Синдром поликистозных яичников и кардиоваскулярный риск


https://doi.org/10.18705/1607-419X-2018-24-6-654-665

Полный текст:


Аннотация

Синдром поликистозных яичников (СПКЯ) является частным эндокринным заболеванием у женщин репродуктивного возраста. Помимо гиперандрогенемии, нарушений овуляции и фертильности, СПКЯ ассоциирован с повышением частоты выявления таких факторов риска кардиоваскулярных болезней, как ожирение, инсулинорезистентность, нарушенная толерантность к глюкозе, сахарный диабет 2-го типа, артериальная гипертензия и синдром обструктивного апноэ во время сна. Начальные стадии атеросклеротического процесса также хорошо документированы у женщин с СПКЯ. Однако данные проспективных исследований, касающихся конечных точек кардиоваскулярной заболеваемости и смертности, являются скудными и противоречивыми. Возможно, это связано с тем, что СПКЯ представляет собой гетерогенную группу эндокринных, метаболических и репродуктивных нарушений, и разные авторы объединяют в синдром различные совокупности этих нарушений. Разные фенотипы СПКЯ могут быть ассоциированы с разным кардиоваскулярным риском. Максимально он выражен у женщин с «полным» фенотипом (сочетанием всех трех диагностических критериев СПКЯ) и с преобладанием гиперандрогенемии. По данным ряда исследований, основной вклад в повышение риска развития сахарного диабета 2-го типа вносит ожирение, которое выявляется более чем у половины женщин с СПКЯ. Несмотря на слабость доказательной базы в отношении связи СПКЯ с кардиоваскулярной заболеваемостью и смертностью, большинство международных организаций рекомендуют активно выявлять факторы кардиоваскулярного риска у женщин с СПКЯ.

Об авторах

П. В. Попова
Федеральное государственное бюджетное учреждение  «Национальный медицинский исследовательский центр  имени В. А. Алмазова» Министерства здравоохранения  Российской Федерации.
Россия

Попова Полина Викторовна — кандидат медицинских наук, заведующая научно-исследовательской лабораторией эндокринных заболеваний у беременных Института эндокринологии. 

ул. Аккуратова, д. 2, Санкт-Петербург, 197341.



И. В. Горелова
Федеральное государственное бюджетное учреждение  «Национальный медицинский исследовательский центр  имени В. А. Алмазова» Министерства здравоохранения  Российской Федерации.
Россия
Горелова Инга Вадимовна — кандидат медицинских наук, заведующая научно-исследовательской лабораторией репродуктивных технологий Института перинатологии и педиатрии.


Е. В. Гринева
Федеральное государственное бюджетное учреждение  «Национальный медицинский исследовательский центр  имени В. А. Алмазова» Министерства здравоохранения  Российской Федерации.
Россия
Гринева Елена Николаевна — доктор медицинских наук, профессор, директор Института эндокринологии.


Список литературы

1. Bozdag G, Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841–2855.

2. Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36(5):487–525.

3. Teede H, Misso M, Costello M, Dokras A, Laven J, Moran L et al. International evidence based guideline for the assessment and management of polycystic ovary syndrome. Clin Endocrinol. 2018;89(3):251–268.

4. Godas VT, Dumesic DA. Polycystic ovary syndrome. Endocrinol Metab Clin North Am. 1997;26(4):893–912.

5. Barbieri RL, Makris A, Randell RW, Daniels G, Kistner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab. 1986;62(5):904–910.

6. Franks S, Gilling-Smith C, Watson H, Willis D. Polycystic ovary syndrome. Insulin function in the normal and polycystic ovary. Endocrinol Metab Clin North Am. 1999;28(2):362–378.

7. Legro RS. Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr Rew. 2003;24(3):302–312. doi:10.1210/er.2003-0004

8. Zawedzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR eds. Polycystic ovary syndrome. Boston: Blackwell Scientific. 1992. 377–384 p.

9. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25. PMID:14711538.

10. Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assess- ment of polycystic ovary syndrome: international consensus definitions. Hum Reprod Update. 2003;9(6):505–514. PMID:14714587.

11. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–4592. doi:10.1210/ jc.2013-2350

12. Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar- Morreale HF, Franks S, Gambineri A. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol. 2014;171(4): P1-P29. doi:10.1530/ EJE-14–0253

13. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists, American College or Endocrinology and Androgen Excess and PCOS Society Disease State Clinical Review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome. Endocr Pract. 2015;21(11):1291–1300. doi:10.4158/ EP15748.DSCPT2

14. Carmina E, Chu MC, Longo RA, Rini GB, Lobo RA. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab. 2005;90(5):2545–2549. doi:10.1210/ jc.2004–2279

15. O’Brien RF, Emans SJ. Polycystic ovary syndrome in adolescents. J Pediatr Adolesc Gynecol. 2008;21(3):119–128

16. Glintborg D, Rubin KH, Nybo M, Abrahamsen B, Andersen M. Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome. Cardiovasc Diabetol. 2018;17(1):37. doi:10.1186/s12933-018-0680-5

17. Pasquali R, Casimirri F. The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women. Clin Endocrinol. 1993;39(1):1–16

18. Solomon CG, Hu FB, Dunaif A, Rich-Edwards JE, Stampfer MJ, Willett WC et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab. 2002;87(5):2013–2017. doi:10.1210/jcem.87.5.8471

19. Wang ET, Cirillo PM, Vittinghoff E, Bibbins-Domingo K, Cohn BA, Cedars MI. Menstrual irregularity and cardiovascular mortality. J Clin Endocrinol Metab. 2011;96(1): E114-E118. doi:10.1210/jc.2010-1709

20. Ding DC, Tsai IJ, Wang JH, Lin SZ, Sung FC. Coronary artery disease risk in young women with polycystic ovary syndrome. Oncotarget. 2018;9(9):8756–8764. doi:10.18632/ oncotarget.23985

21. Cibula D, Cifkova R, Fanta M, Poledne R, Zivny J, Skibová J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a

22. Talbott EO, Zborowski JV, Boudreaux MY. Do women with polycystic ovary syndrome have an increased risk of cardiovascular disease? Review of the evidence. Minerva Ginecol. 2004;56(1):27– 39. doi:10.5812/ijem.4020

23. Birdsall MA, Farquhar CM, White HD. Association between polycystic ovary syndrome and extent of coronary artery disease in women having cardiac catheterization. Ann Intern Med. 1997;126(1):32–35.

24. Pierpoint T, McKeigue PM, Isaacs AJ, Wild SH, Jacobs HS. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol. 1998;51(7):581–586.

25. Wild SH, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol. 2000;52 (5):595–600.

26. de Groot PCM, Dekkers OM, Romijn JA, Dieben SWM, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reproduction Update. 2011;17(4):495–500. doi:10.1093/ humupd/dmr001

27. Heida KY, Bots ML, de Groot CJM, van Dunne FM, Hammoud NM et al. Cardiovascular risk management after reproductive and pregnancy-related disorders: A Dutch multidisciplinary evidence-based guideline. Eur J Prev Cardiol, 2016;23(17):1863–1879. doi:10.1177/2047487316659573

28. Gambieri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obesity. 2002; 26(7):883–896. doi:10.1038/sj.ijo.0801994

29. Cattrall FR, Healy DL. Long-term metabolic, cardiovascular and neoplastic risks with polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):803–812. doi:10.1016/j. bpobgyn.2004.05.005

30. Pasquali R, Antenucci D, Casimirri F, Venturoli S, Paradisi R, Fabbri R et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab. 1989;68(1):173–179. doi:10.1210/ jcem-68–1-173

31. Barber TM, Golding SJ, Alvey C, Wass JA, Karpe F, Franks S et al. Global adiposity rather than abnormal region fat distribution characterizes women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93(3):999–1004. doi:10.1210/jc. 2007-2117

32. Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab, 2008;93(1):162–168. doi:10.1210/jc.2007-1834

33. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774–800. doi:10.1210/edrv.18.6.0318

34. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38(9):1165–1174.

35. Orio Jr F, Palomba S, Spinelli L, Cascella T, Tauchmanovà L, Zullo F et al. The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study. J Clin Endocrinol Metab. 2004;89(8):3696– 3701. doi:10.1210/jc.2003–032049

36. Meyer C, McGrath BP, Teede HJ. Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. 2005;90(10):5711–5716. doi:10.1210/jc. 2005–0011

37. Cosma M, Swiglo BA, Flynn DN, Kurtz DM, Labella ML, Mullan RJ et al. Insulin sensitizers for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. J Clin Endocrinol Metab. 2008;93(4):1135–1142. doi:10.1210/jc. 2007–2429

38. Moghetti P, Tosi F, Bonin C, Di Sarra D, Fiers T, Kaufman JM et al. Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2013;98(4): E628-E637. doi:10.1210/jc.2012–3908

39. Moran L, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and metaanalysis. Hum Reprod Update. 2010;16(4): 347–363. doi: 10.1093/ humupd/dmq001

40. Rubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. Development and risk factors of type 2 diabetes in a nationwide population of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102(10):3848–3857. doi:10.1210/jc.2017–01354

41. Pelanis R, Mellembakken JR, Sundström-Poromaa I, Ravn P, Morin-Papunen L, Tapanainen JS. The prevalence of type 2 diabetes is not increased in normal-weight women with PCOS. Human reproduction. 2017;32(11):1–8. doi:10.1093/ humrep/dex294

42. Ollila ME, West S, Keinänen-Kiukaanniemi S, Joke- lainen J, Auvinen J, Puukka K. Overweight and obese but not normal weight women with PCOS are at increased risk of type 2 diabetes mellitus-a prospective, population-based cohort study. Hum Reprod. 2017;32(2):423–431. doi:10.1093/humrep/dew329

43. Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dislipidemia in women with polycystic ovary syndrome. Am J Med. 2001;111(8):607–613.

44. Taponen S, Martikainen H, Jarvelin MR. Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study. J Clin Endocrinol Metab. 2004;89 (5):2114–2118. doi:10.1210/jc.2003–031720

45. Попова П. В., Баранова Е. В., Гринева Е. Н. Распространенность сердечно-сосудистых заболеваний и сахарного диабета тип 2 у женщин перименопаузального возраста с синдромом поликистозных яичников в анамнезе. Артериальная гипертензия. 2009;15(2):218–222. [Popova PV, Baranova EV, Grineva EN. Prevalence of cardiovascular diseases and type 2 diabetes mellitus in perimenopausal women with a history of the polycystic ovary syndrome. Arterial’naya Gipertenziya = Arterial Hypertension. 2009;15(2);218–222. In Russian].

46. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120 (16):1640–1645.

47. Laakso M & Kuusisto J. Insulin resistance and hyperglycaemia in cardiovascular disease development. Nature Rev Endocrinol. 2014;10:293–302.

48. Bil E, Dilbaz B, Cirik DA, Ozelci R, Ozkaya E, Dilbaz S. Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype. J Obstet Gynaecol Res. 2016;42(7):837–843.

49. Helvaci N, Karabulut E, Demir AU, Yildiz BO. Polycystic ovary syndrome and the risk of obstructive sleep apnea: a metaanalysis and review of the literature. Endocr Connect. 2017;6 (7):437–445. doi:10.1530/EC-17–0129

50. Fernandez RC, Moore VM, Van Ryswyk EM, Varcoe TJ, Rodgers RJ, March WA et al. Sleep disturbances in women with polycystic ovary syndrome: prevalence, pathophysiology, impact and management strategies. Nat Sci Sleep. 2018;10:45–64. doi:10.2147/ NSS.S127475

51. Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J. 2006;28(3):596–602. doi:10.1183/09031936.06.00 107805

52. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–1384. doi:10.1056/ NEJM200005113421901

53. Punjabi NM, Polotsky VY. Disorders of glucose metabolism in sleep apnea. J Appl Physiol. 2005;99(5):1998–2007. doi:10.1152/japplphysiol.00695.2005

54. Tasali E, Chapotot F, Leproult R, Whitmore H, Ehrmann DA. Treatment of obstructive sleep apnea improves cardiometabolic function in young obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2011;96(2):365–374. doi: 10.1210/jc.20101187

55. Pugliese D, Nicoletti G, Andreula C, Ciccone M, Triggiani G. Combined protein C deficiency and protein C activated resistance as a cause of caval, peripheral, and cerebral venous thrombosis — a case report. Angiology. 1998;49(5):399–401.

56. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107(3):363–369.

57. Oh JY, Lee JA, Lee H, Oh JY, Sung YA, Chung H. Serum C-reactive protein levels in normal-weight polycystic ovary syndrome. Korean J Intern Med. 2009;24(4):350–355.

58. Möhlig M, Spranger J, Osterhoff M, Ristow M, Pfeiffer AF, Schill T et al. The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol. 2004;150(4):525–532.

59. Yarali H, Yildirir A, Aybar F, Kabakçi G, Bükülmez O, Akgül E et al. Diastolic dysfunction and increased serum homo- cysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome. Fertil Steril. 2001; 76(3):511–516.

60. Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod. 2003;18(4):721–727.

61. Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine levels are increased in polycystic ovary syndrome. Gynecol Obstet Invest. 2002;53(3): 157–162.

62. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRMSponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28–38.

63. Kumarendran B, O’Reilly MW, Manolopoulos KN, Toulis KA, Gokhale KM, Sitch AJ et al. Polycystic ovary synd- rome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: a longitudinal study based on a United Kingdom primary care database. PLoS Medicine. 2018;15(3):e1002542.

64. Shi Y, Zhao H, Shi Y, Cao Y, Yang D, Li Z et al. Genomewide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet. 2012;44(9):1020–1025. doi:10.1038/ ng. 2384

65. Day FR, Hinds DA, Tung JY, Stolk L, Styrkarsdottir U, Saxena R et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun. 2015;6:8464. doi:10.1038/ncomms9464

66. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361(12):1152–1163. doi:10.1056/ NEJMoa0804381

67. Baldani D, Skrgatic L, Cerne J, Oguic S, Gersak B, Gersak K. Association between serum levels and pentanucleotide polymorphism in the sex hormone binding globulin gene and cardiovascular risk factors in females with polycystic ovary syndrome. Mol Med Rep. 2014;11(5):3941–3947.

68. Sales M, Sóter M, Candido A, Fernandes AP, Oliveira FR, Ferreira AC et al. Correlation between plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphism and metabolic/ proinflammatory factors in polycystic ovary syndrome. Gynecol Endocrinol. 2013;29(10):936–939. doi:org/10.3109/09513590.2 013.819086

69. Jones MR, Chua AK, Mengesha EA, Taylor KD, Chen YD, Li X et al. Reproductive Medicine Network & Legro RS. Metabolic and cardiovascular genes in polycystic ovary syndrome: a candidate-wide association study (CWAS). Steroids. 2012;77(4):317–322. doi:org/ 10.1016/j.steroids.2011.12.005

70. Wild RA, Grubb B, Hartz A, Van Nort JJ, Bachman W, Bartholomew M. Clinical signs of androgen excess as risk factors for coronary artery disease. Fertil Steril. 1990;54(2):255–259.

71. Dokras A. Cardiovascular disease risk in women with PCOS. Steroids. 2013;78(8):773–776.

72. Sprung VS, Atkinson G, Cuthbertson DJ, Pugh CJ, Aziz N, Green DJ et al. Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies. Clin Endocrinol. 2013;78(3):438–446.

73. Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001;103(10):1410–1415.

74. Kravariti M, Naka KK, Kalantaridou SN, Kazakos N, Katsouras CS, Makrigiannakis A et al. Predictors of endothelial dysfunction in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(9):5088–5095.

75. Meyer ML, Malek AM, Wild RA, Korytkowski MT, Talbott EO. Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(2):112–126.

76. Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol. 2000;36(4):1253–1260.

77. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(6):2562–2568.

78. Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(11):5454–5461. doi:10.1210/jc.2003032237

79. Chang AY, Ayers C, Minhajuddin A, Jain T, Nurenberg P, de Lemos JA et al. Polycystic ovarian syndrome and subclinical atherosclerosis among women of reproductive age in the Dallas heart study. Clin Endocrinol. 2011;74(1):89–96. doi:10.1111/ j.1365–2265.2010.03907.x

80. Calderon-Margalit R, Siscovick D, Merkin SS, Wang E, Daviglus ML, Schreiner PJ et al. Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the Coronary Artery Risk Development in Young Adults Women’s study. Arterioscler Thromb Vasc Biol. 2014;34(12):2688–2694.

81. Синдром поликистозных яичников в репродуктивном возрасте (современные подходы к диагностике и лечению). Клинические рекомендации (протокол лечения). М., 2015. 9 с. [Polycystic ovary syndrome in women of reproductive age (modern diagnostic and management approaches. Clinical guidelines (protocol). M., 2015. 9 p. In Russian].


Дополнительные файлы

Для цитирования: Попова П.В., Горелова И.В., Гринева Е.В. Синдром поликистозных яичников и кардиоваскулярный риск. Артериальная гипертензия. 2018;24(6):654-665. https://doi.org/10.18705/1607-419X-2018-24-6-654-665

For citation: Popova P.V., Gorelova I.V., Grineva E.N. Polycystic ovary syndrome and cardiovascular risk. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2018;24(6):654-665. (In Russ.) https://doi.org/10.18705/1607-419X-2018-24-6-654-665

Просмотров: 33

Обратные ссылки

  • Обратные ссылки не определены.


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1607-419X (Print)
ISSN 2411-8524 (Online)