Kapustina A.V., Muromtseva G.A., Jarovaja E.B., Balanova Ju.A., Evstifeeva S.E., Imaeva A.Je., Shljakhto E.V., Bojcov S.A., Astakhova Z.T., Barbarash O.L., Belova O.A., Grinshtejn Ju.I., Efanov A.Ju., Kalachikova O.N., Kulakova N.V., Nedogoda S.V., Rotar’ O.P., Trubacheva I.A., Chernyh T.M. ot imeni uchastnikov issledovanija JeSSE-RF. Infarkt miokarda v populjacii nekotoryh regionov Rossii i ego prognosticheskoe znachenie. Rossiyskiy kardiologicheskiy zhurnal, 2022; 27 (6): 9–19. doi: 10.15829/1560-4071-20224952 (in Russ).

2. Oertelt-Prigione S., Dalibert L., Verdonk P., Stutz E.Z., Klinge I. Implementation Strategies for Gender-Sensitive Public Health Practice: A European Workshop. J. Womens Health (Larchmt), 2017 Nov; 26 (11): 1255–1261. doi: 10.1089/jwh.2017.6592

3. Mali S., Kurosh I., Mohammadi S.M., Sarebanhassanbadi M. Serum free testosterone level in coronary artery disease in candidates for coronary artery bypass graft surgery: A cross-sectional study. Int. J. Reprod Biomed., 2021; 19 (3): 293–302. doi: 10.18502/ijrm.v19i3.8577

4. Tsygankova O.V., Nikolaev K.Yu., Fedorova E.L., Bondareva Z.G., Ragino Yu.I., Platonov D.Yu., Pustovetova M.G. Faktory riska serdechno-sosudistyh zabolevanij. Vzgljad na zhenshhinu. Ateroskleroz, 2014; 10 (1): 44–55 (in Russ).

5. Tsygankova O.V., Nikolaev K.Yu., Fedorova E.L., Bondareva Z.G. Obmen polovyh gormonov v organizme muzhchiny cherez prizmu kardiovaskuljarnogo riska. Ateroskleroz i dislipidemii, 2014; 1 (14): 17–24 (in Russ).

6. Kaur H., Werstuck G.H. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data. CJC Open, 2021 May 17; 3 (10): 1238–1248. doi: 10.1016/j.cjco.2021.05.007

7. Fortini F., Vieceli Dalla Sega F., Caliceti C., Lambertini E., Pannuti A., Peiffer D.S., Balla C., Rizzo P. Estrogen-mediated protection against coronary heart disease: The role of the Notch pathway. J. Steroid. Biochem. Mol. Biol., 2019 May; 189: 87–100. doi: 10.1016/j.jsbmb.2019.02.008

8. El Khoudary S.R., Aggarwal B., Beckie T.M., Hodis H.N., Johnson A.E., Langer R.D., Limacher M.C., Manson J.E., Stefanick M.L., Allison M.A.; American Heart Association Prevention Science Committee of the Council on Epidemiology and Prevention; and Council on Cardiovascular and Stroke Nursing. Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the American Heart Association. Circulation, 2020 Dec 22; 142 (25): e506–e532. doi: 10.1161/CIR.0000000000000912

9. Aljenedil S., Hegele R.A., Genest J., Awan Z. Estrogen-associated severe hypertriglyceridemia with pancreatitis. J. Clin. Lipidol., 2017 Jan-Feb; 11 (1): 297–300. doi: 10.1016/j.jacl.2016.12.006

10. Ueda, Kazutaka & Fukuma, Nobuaki & Adachi, Yusuke & Numata, Genri & Tokiwa, Hiroyuki & Toyoda, Masayuki & Otani, Akira & Hashimoto, Masaki & Liu, Pang-Yen & Takimoto, Eiki. Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System. Frontiers in Physiology, 2021; 12: 738218. doi: 10.3389/fphys.2021.738218

11. Amaya-Montoya M., Pinzón-Cortés J.A., Silva-Bermúdez L.S., Ruiz-Manco D., Pérez-Matos M.C., Jiménez-Mora M.A., Mendivil C.O. ApoE and apoCIII-defined HDL subtypes: a descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity. Lipids Health Dis., 2020 May 25; 19 (1): 106. doi: 10.1186/s12944020-01291-x

12. Wu F.C., von Eckardstein A. Androgens and coronary artery disease. Endocrinol. Rev., 2003; 99 (3): 183– 217.

13. Aryan L., Younessi D., Zargari M., Banerjee S., Agopian J., Rahman S., Borna R., Ruffenach G., Umar S., Eghbali M. The Role of Estrogen Receptors in Cardiovascular Disease. Int. J. Mol. Sci., 2020; 21 (12): 4314. doi: 10.3390/ijms21124314

14. Platonov D.Yu., Kostjuk T.A., Brandt A.I. et al. Kompleksnaja otsenka profilakticheskogo povedenija v otnoshenii serdechno-sosudistykh zabolevanij i faktorov riska ikh razvitija u bol’nykh gipertonicheskoj bolezn’ju i hronicheskoj ishemicheskoj bolezn’ju serdca. Profilakticheskaya meditsina, 2012; 15 (1): 26–31 (in Russ).

15. Pilote L., Karp I. GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary SYndrome). Am. Heart J., 2012; 163 (5): 741–746.

16. Muromceva G.A., Koncevaja A.V., Konstantinov V.V. Rasprostranennost’ faktorov riska neinfektsionnyh zabolevanij v rossijskoj populjatsii v 2012–2013 gg. Rezul’taty issledovanija JeSSE-RF. Kardiovaskuljarnaja terapija i profilaktika, 2014; 6: 4–11. (in Russ).

17. Chung T.H., Kwon Y.J., Lee Y.J. High triglyceride to HDL cholesterol ratio is associated with low testosterone and sex hormone-binding globulin levels in Middle-aged and elderly men. Aging Male, 2020 Jun; 23 (2): 93–97. doi: 10.1080/13685538.2018.1501015

18. Agledahl I., Skjaerpe P.A., Hansen J.B., Svartberg J. Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: the Tromsø study. Nutr. Metab. Cardiovasc. Dis., 2008 May; 18 (4): 256– 262. doi: 10.1016/j.numecd.2007.01.014

19. Feingold K.R. The Effect of Endocrine Disorders on Lipids and Lipoproteins. 2023 Apr 6. In: Feingold K.R., Anawalt B., Blackman M.R., Boyce A., Chrousos G., Corpas E., de Herder W.W., Dhatariya K., Dungan K., Hofland J., Kalra S., Kaltsas G., Kapoor N., Koch C., Kopp P., Korbonits M., Kovacs C.S., Kuohung W., Laferrиre B., Levy M., McGee E.A., McLachlan R., New M., Purnell J., Sahay R., Shah A.S., Singer F., Sperling M.A., Stratakis C.A., Trence D.L., Wilson D.P. (eds.) Endotext [Internet]. South Dartmouth (MA): MDText. com, Inc.; 2000.

20. Srinath R., Gottesman R.F., Golden H.S. et al. Association Between Endogenous Testosterone and Cerebrovascular Disease in the ARIC Study (Atherosclerosis Risk in Communities). Stroke, 2016; 47 (11): 2682–2688.

21. Pospíšilová H., Vaňková M., Hill M., Meloun M., Bendlová B., Dušková M., Stárka L. The differences between aromatizable and non-aromatizable androgens in relation to body composition and metabolic syndrome risk factors in men. J. Steroid. Biochem. Mol. Biol., 2012 Oct; 132 (1-2): 105–111. doi: 10.1016/j.jsbmb.2012.02.005

22. Samaras N., Papadopoulou M.A., Samaras D., Ongaro F. Off-label use of hormones as an antiaging strategy: a review. Clin. Interv. Aging., 2014 Jul 23; 9: 1175–1186. doi: 10.2147/CIA.S48918

23. Kurniawan L.B., Adnan E.; Windarwati; Mulyono B. Insulin resistance and testosterone level in Indonesian young adult males. Rom. J. Intern. Med., 2020 Jun 1; 58 (2): 93–98. doi: 10.2478/rjim-2020-0004

24. Dai W., Ming W., Li Y., Zheng H.Y., Wei C.D., Rui Z., Yan C. Synergistic Effect of a Physiological Ratio of Estradiol and Testosterone in the Treatment of Early-stage Atherosclerosis. Arch. Med. Res., 2015 Nov; 46 (8): 619–629. doi: 10.1016/j.arcmed.2015.11.003

25. Williams G. Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-α and GPER signalling. Mol. Cell. Endocrinol., 2012 Apr 4; 351 (2): 269–278. doi: 10.1016/j.mce.2011.12.017

26. Ohlsson C. Barrett-Connor E. Bhasin S. et al. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MROS (osteoporotic fractures in men) study in Sweden. J. Am. Coll. Cardiol., 2011; 58: 1674–1681.

27. Kusters C.D., Paul K.C., Lu A.T., Ferruci L., Ritz B.R., Binder A.M., Horvath S. Higher testosterone and testosterone/estradiol ratio in men are associated with better epigenetic estimators of mortality risk. medRxiv [Preprint]. 2023 Feb 23; 2023.02.16.23285997. doi: 10.1101/2023.02.16.23285997

28. Apiah D., Luitel S., Nwabuo C.C. et al. Low Endogenous Estradiol Levels Are Associated with Elevated Risk of Cardiovascular Disease Mortality in Young and Middle-Aged Men in the United States. Atherosclerosis, 2022.

29. Laouali N., Brailly-Tabard S., Helmer C. et al. Oestradiol level, oestrogen receptors, and mortality in elderly men: the three-city cohort study. Clin. Endocrinol., 2018; 89: 514–525.

30. Reiner Ž. Are endogenous sex hormones important for atherosclerotic cardiovascular disease risk in men? Atherosclerosis, 2022 Nov; 361: 32–33. doi: 10.1016/j.atherosclerosis.2022.10.011