Marfanoid appearance as a risk factor for atrial fibrillation in patients with osteoporosis

Objective: to investigate the relationship between some signs of hereditary connective tissue disorders (HCTDs) as a Marfanoid appearance (MA) and the risk of atrial fibrillation (AF) in female patients with osteoporosis (OP).

Subjects and methods. In 2014–2015, the investigation enrolled consecutively 104 women aged 58 to 70 years (mean age, 64.7±3.8 years) who had a verified diagnosis of primary OP and a body mass index of ≤25.0 kg/m2. The entries in the outpatient medical records and in the automated information system «Polyclinic» were retrospectively analyzed to divide the patients into 2 groups according to the sign of the documented diagnosis of AF. A study group consisted of 53 women (mean age, 65.6±5.2 years) with AF and OP; a control group included 38 patients (mean age, 64.9±4.7 years) with OP without AF; a control group comprised 38 patients (mean age, 65.1±3.9 years) without OP and AF. Anthropometric and phenotypical parameters and cardiovascular visceral signs were analyzed; the levels of transforming growth factor-β1 (TGFβ1) and interleukin (IL) 1β and 6 in the serum and those of deoxypyridinoline (DPD) in the urine were measured.

Results. Analysis of the phenotypical signs of HCTDs in the patients with OP has shown that those with OP and AF have external signs of dysmorphogenesis and meet the criteria of MA. Statistically significant correlations were found between the frequency of MA signs and the magnitude of all cardiac morphometric parameters and the visceral signs of HCTDs in the study group. The serum levels of IL-1β, IL-6, and TGFβ1 in these patients were significantly higher than in the comparison and control groups. There was also a high correlation between the signs of MA and the content of DPD in the study group.

Conclusion. The patients with OP and AF was found to have a statistically significant correlation of the phenotypical signs of dysmorphogenesis with the frequency of visceral signs of HCTD, the morphofunctional parameters of the heart, and the high concentration of cytokines and DPD. It may be suggested that there exists a genetically determined mechanism of connective tissue dysembryogenesis in OP, which is associated with the risk of AF.

1. Земцовский ЭВ, Малев ЭГ, Реева СВ. Системное вовлечение соединительной ткани и вовлечение соединительной ткани сердца как важная характеристика пролапса митрального клапана. Российский кардиологический журнал. 2014;9(113):54–60. [Zemtsovskii EV, Malev EG, Reeva SV. Systemic involvement of connective tissue and involving the connective tissue of the heart as an important characteristic of mitral valve prolapsed. Rossiiskii kardiologicheskii zhurnal. 2014;9(113):54-60. (In Russ.)].

2. Земцовский ЭВ. О понятиях «системное вовлечение соединительной ткани» и «вовлечение сердца» в свете пересмотра гентской нозологии для диагностики синдрома Марфана. Российский кардиологический журнал. 2013;1(99);3-7. [Zemtsovskii EV. Systemic connective tissue involvement and cardiac involvement: the 2010 revised Gent nosology in the Marfan syndrome diagnostics. Rossiiskii kardiologicheskii zhurnal. 2013;1(99):7-13. (In Russ.)].

3. Земцовский ЭВ. Сердечно-сосудистый континуум при синдроме Марфана. Сибирский медицинский журнал. 2011;3(2):13–8. [Zemtsovskii EV. Cardiovascular continuum in Marfan syndrome. Sibirskii meditsinskii zhurnal. 2011;3(2):13-8. (In Russ.)].

4. Земцовский ЭВ, Малев ЭГ, Лунева ЕБ. Наследственные нарушения соединительной ткани и внезапная сердечная смерть. Вестник аритмологии. 2010;(63):61-5. [Zemtsovskii EV, Malev EG, Luneva EB. Hereditary connective tissue disorders and sudden cardiac death. Vestnik aritmologii. 2010;(63):61-5. (In Russ.)].

5. Земцовский ЭВ, Малев ЭГ, Парфенова НН и др. Есть ли смысл выделять самостоятельный синдром дисплазии соединительной ткани сердца? Артериальная гипертензия. 2008;1(2): 18-23. [Zemtsovskii EV, Malev EG, Parfenova NN, et al. Does it make sense to allocate a separate syndrome of connective tissue dysplasia of heart? Arterial'naya gipertenziya. 2008;1(2):18-23. (In Russ.)].

6. Земцовский ЭВ, Парфенова НН, Малев ЭГ и др. Возрастные аспекты проблемы диагностики наследственных нарушений структуры и функции соединительной ткани. Артериальная гипертензия. 2008;2(2):63-8. [Zemtsovskii EV, Parfenova NN, Malev EG, et al. Age aspects of the problem of diagnostics of hereditary disorders of the structure and function of connective tissue. Arterial'naya gipertenziya. 2008; 2(2):63-8. (In Russ.)].

7. Российские рекомендации. Наследственные нарушения соединительной ткани. Всероссийское научное общество кардиологов. Российский кардиологический журнал. 2012;4(96)(Приложение 1). [Russian recommendations. Hereditary connective tissue disorders. Rossiiskii kardiologicheskii zhurnal. 2012;4(96)(Suppl. 1). (In Russ.)].

8. Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476-85.

9. Клеменов АВ. Недифференцированные дисплазии соединительной ткани. Москва: Информтех; 2005. 136 с. [Klemenov AV. Nedifferentsirovannye displazii soedinitel'noi tkani [Undifferentiated connective tissue dysplasia]. Moscow: Informtekh; 2005. 136 p.]

10. Земцовский ЭВ, Лобанов МЮ, Давтян КB. Диспластические синдромы и фенотипы как предикторы пароксизмов фибрилляции предсердий у пациентов со стабильным течением ишемической болезни сердца. Вестник аритмологии. 2009;(56):14-9. [Zemtsovskii EV, Lobanov MYu, Davtyan KV. Dysplastic syndromes and phenotypes as predictors of paroxysmal atrial fibrillation in patients with stable course of ischemic heart disease. Vestnik aritmologii. 2009;(56):14-9. (In Russ.)].

11. Торшин ИЮ, Громова ОА. Дисплазия соединительной ткани, магний и нуклеотидные полиморфизмы. Кардиология. 2008;(10):14-20. [Torshin IYu, Gromova OA. Connective tissue dysplasia, magnesium and nucleotide polymorphisms. Kardiologiya. 2008;(10):14-20. (In Russ.)].

12. Нечаева ГИ, Викторов ИА, Калинина ИЮ. Диагностика дисплазии соединительной ткани у лиц среднего и пожилого возраста в практике семейного врача. Российский семейный врач. 2004;8(2):47-54. [Nechaeva GI, Viktorov IA, Kalinina IYu. Diagnosis of connective tissue dysplasia in individuals of middle and old age in the practice of family doctor. Rossiiskii semeinyi vrach. 2004;8(2):47-54. (In Russ.)].

13. Kanis JA, McCloskey EV. Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013 Jan;24(1):23-57. doi: 10.1007/s00198-012- 2074-y. Epub 2012 Oct 19.

14. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int. 2005 Jun;16(6):581-9. Epub 2004 Dec 23.

15. Von der Recke P, Hansen MA, Hassager C. The association between low bone mass at the menopause and cardiovascular mortality. Am J Med. 1999 Mar;106(3):273-8.

16. Клеменов АВ. Номенклатура и алгоритм диагностики наследственных нарушений соединительной ткани. Клиницист. 2015;9(1):42-9. [Klemenov AV. Hereditary connective tissue disorders: nomenclature and diagnostic algoritm. Klinitsist. 2015;9(1):42-9. (In Russ.)].

17. Harradine KA. Mutations of TGF-β signaling molecules in human disease. Ann Med. 2006;38(6):403-14.

18. Blobe GC. Role of Transforming Growth Factor β in Human Disease. N Engl J Med. 2000 May 4;342(18):1350-8.

19. Itman C, Mendis S, Barakat B, et al. All in the family: TGF-beta family action in testis development. Reproduction. 2006 Aug;132(2):233-46.

20. Крылов МЮ, Маслова КА, Короткова ТА и др. Полиморфизм гена трансформирующего роста бета 1 при постменопаузальном остеопорозе. Научно-практическая ревматология. 2009;47(1):18-24. [Krylov MYu, Maslova KA, Korotkova TA, et al. Transforming growth factor β1 gene polymorphisms in postmenopausal osteoporosis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practiсе. 2009;47(1):18-24. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2009-137

21. Рудой АС. TGF β-зависимый патогенез синдрома марфана и родственных наследственных нарушений соединительной ткани. Артериальная гипертензия. 2009;15(2);23-6. [Rudoi AS. TGF-betadependent pathogenesis of marfan syndrome and related disorders. Arterial'naya gipertenziya. 2009; 15(2);23-6].