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Non traditional risk factors in women for coronary artery disease.

Consideration should also be given to non-traditional risk factors which, although not included in traditional validated risk score models, are known to confer an excess risk of cardiovascular events. These risks apply to select populations who are often under-represented in clinical trials and have therefore not been included in well-validated risk score models.

Risk factors in women

Risk factors in women can be sex-specific, usually related to sex-hormones, or conditions which are more prevalent in women conditions (Table).1 Reproductive and pregnancy-related history is recommended to elucidate relevant risk factors.2 Pregnancy-related conditions including gestational hypertension, preeclampsia and gestational diabetes are associated with a 2-fold increased risk of subsequent cardiovascular events including myocardial infarction and stroke. 3-5 Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE) disproportionately affect women and confer an increased risk of cardiovascular disease.6 A history of breast cancer and radiotherapy confers an increased risk which is proportional to the radiotherapy dose and field (left breast).7, 8


Female-specific cardiovascular risk factors

Female-predominant cardiovascular risk factors

Adverse pregnancy outcomes

Autoimmune inflammatory disease

Pregnancy related hypertension

Rheumatoid arthritis

Gestational hypertension

Systemic lupus erythematosus




Breast cancer

Gestational diabetes mellitus


Preterm delivery


Low birth weight for gestational age


Polycystic ovarian syndrome


Functional hypothalamic amenorrhoea


Reproductive hormones


Oral contraceptives


Hormone replacement


Modfied from Gulati, Circulation1

Chronic inflammatory diseases

Several chronic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection have been associated with an increased risk of cardiovascular disease which exceeds the expected risk conferred by comorbid traditional risk factors.6, 9-11 Rheumatoid arthritis is associated with an approximate 50% increase in the risk of myocardial infarction (MI) and stroke.12 SLE confers > 2 fold risk of cardiovascular events after adjusting for traditional risk factors.13 The risk is greatest in younger women aged 35-44 with SLE, who have a 50-fold increased rate of MI.14

Chronic kidney disease

Guideline recommendations have argued chronic kidney disease should be considered a coronary artery disease risk equivalent, similar to diabetes mellitus.15 Chronic kidney disease (CKD) is not only associated with high prevalence of traditional cardiovascular risk factors (e.g. hypertension, diabetes) but is also itself an independent and strong predictor of future cardiovascular events and mortality.16 Furthermore, patients with CKD are at greater risk of mortality related to cardiovascular disease rather than end stage kidney disease.17

Further References and Resources

1. Gulati M. Improving the Cardiovascular Health of Women in the Nation: Moving Beyond the Bikini Boundaries. Circulation. 2017;135:495-498.

2. Brown HL, Warner JJ, Gianos E, Gulati M, Hill AJ, Hollier LM, Rosen SE, Rosser ML, Wenger NK, American Heart A, the American College of O and Gynecologists. Promoting Risk Identification and Reduction of Cardiovascular Disease in Women Through Collaboration With Obstetricians and Gynecologists: A Presidential Advisory From the American Heart Association and the American College of Obstetricians and Gynecologists. Circulation. 2018.

3. Bellamy L, Casas JP, Hingorani AD and Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335:974.

4. Fadl H, Magnuson A, Ostlund I, Montgomery S, Hanson U and Schwarcz E. Gestational diabetes mellitus and later cardiovascular disease: a Swedish population based case-control study. BJOG. 2014;121:1530-6.

5. Kessous R, Shoham-Vardi I, Pariente G, Sherf M and Sheiner E. An association between gestational diabetes mellitus and long-term maternal cardiovascular morbidity. Heart. 2013;99:1118-21.

6. Mason JC and Libby P. Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premature cardiovascular events in rheumatologic conditions. Eur Heart J. 2015;36:482-9c.

7. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C and Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987-98.

8. Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ and Harris EE. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol. 2007;25:3031-7.

9. Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Cote R, Grover SA, Fortin PR, Clarke AE and Senecal JL. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001;44:2331-7.

10. Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, Butt AA, Bidwell Goetz M, Leaf D, Oursler KA, Rimland D, Rodriguez Barradas M, Brown S, Gibert C, McGinnis K, Crothers K, Sico J, Crane H, Warner A, Gottlieb S, Gottdiener J, Tracy RP, Budoff M, Watson C, Armah KA, Doebler D, Bryant K and Justice AC. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173:614-22.

11. Post WS, Budoff M, Kingsley L, Palella FJ, Jr., Witt MD, Li X, George RT, Brown TT and Jacobson LP. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014;160:458-67.

12. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ and Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71:1524-9.

13. Magder LS and Petri M. Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus. Am J Epidemiol. 2012;176:708-19.

14. Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA, Jr., Jansen-McWilliams L, D'Agostino RB and Kuller LH. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997;145:408-15.

15. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW, American Heart Association Councils on Kidney in Cardiovascular Disease HBPRCC, Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108:2154-69.

16. Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, Jafar T, Jassal SK, Landman GW, Muntner P, Roderick P, Sairenchi T, Schottker B, Shankar A, Shlipak M, Tonelli M, Townend J, van Zuilen A, Yamagishi K, Yamashita K, Gansevoort R, Sarnak M, Warnock DG, Woodward M, Arnlov J and Consortium CKDP. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3:514-25.

17. Thomas B, Matsushita K, Abate KH, Al-Aly Z, Arnlov J, Asayama K, Atkins R, Badawi A, Ballew SH, Banerjee A, Barregard L, Barrett-Connor E, Basu S, Bello AK, Bensenor I, Bergstrom J, Bikbov B, Blosser C, Brenner H, Carrero JJ, Chadban S, Cirillo M, Cortinovis M, Courville K, Dandona L, Dandona R, Estep K, Fernandes J, Fischer F, Fox C, Gansevoort RT, Gona PN, Gutierrez OM, Hamidi S, Hanson SW, Himmelfarb J, Jassal SK, Jee SH, Jha V, Jimenez-Corona A, Jonas JB, Kengne AP, Khader Y, Khang YH, Kim YJ, Klein B, Klein R, Kokubo Y, Kolte D, Lee K, Levey AS, Li Y, Lotufo P, El Razek HMA, Mendoza W, Metoki H, Mok Y, Muraki I, Muntner PM, Noda H, Ohkubo T, Ortiz A, Perico N, Polkinghorne K, Al-Radaddi R, Remuzzi G, Roth G, Rothenbacher D, Satoh M, Saum KU, Sawhney M, Schottker B, Shankar A, Shlipak M, Silva DAS, Toyoshima H, Ukwaja K, Umesawa M, Vollset SE, Warnock DG, Werdecker A, Yamagishi K, Yano Y, Yonemoto N, Zaki MES, Naghavi M, Forouzanfar MH, Murray CJL, Coresh J, Vos T, Global Burden of Disease GFRC, Consortium CKDP and Global Burden of Disease Genitourinary Expert G. Global Cardiovascular and Renal Outcomes of Reduced GFR. J Am Soc Nephrol. 2017;28:2167-2179.

Thanks to Dr Jennifer Yu Prince of Wales Hospital Sydney

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