Skip to main content

Advertisement

Log in

Understanding the Role of Sex in Heart Valve and Major Vascular Diseases

  • Published:
Cardiovascular Engineering and Technology Aims and scope Submit manuscript

Abstract

Cardiovascular disease (CVD) is the major cause of mortality in the elderly population. The cost of CVD treatment and surgeries was over $300 billion in the United States alone in 2010, making this disorder a critical healthcare issue. Many studies have suggested sex as a risk factor for heart valve and major vascular diseases, such as aortic valve stenosis, mitral prolapse and regurgitation, atherosclerosis, coronary artery disease, and abdominal aortic aneurysm. Unfortunately, only a handful of studies have illustrated the role of sex in the etiology and progression of these disorders. Moreover, knowledge of biomolecular factors that affect these diseases in men and women is very limited. Numerous clinical studies have revealed obvious differences in the prevalence of these diseases between the sexes. These reports were supported by a few molecular and cellular physiology studies that associated this difference to sex and sex hormones. In particular, male sex has commonly been identified as a risk factor for majority of heart valve and vascular diseases, whereas females have been identified as higher risk for certain disorders as well. In addition, menopause is a critical issue that turns the tables against women and enhances complications in their cardiovascular structure due to hormonal change. In this review, major vascular and heart valve diseases for which sex is associated as a risk factor have been reviewed to highlight the importance of this risk factor in CVDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References

  1. Abedin, M., Y. Tintut, and L. L. Demer. Vascular calcification: mechanisms and clinical ramifications. Arterioscler. Thromb. Vasc. Biol. 24(7):1161–1170, 2004. doi:10.1161/01.ATV.0000133194.94939.42.

    Google Scholar 

  2. Aggarwal, S. R., M. A. Clavel, D. Messika-Zeitoun, C. Cueff, J. Malouf, P. A. Araoz, et al. Sex differences in aortic valve calcification measured by multidetector computed tomography in aortic stenosis. Circ. Cardiovasc. imaging 6(1):40–47, 2013. doi:10.1161/CIRCIMAGING.112.980052.

    Google Scholar 

  3. Ailawadi, G., J. L. Eliason, K. J. Roelofs, I. Sinha, K. K. Hannawa, E. P. Kaldjian, et al. Gender differences in experimental aortic aneurysm formation. Arterioscler. Thromb. Vasc. Biol. 24(11):2116–2122, 2004. doi:10.1161/01.ATV.0000143386.26399.84.

    Google Scholar 

  4. Al-Alao, B. S., H. Parissis, E. McGovern, M. Tolan, and V. K. Young. Gender influence in isolated coronary artery bypass graft surgery: a propensity match score analysis of early outcomes. Gen. Thorac. Cardiovasc. Surg. 60(7):417–424, 2012. doi:10.1007/s11748-012-0082-7.

    Google Scholar 

  5. Anand, D. V., E. Lim, D. Darko, P. Bassett, D. Hopkins, D. Lipkin, et al. Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/vascular calcification markers. J. Am. Coll. Cardiol. 50(23):2218–2225, 2007. doi:10.1016/j.jacc.2007.08.032.

    Google Scholar 

  6. Angelini, P. Coronary artery anomalies—current clinical issues: definitions, classification, incidence, clinical relevance, and treatment guidelines. Tex. Heart Inst. J. 29(4):271–278, 2002.

    Google Scholar 

  7. Angelini, P. Coronary artery anomalies: an entity in search of an identity. Circulation 115(10):1296–1305, 2007. doi:10.1161/CIRCULATIONAHA.106.618082.

    Google Scholar 

  8. Armstrong, V. W., P. Cremer, E. Eberle, A. Manke, F. Schulze, H. Wieland, et al. The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. Atherosclerosis. 62(3):249–257, 1986.

    Google Scholar 

  9. Aufderheide, S., D. Lax, and S. J. Goldberg. Gender differences in dehydration-induced mitral valve prolapse. Am. Heart J. 129(1):83–86, 1995.

    Google Scholar 

  10. Avierinos, J. F., J. Inamo, F. Grigioni, B. Gersh, C. Shub, and M. Enriquez-Sarano. Sex differences in morphology and outcomes of mitral valve prolapse. Ann. Intern. Med. 149(11):787–795, 2008.

    Google Scholar 

  11. Aydar, Y., H. U. Yazici, A. Birdane, M. Nasifov, A. Nadir, T. Ulus, et al. Gender differences in the types and frequency of coronary artery anomalies. Tohoku J. Exp. Med. 225(4):239–247, 2011.

    Google Scholar 

  12. Ballantyne, C. M., A. G. Olsson, T. J. Cook, M. F. Mercuri, T. R. Pedersen, and J. Kjekshus. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation 104(25):3046–3051, 2001.

    Google Scholar 

  13. Blake, H. A., W. C. Manion, T. W. Mattingly, and G. Baroldi. Coronary artery anomalies. Circulation 30:927–940, 1964.

    Google Scholar 

  14. Blankstein, R., R. P. Ward, M. Arnsdorf, B. Jones, Y. B. Lou, and M. Pine. Female gender is an independent predictor of operative mortality after coronary artery bypass graft surgery: contemporary analysis of 31 Midwestern hospitals. Circulation 112(9 Suppl):I323–I327, 2005. doi:10.1161/CIRCULATIONAHA.104.525139.

    Google Scholar 

  15. Carroll, J. D., E. P. Carroll, T. Feldman, D. M. Ward, R. M. Lang, D. McGaughey, et al. Sex-associated differences in left ventricular function in aortic stenosis of the elderly. Circulation 86(4):1099–1107, 1992.

    Google Scholar 

  16. Cavasin, M. A., Z. Tao, S. Menon, and X. P. Yang. Gender differences in cardiac function during early remodeling after acute myocardial infarction in mice. Life Sci. 75(18):2181–2192, 2004. doi:10.1016/j.lfs.2004.04.024.

    Google Scholar 

  17. Chakrabarti, S., O. Lekontseva, and S. T. Davidge. Estrogen is a modulator of vascular inflammation. IUBMB Life 60(6):376–382, 2008. doi:10.1002/iub.48.

    Google Scholar 

  18. Chen, J. H., and C. A. Simmons. Cell-matrix interactions in the pathobiology of calcific aortic valve disease: critical roles for matricellular, matricrine, and matrix mechanics cues. Circ. Res. 108(12):1510–1524, 2011. doi:10.1161/CIRCRESAHA.110.234237.

    Google Scholar 

  19. Chen, J. H., C. Y. Yip, E. D. Sone, and C. A. Simmons. Identification and characterization of aortic valve mesenchymal progenitor cells with robust osteogenic calcification potential. Am. J. Pathol. 174(3):1109–1119, 2009. doi:10.2353/ajpath.2009.080750.

    Google Scholar 

  20. Cho, B. S., K. J. Roelofs, J. W. Ford, P. K. Henke, and G. R. Upchurch, Jr. Decreased collagen and increased matrix metalloproteinase-13 in experimental abdominal aortic aneurysms in males compared with females. Surgery. 147(2):258–267, 2010. doi:10.1016/j.surg.2009.06.047.

    Google Scholar 

  21. Cutolo, M., S. Accardo, B. Villaggio, A. Barone, A. Sulli, D. A. Coviello, et al. Androgen and estrogen receptors are present in primary cultures of human synovial macrophages. J. Clin. Endocrinol. Metab. 81(2):820–827, 1996. doi:10.1210/jcem.81.2.8636310.

    Google Scholar 

  22. Darling, R. C., C. R. Messina, D. C. Brewster, and L. W. Ottinger. Autopsy study of unoperated abdominal aortic aneurysms. The case for early resection. Circulation 56(3 Suppl):II161–II164, 1977.

  23. Dechamethakun, S., S. Ikeda, T. Arai, N. Sato, M. Sawabe, and M. Muramatsu. Associations between the CDKN2A/B, ADTRP and PDGFD polymorphisms and the development of coronary atherosclerosis in Japanese patients. J. Atheroscler. Thromb. 2014.

  24. Devereux, R. B., W. T. Brown, R. Kramer-Fox, and I. Sachs. Inheritance of mitral valve prolapse: effect of age and sex on gene expression. Ann. Intern. Med. 97(6):826–832, 1982.

    Google Scholar 

  25. Devereux, R. B., I. Hawkins, R. Kramer-Fox, E. M. Lutas, I. W. Hammond, M. C. Spitzer, et al. Complications of mitral valve prolapse. Disproportionate occurrence in men and older patients. Am. J. Med. 81(5):751–758, 1986.

    Google Scholar 

  26. Eraso, L. H., E. Fukaya, E. R. Mohler, 3rd, D. Xie, D. Sha, and J. S. Berger. Peripheral arterial disease, prevalence and cumulative risk factor profile analysis. Eur. J. Prev. Cardiol. 2012. doi:10.1177/2047487312452968.

    Google Scholar 

  27. Frazier-Jessen, M. R., and E. J. Kovacs. Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages. J Immunol. 154(4):1838–1845, 1995.

    Google Scholar 

  28. Freed, L. A., D. Levy, R. A. Levine, M. G. Larson, J. C. Evans, D. L. Fuller, et al. Prevalence and clinical outcome of mitral-valve prolapse. N. Engl. J. Med. 341(1):1–7, 1999. doi:10.1056/NEJM199907013410101.

    Google Scholar 

  29. Freeman, R. V., and C. M. Otto. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation 111(24):3316–3326, 2005. doi:10.1161/CIRCULATIONAHA.104.486738.

    Google Scholar 

  30. Frontini, M. G., S. R. Srinivasan, A. Elkasabany, and G. S. Berenson. Distribution and cardiovascular risk correlates of serum triglycerides in young adults from a biracial community: the Bogalusa Heart Study. Atherosclerosis. 155(1):201–209, 2001.

    Google Scholar 

  31. Go, A. D. M., V. L. Roger, E. J. Benjamin, and J. D. Berry. Heazrt disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation 127, 2013.

  32. Go, A. S., D. Mozaffarian, V. L. Roger, E. J. Benjamin, J. D. Berry, M. J. Blaha, et al. Heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation 129(3):e28–e292, 2014. doi:10.1161/01.cir.0000441139.02102.80.

    Google Scholar 

  33. Grady, D., S. M. Rubin, D. B. Petitti, C. S. Fox, D. Black, B. Ettinger, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann. Intern. Med. 117(12):1016–1037, 1992.

    Google Scholar 

  34. Guo, X., M. Razandi, A. Pedram, G. Kassab, and E. R. Levin. Estrogen induces vascular wall dilation: mediation through kinase signaling to nitric oxide and estrogen receptors alpha and beta. J. Biol. Chem. 280(20):19704–19710, 2005. doi:10.1074/jbc.M501244200.

    Google Scholar 

  35. Gupta, V., J. E. Barzilla, J. S. Mendez, E. H. Stephens, E. L. Lee, C. D. Collard, et al. Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves. Cardiovasc. Pathol. 18(4):191–197, 2009. doi:10.1016/j.carpath.2008.05.001.

    Google Scholar 

  36. Hahn, C., and M. A. Schwartz. Mechanotransduction in vascular physiology and atherogenesis. Nat. Rev. Mol. Cell Biol. 10(1):53–62, 2009. doi:10.1038/nrm2596.

    Google Scholar 

  37. Hanke, H., S. Hanke, B. Bruck, U. Brehme, N. Gugel, G. Finking, et al. Inhibition of the protective effect of estrogen by progesterone in experimental atherosclerosis. Atherosclerosis 121(1):129–138, 1996.

    Google Scholar 

  38. Hannawa, K. K., J. L. Eliason, and G. R. Upchurch, Jr. Gender differences in abdominal aortic aneurysms. Vascular. 17(Suppl 1):S30–S39, 2009.

    Google Scholar 

  39. Hayward, C. S., R. P. Kelly, and P. Collins. The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc. Res. 46(1):28–49, 2000.

    Google Scholar 

  40. Heiss, G., A. R. Sharrett, R. Barnes, L. E. Chambless, M. Szklo, and C. Alzola. Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. Am. J. Epidemiol. 134(3):250–256, 1991.

    Google Scholar 

  41. Hickey, A. J., J. Wolfers, and D. E. Wilcken. Mitral-valve prolapse: prevalence in an Australian population. Med. J. Aust. 1(1):31–33, 1981.

    Google Scholar 

  42. Hogg, M. E., V. N. Varu, A. K. Vavra, D. A. Popowich, M. N. Banerjee, J. Martinez, et al. Effect of nitric oxide on neointimal hyperplasia based on sex and hormone status. Free Radic. Biol. Med. 50(9):1065–1074, 2011. doi:10.1016/j.freeradbiomed.2011.01.016.

    Google Scholar 

  43. Hogg, M. E., A. K. Vavra, M. N. Banerjee, J. Martinez, Q. Jiang, L. K. Keefer, et al. The role of estrogen receptor alpha and beta in regulating vascular smooth muscle cell proliferation is based on sex. J. Surg. Res. 173(1):e1–e10, 2012. doi:10.1016/j.jss.2011.09.021.

    Google Scholar 

  44. Iafrati, M. D., R. H. Karas, M. Aronovitz, S. Kim, T. R. Sullivan, Jr, D. B. Lubahn, et al. Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice. Nat. Med. 3(5):545–548, 1997.

    Google Scholar 

  45. Ikeda, T., T. Shirasawa, Y. Esaki, S. Yoshiki, and K. Hirokawa. Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta. J. Clin. Invest. 92(6):2814–2820, 1993. doi:10.1172/JCI116901.

    Google Scholar 

  46. Isenberg, B. C., C. Williams, and R. T. Tranquillo. Endothelialization and flow conditioning of fibrin-based media-equivalents. Ann. Biomed. Eng. 34(6):971–985, 2006. doi:10.1007/s10439-006-9101-0.

    Google Scholar 

  47. Isles, C. G., D. J. Hole, V. M. Hawthorne, and A. F. Lever. Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men. Lancet 339(8795):702–706, 1992.

    Google Scholar 

  48. Iung, B., G. Baron, E. G. Butchart, F. Delahaye, C. Gohlke-Barwolf, O. W. Levang, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur. Heart J. 24(13):1231–1243, 2003.

    Google Scholar 

  49. Jones, E. C., R. B. Devereux, M. J. Roman, J. E. Liu, D. Fishman, E. T. Lee, et al. Prevalence and correlates of mitral regurgitation in a population-based sample (The Strong Heart Study). Am. J. Cardiol. 87(3):298–304, 2001. doi:10.1016/S0002-9149(00)01362-X.

    Google Scholar 

  50. Kannel, W. B. The Framingham Study: historical insight on the impact of cardiovascular risk factors in men versus women. J. Gend. Specif. Med. 5(2):27–37, 2002.

    Google Scholar 

  51. Kannel, W. B., and P. W. Wilson. Risk factors that attenuate the female coronary disease advantage. Arch. Intern. Med. 155(1):57–61, 1995.

    Google Scholar 

  52. Kapoor, D., E. Goodwin, K. S. Channer, and T. H. Jones. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur. J. Endocrinol. 154(6):899–906, 2006. doi:10.1530/eje.1.02166.

    Google Scholar 

  53. Katz, D. J., J. C. Stanley, and G. B. Zelenock. Gender differences in abdominal aortic aneurysm prevalence, treatment, and outcome. J. Vasc. Surg. 25(3):561–568, 1997.

    Google Scholar 

  54. Kiely, D. K., P. A. Wolf, L. A. Cupples, A. S. Beiser, and W. B. Kannel. Physical activity and stroke risk: the Framingham Study. Am. J. Epidemiol. 140(7):608–620, 1994.

    Google Scholar 

  55. Kimura, M., K. Sudhir, M. Jones, E. Simpson, A. M. Jefferis, and J. P. Chin-Dusting. Impaired acetylcholine-induced release of nitric oxide in the aorta of male aromatase-knockout mice: regulation of nitric oxide production by endogenous sex hormones in males. Circ. Res. 93(12):1267–1271, 2003. doi:10.1161/01.RES.0000103172.98986.25.

    Google Scholar 

  56. Komesaroff, P. A., R. Murray, C. Rajkumar, M. D. Esler, G. L. Jennings, A. M. Dart, et al. Aromatase inhibition alters vascular reactivity and arterial compliance in men: a possible vascular role for endogenous sex hormones in males. Aust. N. Z. J. Med. 29(2):265–267, 1999.

    Google Scholar 

  57. Lapidus, L., and C. Bengtsson. Socioeconomic factors and physical activity in relation to cardiovascular disease and death. A 12 year follow up of participants in a population study of women in Gothenburg, Sweden. Br. Heart J. 55(3):295–301, 1986.

    Google Scholar 

  58. Laser, A., G. Lu, A. Ghosh, K. Roelofs, B. McEvoy, P. DiMusto, et al. Differential gender- and species-specific formation of aneurysms using a novel method of inducing abdominal aortic aneurysms. J. Surg. Res. 178(2):1038–1045, 2012. doi:10.1016/j.jss.2012.04.073.

    Google Scholar 

  59. Lax, D., M. Eicher, and S. J. Goldberg. Mild dehydration induces echocardiographic signs of mitral valve prolapse in healthy females with prior normal cardiac findings. Am. Heart J. 124(6):1533–1540, 1992.

    Google Scholar 

  60. Lederle, F. A., G. R. Johnson, S. E. Wilson, E. P. Chute, R. J. Hye, M. S. Makaroun, et al. The aneurysm detection and management study screening program: validation cohort and final results. Aneurysm Detection and Management Veterans Affairs Cooperative Study Investigators. Arch. Intern. Med. 160(10):1425–1430, 2000.

    Google Scholar 

  61. Lindner, V., S. K. Kim, R. H. Karas, G. G. Kuiper, J. A. Gustafsson, and M. E. Mendelsohn. Increased expression of estrogen receptor-beta mRNA in male blood vessels after vascular injury. Circ. Res. 83(2):224–229, 1998.

    Google Scholar 

  62. Lund, S. A., C. M. Giachelli, and M. Scatena. The role of osteopontin in inflammatory processes. J. Cell Commun. Signal. 3(3–4):311–322, 2009. doi:10.1007/s12079-009-0068-0.

    Google Scholar 

  63. Maas, A. H., and Y. E. Appelman. Gender differences in coronary heart disease. Neth Heart J. 18(12):598–603, 2010. doi:10.1007/s12471-010-0841-y.

    Google Scholar 

  64. Malorni, W., E. Straface, P. Matarrese, B. Ascione, R. Coinu, S. Canu, et al. Redox state and gender differences in vascular smooth muscle cells. FEBS Lett. 582(5):635–642, 2008. doi:10.1016/j.febslet.2008.01.034.

    Google Scholar 

  65. Manfredini, R., F. Fabbian, M. Pala, R. Tiseo, A. De Giorgi, F. Manfredini, et al. Seasonal and weekly patterns of occurrence of acute cardiovascular diseases: does a gender difference exist? J. Womens Health (Larchmt). 20(11):1663–1668, 2011. doi:10.1089/jwh.2011.2734.

    Google Scholar 

  66. Mannarino, E., and M. Pirro. Molecular biology of atherosclerosis. Clin. Cases Miner. Bone Metab. 5(1):57–62, 2008.

    Google Scholar 

  67. Manning, M. W., L. A. Cassi, J. Huang, S. J. Szilvassy, and A. Daugherty. Abdominal aortic aneurysms: fresh insights from a novel animal model of the disease. Vasc. Med. 7(1):45–54, 2002.

    Google Scholar 

  68. Maselli, A., P. Matarrese, E. Straface, S. Canu, F. Franconi, and W. Malorni. Cell sex: a new look at cell fate studies. FASEB J. 23(4):978–984, 2009. doi:10.1096/fj.08-114348.

    Google Scholar 

  69. Matsui, Y., S. R. Rittling, H. Okamoto, M. Inobe, N. Jia, T. Shimizu, et al. Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 23(6):1029–1034, 2003. doi:10.1161/01.ATV.0000074878.29805.D0.

    Google Scholar 

  70. McCoy, C. M., D. Q. Nicholas, and K. S. Masters. Sex-related differences in gene expression by porcine aortic valvular interstitial cells. PLoS ONE 7(7):e39980, 2012. doi:10.1371/journal.pone.0039980.

    Google Scholar 

  71. McNamara, J. R., H. Campos, J. M. Ordovas, J. Peterson, P. W. Wilson, and E. J. Schaefer. Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study. Arteriosclerosis 7(5):483–490, 1987.

    Google Scholar 

  72. Mendelsohn, M. E., and R. H. Karas. Molecular and cellular basis of cardiovascular gender differences. Science 308(5728):1583–1587, 2005. doi:10.1126/science.1112062.

    Google Scholar 

  73. Mendelson, K., and F. J. Schoen. Heart valve tissue engineering: concepts, approaches, progress, and challenges. Ann. Biomed. Eng. 34(12):1799–1819, 2006. doi:10.1007/s10439-006-9163-z.

    Google Scholar 

  74. Merkel, M., R. H. Eckel, and I. J. Goldberg. Lipoprotein lipase: genetics, lipid uptake, and regulation. J. Lipid Res. 43(12):1997–2006, 2002.

    Google Scholar 

  75. Mori, T., J. Durand, Y. Chen, J. A. Thompson, S. Bakir, and S. Oparil. Effects of short-term estrogen treatment on the neointimal response to balloon injury of rat carotid artery. Am. J. Cardiol. 85(10):1276–1279, 2000.

    Google Scholar 

  76. Nakamura, T., M. Ogita, J. Ako, and S. Momomura. Gender differences of plaque characteristics in elderly patients with stable angina pectoris: an intravascular ultrasonic radiofrequency data analysis. Int. J. Vasc. Med. 2010:134692, 2010. doi:10.1155/2010/134692.

    Google Scholar 

  77. Nathan, L., W. Shi, H. Dinh, T. K. Mukherjee, X. Wang, A. J. Lusis, et al. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc. Natl Acad. Sci. USA. 98(6):3589–3593, 2001. doi:10.1073/pnas.051003698.

    Google Scholar 

  78. Nkomo, V. T., J. M. Gardin, T. N. Skelton, J. S. Gottdiener, C. G. Scott, and M. Enriquez-Sarano. Burden of valvular heart diseases: a population-based study. Lancet 368(9540):1005–1011, 2006. doi:10.1016/S0140-6736(06)69208-8.

    Google Scholar 

  79. Nordmeyer, J., S. Eder, S. Mahmoodzadeh, P. Martus, J. Fielitz, J. Bass, et al. Upregulation of myocardial estrogen receptors in human aortic stenosis. Circulation 110(20):3270–3275, 2004. doi:10.1161/01.CIR.0000147610.41984.E8.

    Google Scholar 

  80. Osman, L., M. H. Yacoub, N. Latif, M. Amrani, and A. H. Chester. Role of human valve interstitial cells in valve calcification and their response to atorvastatin. Circulation 114(1 Suppl):I547–I552, 2006. doi:10.1161/CIRCULATIONAHA.105.001115.

    Google Scholar 

  81. Ott, M., V. Gogvadze, S. Orrenius, and B. Zhivotovsky. Mitochondria, oxidative stress and cell death. Apoptosis Int. J. Program. Cell Death 12(5):913–922, 2007. doi:10.1007/s10495-007-0756-2.

    Google Scholar 

  82. Owens, D. S., R. Katz, J. Takasu, R. Kronmal, M. J. Budoff, and K. D. O’Brien. Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA). Am. J. Cardiol. 105(5):701–708, 2010. doi:10.1016/j.amjcard.2009.10.071.

    Google Scholar 

  83. Pare, G., A. Krust, R. H. Karas, S. Dupont, M. Aronovitz, P. Chambon, et al. Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. Circ. Res. 90(10):1087–1092, 2002.

    Google Scholar 

  84. Redfield, M. M., S. J. Jacobsen, B. A. Borlaug, R. J. Rodeheffer, and D. A. Kass. Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation 112(15):2254–2262, 2005. doi:10.1161/CIRCULATIONAHA.105.541078.

    Google Scholar 

  85. Regitz-Zagrosek, V., and U. Seeland. Sex and gender differences in myocardial hypertrophy and heart failure. Wien. Med. Wochenschr. 161(5–6):109–116, 2011. doi:10.1007/s10354-011-0892-8.

    Google Scholar 

  86. Ritchie, J., J. N. Warnock, and A. P. Yoganathan. Structural characterization of the chordae tendineae in native porcine mitral valves. Ann. Thorac. Surg. 80(1):189–197, 2005. doi:10.1016/j.athoracsur.2005.02.011.

    Google Scholar 

  87. Sader, M. A., and D. S. Celermajer. Endothelial function, vascular reactivity and gender differences in the cardiovascular system. Cardiovasc. Res. 53(3):597–604, 2002.

    Google Scholar 

  88. Sakalihasan, N., R. Limet, and O. D. Defawe. Abdominal aortic aneurysm. Lancet 365(9470):1577–1589, 2005. doi:10.1016/S0140-6736(05)66459-8.

    Google Scholar 

  89. Sattur, S., S. Bates, and M. R. Movahed. Prevalence of mitral valve prolapse and associated valvular regurgitations in healthy teenagers undergoing screening echocardiography. Exp. Clin. Cardiol. 15(1):e13–e15, 2010.

    Google Scholar 

  90. Savage, D. D., R. J. Garrison, R. B. Devereux, W. P. Castelli, S. J. Anderson, D. Levy, et al. Mitral valve prolapse in the general population. 1. Epidemiologic features: the Framingham Study. Am. Heart J. 106(3):571–576, 1983.

    Google Scholar 

  91. Schoen, F. J. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation 118(18):1864–1880, 2008. doi:10.1161/CIRCULATIONAHA.108.805911.

    Google Scholar 

  92. Schreiner, P. J., G. Heiss, H. A. Tyroler, J. D. Morrisett, C. E. Davis, and R. Smith. Race and gender differences in the association of Lp(a) with carotid artery wall thickness—the atherosclerosis risk in communities (ARIC) study. Arterioscler. Thromb. Vasc. Biol. 16(3):471–478, 1996.

    Google Scholar 

  93. Sellaro, T. L., D. Hildebrand, Q. Lu, N. Vyavahare, M. Scott, and M. S. Sacks. Effects of collagen fiber orientation on the response of biologically derived soft tissue biomaterials to cyclic loading. J. Biomed. Mater. Res. A 80(1):194–205, 2007. doi:10.1002/jbm.a.30871.

    Google Scholar 

  94. Shah, P. M. Current concepts in mitral valve prolapse-diagnosis and management. J. Cardiol. 56(2):125–133, 2010. doi:10.1016/j.jjcc.2010.06.004.

    Google Scholar 

  95. Shaw, L. J., C. N. Bairey Merz, C. J. Pepine, S. E. Reis, V. Bittner, S. F. Kelsey, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J. Am. Coll. Cardiol. 47(3 Suppl):S4–S20, 2006. doi:10.1016/j.jacc.2005.01.072.

    Google Scholar 

  96. Singh, K., K. H. Bonaa, B. K. Jacobsen, L. Bjork, and S. Solberg. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study: the Tromso Study. Am. J. Epidemiol. 154(3):236–244, 2001.

    Google Scholar 

  97. Singh, R. G., R. Cappucci, R. Kramer-Fox, M. J. Roman, P. Kligfield, J. S. Borer, et al. Severe mitral regurgitation due to mitral valve prolapse: risk factors for development, progression, and need for mitral valve surgery. Am. J. Cardiol. 85(2):193–198, 2000. doi:10.1016/S0002-9149(99)00645-1.

    Google Scholar 

  98. Skavdahl, M., C. Steenbergen, J. Clark, P. Myers, T. Demianenko, L. Mao, et al. Estrogen receptor-beta mediates male-female differences in the development of pressure overload hypertrophy. Am. J. Physiol. Heart Circ. Physiol. 288(2):H469–H476, 2005. doi:10.1152/ajpheart.00723.2004.

    Google Scholar 

  99. Stensland-Bugge, E., K. H. Bonaa, and O. Joakimsen. Age and sex differences in the relationship between inherited and lifestyle risk factors and subclinical carotid atherosclerosis: the Tromso study. Atherosclerosis 154(2):437–448, 2001. doi:10.1016/S0021-9150(00)00486-X.

    Google Scholar 

  100. Storment, J. M., M. Meyer, and G. Osol. Estrogen augments the vasodilatory effects of vascular endothelial growth factor in the uterine circulation of the rat. Am. J. Obstet. Gynecol. 183(2):449–453, 2000. doi:10.1067/mob.2000.105910.

    Google Scholar 

  101. Straface, E., R. Vona, L. Gambardella, B. Ascione, M. Marino, P. Bulzomi, et al. Cell sex determines anoikis resistance in vascular smooth muscle cells. FEBS Lett. 583(21):3448–3454, 2009. doi:10.1016/j.febslet.2009.09.052.

    Google Scholar 

  102. Svartberg, J., D. von Muhlen, H. Schirmer, E. Barrett-Connor, J. Sundfjord, and R. Jorde. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study. Eur. J. Endocrinol. 150(1):65–71, 2004.

    Google Scholar 

  103. Tamura, T., S. Said, and A. M. Gerdes. Gender-related differences in myocyte remodeling in progression to heart failure. Hypertension 33(2):676–680, 1999.

    Google Scholar 

  104. Tan, Y. Y., G. C. Gast, and Y. T. van der Schouw. Gender differences in risk factors for coronary heart disease. Maturitas. 65(2):149–160, 2010. doi:10.1016/j.maturitas.2009.09.023.

    Google Scholar 

  105. Tangirala, R. K., E. M. Rubin, and W. Palinski. Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice. J. Lipid Res. 36(11):2320–2328, 1995.

    Google Scholar 

  106. Tanko, L. B., C. Christiansen, D. A. Cox, M. J. Geiger, M. A. McNabb, and S. R. Cummings. Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J. Bone Miner. Res. 20(11):1912–1920, 2005. doi:10.1359/JBMR.050711.

    Google Scholar 

  107. Tayal, D., B. Goswami, B. C. Koner, and V. Mallika. Role of homocysteine and lipoprotein (A) in atherosclerosis: an update. Biomed. Res. India 22(4):391–405, 2011.

    Google Scholar 

  108. Touyz, R. M., and E. L. Schiffrin. Reactive oxygen species in vascular biology: implications in hypertension. Histochem. Cell Biol. 122(4):339–352, 2004. doi:10.1007/s00418-004-0696-7.

    Google Scholar 

  109. Upchurch, Jr, G. R., and T. A. Schaub. Abdominal aortic aneurysm. Am. Fam. Phys. 73(7):1198–1204, 2006.

    Google Scholar 

  110. Vaccarino, V., J. L. Abramson, E. Veledar, and W. S. Weintraub. Sex differences in hospital mortality after coronary artery bypass surgery: evidence for a higher mortality in younger women. Circulation 105(10):1176–1181, 2002.

    Google Scholar 

  111. Villablanca, A., D. Lubahn, L. Shelby, K. Lloyd, and S. Barthold. Susceptibility to early atherosclerosis in male mice is mediated by estrogen receptor alpha. Arterioscler. Thromb. Vasc. Biol. 24(6):1055–1061, 2004. doi:10.1161/01.ATV.0000130467.65290.d4.

    Google Scholar 

  112. Villablanca, A. C., A. Tenwolde, M. Lee, M. Huck, S. Mumenthaler, and J. C. Rutledge. 17beta-estradiol prevents early-stage atherosclerosis in estrogen receptor-alpha deficient female mice. J. Cardiovasc. Transl. Res. 2(3):289–299, 2009. doi:10.1007/s12265-009-9103-z.

    Google Scholar 

  113. Virdis, A., L. Ghiadoni, S. Pinto, M. Lombardo, F. Petraglia, A. Gennazzani, et al. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation 101(19):2258–2263, 2000.

    Google Scholar 

  114. Vitale, C., M. E. Mendelsohn, and G. M. Rosano. Gender differences in the cardiovascular effect of sex hormones. Nat. Rev. Cardiol. 6(8):532–542, 2009. doi:10.1038/nrcardio.2009.105.

    Google Scholar 

  115. Wake, R., and M. Yoshiyama. Gender differences in ischemic heart disease. Recent Pat. Cardiovasc. Drug Discov. 4(3):234–240, 2009.

    Google Scholar 

  116. Wang, C., G. Jackson, T. H. Jones, A. M. Matsumoto, A. Nehra, M. A. Perelman, et al. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care 34(7):1669–1675, 2011. doi:10.2337/dc10-2339.

    Google Scholar 

  117. Watts, G. F. Treating patients with low high-density lipoprotein cholesterol: choices, issues and opportunities. Curr. Control Trials Cardiovasc. Med. 2(3):118–122, 2001.

    Google Scholar 

  118. Wilcken, D. E., and A. J. Hickey. Lifetime risk for patients with mitral valve prolapse of developing severe valve regurgitation requiring surgery. Circulation 78(1):10–14, 1988.

    Google Scholar 

  119. Williams, J. K., E. K. Honore, S. A. Washburn, and T. B. Clarkson. Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys. J. Am. Coll. Cardiol. 24(7):1757–1761, 1994.

    Google Scholar 

  120. Writing Group M, D. Lloyd-Jones, R. J. Adams, T. M. Brown, M. Carnethon, S. Dai, et al. Heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 121(7):e46–e215, 2010. doi:10.1161/CIRCULATIONAHA.109.192667.

  121. Yip, C. Y., J. H. Chen, R. Zhao, and C. A. Simmons. Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler. Thromb. Vasc. Biol. 29(6):936–942, 2009. doi:10.1161/ATVBAHA.108.182394.

    Google Scholar 

Download references

Conflict of interest

There is no conflict of interest to report for this review.

Statement of Human Studies

No human studies were conducted for this review.

Statement of Animal Studies

No animal studies were conducted for this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zannatul Ferdous.

Additional information

Associate Editor Sarah Wells oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Masjedi, S., Ferdous, Z. Understanding the Role of Sex in Heart Valve and Major Vascular Diseases. Cardiovasc Eng Tech 6, 209–219 (2015). https://doi.org/10.1007/s13239-015-0226-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13239-015-0226-x

Keywords

Navigation