Low density mammography is associated with increased carotid intima-media thickness in middle aged premenopausal women

Document Type : Original Article


1 Radiology Department, Kashan University of Medical Sciences, Kashan, Iran

2 Kashan University of Medical Sciences, Kashan, Iran

3 Faculty of Health, Kashan University of Medical Sciences, Kashan, Iran

4 Surgery Department, Kashan University of Medical Sciences, Kashan, Iran


Objectives: As the hormonal status of women does influence both mammographic breast density and atherosclerosis, the aim of the study was to evaluate the association between breast density on mammography and carotid intima-media thickness (CIMT).
Methods: Two-hundred premenopausal women with mammographic breast density of one (n=100) or four (n=100) were selected for this cross-sectional study. CIMT was measured according to the guidelines of Mannheim Consensus. The correlation between mammographic breast density and CIMT was assessed.
Results: Mean age was 45.9±3.4 years and 45.8±3.2 years in the groups with mammographic density of 1 and 4, respectively, which showed no significant difference. CIMT correlated with age with a Pearson Correlation Coefficient of 0.470 (p<0.001). CIMT was significantly higher in women with ACR-mammographic density of 1 (p<0.001).
Conclusion: Women with mammographic breast density of 1 revealed a higher CIMT. Further studies evaluating breast density and CIMT in pre- and postmenopausal women and assessing simultaneously the serum hormone level could give more information about the cause and effect of this correlation.


Nushin Moussavi [Pubmed] [Google Scholar]


  1. Ronzani FAT, Kirchmaier FM, Monteze NM, Magacho EJC, Bastos MG, Fernandes N. Routine mammography: an opportunity for the diagnosis of chronic degenerative diseases? A cross-sectional study. Radiologia brasileira. 2017;50(2):82-9. doi:10.1590/0100-3984.2015.0173 PMid:28428650 PMCid:PMC5396997
  2. Margolies L, Salvatore M, Hecht HS, Kotkin S, Yip R, Baber U, et al. Digital Mammography and Screening for Coronary Artery Disease. JACC Cardiovasc Imaging. 2016;9(4):350-60. doi:10.1016/j.jcmg.2015.10.022 PMid:27053465
  3. Sedighi N, Radmard AR, Radmehr A, Hashemi P, Hajizadeh A, Taheri AP. Breast arterial calcification and risk of carotid atherosclerosis: focusing on the preferentially affected layer of the vessel wall. Eur J Radiol. 2011;79(2):250-6.
    doi:10.1016/j.ejrad.2010.04.007 PMid:20478674
  4. Trimboli RM, Codari M, Guazzi M, Sardanelli F. Screening mammography beyond breast cancer: breast arterial calcifications as a sex-specific biomarker of cardiovascular risk. European journal of radiology. 2019;119:108636. doi:10.1016/j.ejrad.2019.08.005 PMid:31493727
  5. Lee SC PM, Bellinge J, Stone J, Wylie E, Schultz C. Is breast arterial calcification associated with coronary artery disease?-A systematic review and meta-analysis. PloS one. 2020;15(7):e0236598.
    doi:10.1371/journal.pone.0236598 PMid:32722699 PMCid:PMC7386618
  6. Grassmann F, Yang H, Eriksson M, Azam S, Hall P, Czene K. Mammographic features are associated with cardiometabolic disease risk and mortality. Eur Heart J. 2021; 42(34): 3361-70. doi:10.1093/eurheartj/ehab502 PMid:34338750 PMCid:PMC8423470
  7. Checka CM, Chun JE, Schnabel FR, Lee J, Toth H. The relationship of mammographic density and age: implications for breast cancer screening. AJR Am J Roentgenol. 2012;198(3):W292-5. doi:10.2214/AJR.10.6049 PMid:22358028
  8. Gabrielson M, Azam S, Hardell E, Holm M, Ubhayasekera KA, Eriksson M, et al. Hormonal determinants of mammographic density and density change. Breast Cancer Res : BCR. 2020; 22 (1): 95. doi:10.1186/s13058-020-01332-4 PMid:32847607 PMCid:PMC7449090
  9. Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid Intima-Media Thickness for Atherosclerosis. J Atheroscler Thromb 2016; 23 (1): 18-31. doi:10.5551/jat.31989 PMid:26460381
  10. Sickles E, D'Orsi CJ, Bassett LW. ACR BI-RADS® Mammography. 2013. In: ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System [Internet]. Reston, VA, American College of Radiology.
  11. Greendale GA, Palla SL, Ursin G, Laughlin GA, Crandall C, Pike MC, et al. The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Am J Epidemiol. 2005;162(9):826-34. doi:10.1093/aje/kwi286 PMid:16177147
  12. Touboul P, Hennerici M, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim Carotid Intima-Media Thickness and Plaque Consensus (2004-2006-2011): An Update on Behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovascular diseases (Basel, Switzerland). 2012;34(4):290-6. doi:10.1159/000343145 PMid:23128470 PMCid:PMC3760791
  13. Touboul PJ. Intima-media thickness of carotid arteries. Front Neurol Neurosci 2015;36:31-9. doi:10.1159/000366234 PMid:25531661
  14. Mauro Secco J, Elias S, Valletta de Carvalho C, Dale Cotrim Guerreiro da Silva I, Jung de Campos K, Facina G, et al. Mammographic density among indigenous women in forested areas in the state of Amapa, Brazil: a cross-sectional study. Sao Paulo Med J = Revista paulista de medicina. 2017; 135 (4):355-62. doi:10.1590/1516-3180.2016.0146150317 PMid:28767986 PMCid:PMC10016001
  15. Lee E, Ingles SA, Van Den Berg D, Wang W, Lavallee C, Huang MH, et al. Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Menopause (New York, NY). 2012;19(3):302-10. doi:10.1097/gme.0b013e3182310f9f PMid:22105149 PMCid:PMC4497814
  16. Johansson H, Gandini S, Bonanni B, Mariette F, Guerrieri-Gonzaga A, Serrano D, et al. Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women. Breast Cancer Res Treat. 2008;108(1):57-67. doi:10.1007/s10549-007-9577-9 PMid:17468953
  17. Kische H, Gross S, Wallaschofski H, Volzke H, Dorr M, Nauck M, et al. Serum androgen concentrations and subclinical measures of cardiovascular disease in men and women. Atherosclerosis. 2016; 247:193-200. doi:10.1016/j.atherosclerosis.2016.02.020 PMid:26926599
  18. Celestino Catao Da Silva D, Nogueira De Almeida Vasconcelos A, Cleto Maria Cerqueira J, De Oliveira Cipriano Torres D, Oliveira Dos Santos AC, De Lima Ferreira Fernandes Costa H, et al. Endogenous sex hormones are not associated with subclinical atherosclerosis in menopausal women. Minerva Ginecologica. 2013;65(3):297-302.
  19. El Khoudary SR, Wildman RP, Matthews K, Thurston RC, Bromberger JT, Sutton-Tyrrell K. Endogenous sex hormones impact the progression of subclinical atherosclerosis in women during the menopausal transition. Atherosclerosis. 2012;225(1): 180-6. doi:10.1016/j.atherosclerosis.2012.07.025 PMid:22981430 PMCid:PMC3478422
  20. Calderon-Margalit R, Schwartz SM, Wellons MF, Lewis CE, Daviglus ML, Schreiner PJ, et al. Prospective association of serum androgens and sex hormone-binding globulin with subclinical cardiovascular disease in young adult women: the "Coronary Artery Risk Development in Young Adults" women's study. The J Clin Endocrinol Metab. 2010;95(9): 4424-31. doi:10.1210/jc.2009-2643 PMid:20554712 PMCid:PMC2936074
  21. Manson JE, Aragaki AK, Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA. 2017;318(10):927-38.
    doi:10.1001/jama.2017.11217 PMid:28898378 PMCid:PMC5728370
  22. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, et al. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016; 374(13):1221-31. doi:10.1056/NEJMoa1505241 PMid:27028912 PMCid:PMC4921205
  23. Keaney JF, Jr., Solomon CG. Postmenopausal Hormone Therapy and Atherosclerosis- Time Is of the Essence. N Engl J Med. 2016;374(13):1279-80. doi:10.1056/NEJMe1602846 PMid:27028919
  24. Hodis HN, Mack WJ, Shoupe D, Azen SP, Stanczyk FZ, Hwang-Levine J, et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause (New York, NY). 2015;22(4):391-401. doi:10.1097/GME.0000000000000343 PMid:25380275 PMCid:PMC4376597
  25. Palmisano BT, Zhu L, Stafford JM. Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017; 1043: 227-56. doi:10.1007/978-3-319-70178-3_12 PMid:29224098 PMCid:PMC5763482
  26. Kotani K, Sahebkar A, Serban C, Andrica F, Toth PP, Jones SR, et al. Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients. Atherosclerosis. 2015;242(1):87-96. doi:10.1016/j.atherosclerosis.2015.06.056 PMid:26186655
  27. Sahebkar A, Serban MC, Penson P, Gurban C, Ursoniu S, Toth PP, et al. The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis. Drugs. 2017;77(11):1187-97. doi:10.1007/s40265-017-0767-4 PMid:28573436 PMCid:PMC5501893
  28. Hendriks EJ, de Jong PA, van der Graaf Y, Mali WP, van der Schouw YT, Beulens JW. Breast arterial calcifications: a systematic review and meta-analysis of their determinants and their association with cardiovascular events. Atherosclerosis. 2015;239 (1):11-20. doi:10.1016/j.atherosclerosis.2014.12.035 PMid:25568948