Korean Circ J.  2023 Oct;53(10):655-676. 10.4070/kcj.2023.0205.

Sex Differences in Coronary Artery Disease: Insights From the KoRean wOmen’S chest pain rEgistry (KoROSE)

• Kim HL
• Kim MA

• KMID: 2546990
• DOI: http://doi.org/10.4070/kcj.2023.0205

Abstract

Interest in sex differences in coronary artery disease (CAD) has been steadily increasing. Concurrently, most of the data on these differences have primarily been Western-oriented. The KoRean wOmen’S chest pain rEgistry (KoROSE), started in 2011, has since published numerous research findings. This review aims to summarize the reported differences between men and women in CAD, integrating data from KoROSE. Cardiovascular risk in postmenopausal women escalates dramatically due to the decrease in estrogen levels, which normally offer cardiovascular protective effects. Lower estrogen levels can lead to abdominal obesity, insulin resistance, increased blood pressure, and endothelial dysfunction in older women. Upon analyzing patients with CAD, women are typically older and exhibit more cardiovascular risk factors than men. Diagnosing CAD in women tends to be delayed due to their symptoms being more atypical than men’s. While in-hospital outcome was similar between sexes, bleeding complications after percutaneous coronary intervention occur more frequently in women. The differences in long-term prognosis for CAD patients between men and women are still a subject of ongoing debate. Pregnancy and reproductive factors also play a significant role as risk factors for cardiovascular disease in women. A notable sex disparity exists, with women found to use fewer cardiovascular protective drugs and undergo fewer interventional or surgical procedures than men. Additionally, women participate less frequently than men in clinical research. Through concerted efforts to increase awareness of sex differences and mitigate sex disparity, personalized treatment can be provided. This approach can ultimately improve patient prognosis.

Keyword

Coronary artery disease; Sex differences; Women’s health

Figure

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  Figure 1 CAD risk factors in Korean women.CAD = coronary artery disease; LV = left ventricular.

• 

  Figure 2 Sex disparity in CAD and solutions for overcoming it.CABG = coronary artery bypass grafting; CAD = coronary artery disease; PCI = percutaneous coronary intervention.

Reference

1. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2023 update: a report from the American Heart Association. Circulation. 2023; 147:e93–621. PMID: 36695182.

2. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011; 364:829–841. PMID: 21366474.

3. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360:1903–1913. PMID: 12493255.

4. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009; 373:1083–1096. PMID: 19299006.

5. Prospective Studies Collaboration. Lewington S, Whitlock G, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007; 370:1829–1839. PMID: 18061058.

6. Jha P, Ramasundarahettige C, Landsman V, et al. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013; 368:341–350. PMID: 23343063.

7. Arafa A, Lee HH, Eshak ES, et al. Modifiable risk factors for cardiovascular disease in Korea and Japan. Korean Circ J. 2021; 51:643–655. PMID: 34227266.

8. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019; 74:1376–1414. PMID: 30894319.

9. Visseren FL, Mach F, Smulders YM, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021; 42:3227–3337. PMID: 34458905.

10. Kim HL, Chung J, Kim KJ, et al. Lifestyle modification in the management of metabolic syndrome: statement from Korean Society of CardioMetabolic Syndrome (KSCMS). Korean Circ J. 2022; 52:93–109. PMID: 35128848.

11. Baek J, Lee H, Lee HH, Heo JE, Cho SM, Kim HC. Thirty-six year trends in mortality from diseases of circulatory system in Korea. Korean Circ J. 2021; 51:320–332. PMID: 33821581.

12. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003; 290:898–904. PMID: 12928466.

13. Lee HH, Cho SM, Lee H, et al. Korea heart disease fact sheet 2020: analysis of nationwide data. Korean Circ J. 2021; 51:495–503. PMID: 34085422.

14. Agarwala A, Goldberg A. Special considerations for lipid-lowering therapy in women reflecting recent randomized trials. Curr Atheroscler Rep. 2021; 23:42. PMID: 34146167.

15. Mosca L, Hammond G, Mochari-Greenberger H, et al. Fifteen-year trends in awareness of heart disease in women: results of a 2012 American Heart Association national survey. Circulation. 2013; 127:1254–1263. e1–1229. PMID: 23429926.

16. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018; 137:e67–492. PMID: 29386200.

17. Women’s Heart Disease Research Working Group (KR). Women’s Heart Disease Research Working Group’s homepage [Internet]. Incheon: Women’s Heart Disease Research Working Group;2023. cited 2023 July 18. Available from: https://www.womensheart.or.kr/.

18. Vogel B, Acevedo M, Appelman Y, et al. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet. 2021; 397:2385–2438. PMID: 34010613.

19. Statistics Korea. Causes of death statistics [Internet]. Daejeon: Statistics Korea;c2023. cited 2023 July 18. Available from: https://kostat.go.kr/ansk/.

20. North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. 2012; 110:1097–1108. PMID: 22499900.

21. Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009; 25:563–577. PMID: 19944261.

22. Centers for Disease Control and Prevention. National Center for Health Statistics. Summary health statistics: National Health Interview Survey, 2018: table A-1 [Internet]. Atlanta (GA): Centers for Disease Control and Prevention;2018. cited 2022 March 22. Available from: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2018_SHS_Table_A-1.pdf.

23. Kim HL, Kim HJ, Kim M, et al. Sex differences in coronary angiographic findings in patients with stable chest pain: analysis of data from the KoRean wOmen’S chest pain rEgistry (KoROSE). Biol Sex Differ. 2022; 13:2. PMID: 34980251.

24. Kim HL, Jang JS, Kim MA, et al. Gender differences of in-hospital outcomes in patients undergoing percutaneous coronary intervention in the drug-eluting stent era. Medicine (Baltimore). 2019; 98:e15557. PMID: 31096458.

25. Korea Acute Myocardial Infarction Registry (KAMIR) Investigators. Lee KH, Jeong MH, et al. Gender differences of success rate of percutaneous coronary intervention and short term cardiac events in Korea Acute Myocardial Infarction Registry. Int J Cardiol. 2008; 130:227–234. PMID: 18077018.

26. Kunadian V, Qiu W, Lagerqvist B, et al. Gender differences in outcomes and predictors of all-cause mortality after percutaneous coronary intervention (data from United Kingdom and Sweden). Am J Cardiol. 2017; 119:210–216. PMID: 27816119.

27. Jacobs AK, Johnston JM, Haviland A, et al. Improved outcomes for women undergoing contemporary percutaneous coronary intervention: a report from the National Heart, Lung, and Blood Institute Dynamic registry. J Am Coll Cardiol. 2002; 39:1608–1614. PMID: 12020487.

28. Iyanoye A, Moreyra AE, Swerdel JN, et al. Gender disparity in the use of drug-eluting stents during percutaneous coronary intervention for acute myocardial infarction. Catheter Cardiovasc Interv. 2015; 86:221–228. PMID: 25645156.

29. Kim HC, Lee H, Lee HH, et al. Korea hypertension fact sheet 2021: analysis of nationwide population-based data with special focus on hypertension in women. Clin Hypertens. 2022; 28:1. PMID: 34980274.

30. Brahmbhatt Y, Gupta M, Hamrahian S. Hypertension in premenopausal and postmenopausal women. Curr Hypertens Rep. 2019; 21:74. PMID: 31451980.

31. Seo E, Jung S, Lee H, Kim HC. Sex-specific trends in the prevalence of hypertension and the number of people with hypertension: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES) 1998-2018. Korean Circ J. 2022; 52:382–392. PMID: 35257521.

32. Shaw LJ, Bugiardini R, Merz CN. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol. 2009; 54:1561–1575. PMID: 19833255.

33. Park J, Kim HL, Kim MA, et al. Traditional cardiovascular risk factors and obstructive coronary disease in patients with stable chest pain: gender-specific analysis. Cardiometab Syndr J. 2021; 1:101–110.

34. Juutilainen A, Kortelainen S, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Diabetes Care. 2004; 27:2898–2904. PMID: 15562204.

35. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006; 332:73–78. PMID: 16371403.

36. Prospective Studies Collaboration and Asia Pacific Cohort Studies Collaboration. Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies. Lancet Diabetes Endocrinol. 2018; 6:538–546. PMID: 29752194.

37. Lu Y, Zhou S, Dreyer RP, et al. Sex differences in lipid profiles and treatment utilization among young adults with acute myocardial infarction: results from the VIRGO study. Am Heart J. 2017; 183:74–84. PMID: 27979045.

38. Rhee EJ. Prevalence and current management of cardiovascular risk factors in Korean adults based on fact sheets. Endocrinol Metab. 2020; 35:85–94.

39. Peters SA, Muntner P, Woodward M. Sex differences in the prevalence of, and trends in, cardiovascular risk factors, treatment, and control in the United States, 2001 to 2016. Circulation. 2019; 139:1025–1035. PMID: 30779652.

40. Abbey M, Owen A, Suzakawa M, Roach P, Nestel PJ. Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity. Maturitas. 1999; 33:259–269. PMID: 10656504.

41. Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med. 1971; 74:1–12. PMID: 5539274.

42. Grundtvig M, Hagen TP, German M, Reikvam A. Sex-based differences in premature first myocardial infarction caused by smoking: twice as many years lost by women as by men. Eur J Cardiovasc Prev Rehabil. 2009; 16:174–179. PMID: 19247184.

43. Huxley RR, Woodward M. Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies. Lancet. 2011; 378:1297–1305. PMID: 21839503.

44. Peters SA, Huxley RR, Woodward M. Smoking as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke. 2013; 44:2821–2828. PMID: 23970792.

45. Prescott E, Hippe M, Schnohr P, Hein HO, Vestbo J. Smoking and risk of myocardial infarction in women and men: longitudinal population study. BMJ. 1998; 316:1043–1047. PMID: 9552903.

46. Kim YH, Her AY, Jeong MH, et al. Sex difference after acute myocardial infarction patients with a history of current smoking and long-term clinical outcomes: results of KAMIR registry. Cardiol J. 2022; 29:954–965. PMID: 33438183.

47. Pirie K, Peto R, Reeves GK, Green J, Beral V. Million Women Study Collaborators. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet. 2013; 381:133–141. PMID: 23107252.

48. Woodward M, Lam TH, Barzi F, et al. Smoking, quitting, and the risk of cardiovascular disease among women and men in the Asia-Pacific region. Int J Epidemiol. 2005; 34:1036–1045. PMID: 15914503.

49. Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384:766–781. PMID: 24880830.

50. Krotkiewski M, Björntorp P, Sjöström L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983; 72:1150–1162. PMID: 6350364.

51. Zhang C, Rexrode KM, van Dam RM, Li TY, Hu FB. Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women. Circulation. 2008; 117:1658–1667. PMID: 18362231.

52. Cho JH, Kim HL, Kim MA, et al. Association between obesity type and obstructive coronary artery disease in stable symptomatic postmenopausal women: data from the KoRean wOmen’S chest pain rEgistry (KoROSE). Menopause. 2019; 26:1272–1276. PMID: 31688574.

53. Jee SH, Sull JW, Park J, et al. Body-mass index and mortality in Korean men and women. N Engl J Med. 2006; 355:779–787. PMID: 16926276.

54. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005; 352:1685–1695. PMID: 15843671.

55. Chung J, Min KW, Son BK, Kim DH, Kim HL. Association between histological severity of Helicobacter pylori infection and cardiovascular risk scores in the Korean population. Atherosclerosis. 2021; 333:124–130. PMID: 34429194.

56. Mason JC, Libby P. Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premature cardiovascular events in rheumatologic conditions. Eur Heart J. 2015; 36:482–489c. PMID: 25433021.

57. Di Florio DN, Sin J, Coronado MJ, Atwal PS, Fairweather D. Sex differences in inflammation, redox biology, mitochondria and autoimmunity. Redox Biol. 2020; 31:101482. PMID: 32197947.

58. Kim HL, Kim MA, Oh S, et al. Sex differences in traditional and nontraditional risk factors for obstructive coronary artery disease in stable symptomatic patients. J Womens Health (Larchmt). 2019; 28:212–219. PMID: 29958048.

59. Wang TJ, Larson MG, Levy D, et al. C-reactive protein is associated with subclinical epicardial coronary calcification in men and women: the Framingham Heart Study. Circulation. 2002; 106:1189–1191. PMID: 12208790.

60. Khera A, de Lemos JA, Peshock RM, et al. Relationship between C-reactive protein and subclinical atherosclerosis: the Dallas Heart Study. Circulation. 2006; 113:38–43. PMID: 16380546.

61. Yamashita T, Sasaki N, Kasahara K, Hirata K. Anti-inflammatory and immune-modulatory therapies for preventing atherosclerotic cardiovascular disease. J Cardiol. 2015; 66:1–8. PMID: 25744783.

62. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003; 289:194–202. PMID: 12517230.

63. Liu S, Moussa M, Wassef AW, Hiebert BM, Hussain F, Jassal DS. The utility of systolic and diastolic echocardiographic parameters for predicting coronary artery disease burden as defined by the SYNTAX score. Echocardiography. 2016; 33:14–22. PMID: 26114805.

64. Lin FY, Zemedkun M, Dunning A, et al. Extent and severity of coronary artery disease by coronary CT angiography is associated with elevated left ventricular diastolic pressures and worsening diastolic function. J Cardiovasc Comput Tomogr. 2013; 7:289–96.e1. PMID: 24268115.

65. Ohara T, Little WC. Evolving focus on diastolic dysfunction in patients with coronary artery disease. Curr Opin Cardiol. 2010; 25:613–621. PMID: 20827179.

66. Fischer M, Baessler A, Hense HW, et al. Prevalence of left ventricular diastolic dysfunction in the community. Results from a Doppler echocardiographic-based survey of a population sample. Eur Heart J. 2003; 24:320–328. PMID: 12581679.

67. Kim HM, Kim HL, Kim MA, et al. Additional roles of diastolic parameters in the diagnosis of obstructive coronary artery disease. Coron Artery Dis. 2021; 32:145–151. PMID: 33060532.

68. Kim HL, Kim MA, Oh S, et al. Sex difference in the association between metabolic syndrome and left ventricular diastolic dysfunction. Metab Syndr Relat Disord. 2016; 14:507–512. PMID: 27710153.

69. Kim HL, Lim WH, Seo JB, et al. Association between arterial stiffness and left ventricular diastolic function in relation to gender and age. Medicine (Baltimore). 2017; 96:e5783. PMID: 28072727.

70. Kim M, Kim HL, Lim WH, et al. Association between arterial stiffness and left ventricular diastolic function: a large population-based cross-sectional study. Front Cardiovasc Med. 2022; 9:1001248. PMID: 36312236.

71. Kim KJ, Kim HL, Kim MJ, et al. Gender difference in the association between aortic pulse pressure and left ventricular filling pressure in the elderly: an invasive hemodynamic study. J Card Fail. 2017; 23:224–230. PMID: 28087427.

72. Cho DH, Kim MA, Choi J, et al. Sex differences in the relationship between left ventricular diastolic dysfunction and coronary artery disease: from the Korean Women’s Chest Pain Registry. J Womens Health (Larchmt). 2018; 27:912–919. PMID: 29634453.

73. Schulz R, Beach SR, Ives DG, Martire LM, Ariyo AA, Kop WJ. Association between depression and mortality in older adults: the Cardiovascular Health Study. Arch Intern Med. 2000; 160:1761–1768. PMID: 10871968.

74. Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012; 9:360–370. PMID: 22473079.

75. Wei J, Rooks C, Ramadan R, et al. Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease. Am J Cardiol. 2014; 114:187–192. PMID: 24856319.

76. Aboa-Eboulé C, Brisson C, Maunsell E, et al. Job strain and risk of acute recurrent coronary heart disease events. JAMA. 2007; 298:1652–1660. PMID: 17925517.

77. Vaccarino V, Sullivan S, Hammadah M, et al. Mental stress-induced-myocardial ischemia in young patients with recent myocardial infarction: sex differences and mechanisms. Circulation. 2018; 137:794–805. PMID: 29459465.

78. Samad Z, Boyle S, Ersboll M, et al. Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: insights from the REMIT study. J Am Coll Cardiol. 2014; 64:1669–1678. PMID: 25323254.

79. Kim NH, Lee YH, Kim M. Community-dwelling individuals with coronary artery disease have higher risk of depression than the general population in female, but not in male. Korean Circ J. 2021; 51:752–763. PMID: 34227268.

80. Cho KI, Shim WJ, Park SM, et al. Association of depression with coronary artery disease and QTc interval prolongation in women with chest pain: data from the KoRean wOmen’S chest pain rEgistry (KoROSE) study. Physiol Behav. 2015; 143:45–50. PMID: 25727022.

81. Almuwaqqat Z, Sullivan S, Hammadah M, et al. Sex-specific association between coronary artery disease severity and myocardial ischemia induced by mental stress. Psychosom Med. 2019; 81:57–66. PMID: 30571661.

82. O’Kelly AC, Michos ED, Shufelt CL, et al. Pregnancy and reproductive risk factors for cardiovascular disease in women. Circ Res. 2022; 130:652–672. PMID: 35175837.

83. Canoy D, Beral V, Balkwill A, et al. Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort. Circulation. 2015; 131:237–244. PMID: 25512444.

84. Lee JJ, Cook-Wiens G, Johnson BD, et al. Age at menarche and risk of cardiovascular disease outcomes: findings from the National Heart Lung and Blood Institute-sponsored women’s ischemia syndrome evaluation. J Am Heart Assoc. 2019; 8:e012406. PMID: 31165670.

85. Kim HL, Kim MA, Shim WJ, et al. Reproductive factors predicting angiographic obstructive coronary artery disease: the KoRean wOmen’S chest pain rEgistry (KoROSE). J Womens Health (Larchmt). 2016; 25:443–448. PMID: 26653708.

86. 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; 17:37. PMID: 29519249.

87. Haug EB, Horn J, Markovitz AR, et al. Association of conventional cardiovascular risk factors with cardiovascular disease after hypertensive disorders of pregnancy: analysis of the Nord-Trøndelag Health Study. JAMA Cardiol. 2019; 4:628–635. PMID: 31188397.

88. Søndergaard MM, Hlatky MA, Stefanick ML, et al. Association of adverse pregnancy outcomes with risk of atherosclerotic cardiovascular disease in postmenopausal women. JAMA Cardiol. 2020; 5:1390–1398. PMID: 32936228.

89. Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia. 2019; 62:905–914. PMID: 30843102.

90. Crump C, Sundquist J, Howell EA, McLaughlin MA, Stroustrup A, Sundquist K. Pre-term delivery and risk of ischemic heart disease in women. J Am Coll Cardiol. 2020; 76:57–67. PMID: 32616164.

91. Li W, Ruan W, Lu Z, Wang D. Parity and risk of maternal cardiovascular disease: a dose-response meta-analysis of cohort studies. Eur J Prev Cardiol. 2019; 26:592–602. PMID: 30567461.

92. Vladutiu CJ, Siega-Riz AM, Sotres-Alvarez D, et al. Parity and components of the metabolic syndrome among US Hispanic/Latina women: results from the Hispanic Community Health Study/Study of Latinos. Circ Cardiovasc Qual Outcomes. 2016; 9:S62–S69. PMID: 26908862.

93. Cho DH, Choi J, Kim MN, et al. Gender differences in the presentation of chest pain in obstructive coronary artery disease: results from the KoRean wOmen'S chest pain rEgistry. Korean J Intern Med. 2020; 35:582–592. PMID: 30879289.

94. Chen W, Woods SL, Puntillo KA. Gender differences in symptoms associated with acute myocardial infarction: a review of the research. Heart Lung. 2005; 34:240–247. PMID: 16027643.

95. Rubini Gimenez M, Reiter M, Twerenbold R, et al. Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction. JAMA Intern Med. 2014; 174:241–249. PMID: 24275751.

96. D’Antono B, Dupuis G, Fortin C, Arsenault A, Burelle D. Angina symptoms in men and women with stable coronary artery disease and evidence of exercise-induced myocardial perfusion defects. Am Heart J. 2006; 151:813–819. PMID: 16569540.

97. Devon HA, Rosenfeld A, Steffen AD, Daya M. Sensitivity, specificity, and sex differences in symptoms reported on the 13-item acute coronary syndrome checklist. J Am Heart Assoc. 2014; 3:e000586. PMID: 24695650.

98. Bairey Merz CN, Shaw LJ, Reis SE, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) study: part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006; 47:S21–S29. PMID: 16458167.

99. van Oosterhout RE, de Boer AR, Maas AH, Rutten FH, Bots ML, Peters SA. Sex differences in symptom presentation in acute coronary syndromes: a systematic review and meta-analysis. J Am Heart Assoc. 2020; 9:e014733. PMID: 32363989.

100. Mackay MH, Ratner PA, Johnson JL, Humphries KH, Buller CE. Gender differences in symptoms of myocardial ischaemia. Eur Heart J. 2011; 32:3107–3114. PMID: 21920968.

101. Philpott S, Boynton PM, Feder G, Hemingway H. Gender differences in descriptions of angina symptoms and health problems immediately prior to angiography: the ACRE study. Appropriateness of Coronary Revascularisation study. Soc Sci Med. 2001; 52:1565–1575. PMID: 11314852.

102. Arora G, Bittner V. Chest pain characteristics and gender in the early diagnosis of acute myocardial infarction. Curr Cardiol Rep. 2015; 17:5. PMID: 25618302.

103. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34:2949–3003. PMID: 23996286.

104. Mingels AM, Kimenai DM. Sex-related aspects of biomarkers in cardiac disease. Adv Exp Med Biol. 2018; 1065:545–564. PMID: 30051406.

105. Kimenai DM, Lindahl B, Jernberg T, Bekers O, Meex SJ, Eggers KM. Sex-specific effects of implementing a high-sensitivity troponin I assay in patients with suspected acute coronary syndrome: results from SWEDEHEART registry. Sci Rep. 2020; 10:15227. PMID: 32943674.

106. Jernberg T, James S, Lindahl B, et al. Natriuretic peptides in unstable coronary artery disease. Eur Heart J. 2004; 25:1486–1493. PMID: 15342167.

107. Chung J, Kim HL, Kim MA, et al. Sex differences in long-term clinical outcomes in patients hospitalized for acute heart failure: a report from the Korean Heart Failure Registry. J Womens Health (Larchmt). 2019; 28:1606–1613. PMID: 31216207.

108. Kim HL, Kim MA, Choi DJ, et al. Gender difference in the prognostic value of N-terminal pro-B type natriuretic peptide in patients with heart failure- a report from the Korean Heart Failure Registry (KorHF). Circ J. 2017; 81:1329–1336. PMID: 28442636.

109. Slagman A, Searle J, Vollert JO, et al. Sex differences of troponin test performance in chest pain patients. Int J Cardiol. 2015; 187:246–251. PMID: 25838225.

110. Mieres JH, Gulati M, Bairey Merz N, et al. Role of noninvasive testing in the clinical evaluation of women with suspected ischemic heart disease: a consensus statement from the American Heart Association. Circulation. 2014; 130:350–379. PMID: 25047587.

111. De Bacquer D, De Backer G, Kornitzer M, Blackburn H. Prognostic value of ECG findings for total, cardiovascular disease, and coronary heart disease death in men and women. Heart. 1998; 80:570–577. PMID: 10065025.

112. Greenland P, Xie X, Liu K, et al. Impact of minor electrocardiographic ST-segment and/or T-wave abnormalities on cardiovascular mortality during long-term follow-up. Am J Cardiol. 2003; 91:1068–1074. PMID: 12714148.

113. Mieszczanska H, Pietrasik G, Piotrowicz K, McNitt S, Moss AJ, Zareba W. Gender-related differences in electrocardiographic parameters and their association with cardiac events in patients after myocardial infarction. Am J Cardiol. 2008; 101:20–24. PMID: 18157959.

114. Nowinski K, Jensen S, Lundahl G, Bergfeldt L. Changes in ventricular repolarization during percutaneous transluminal coronary angioplasty in humans assessed by QT interval, QT dispersion and T vector loop morphology. J Intern Med. 2000; 248:126–136. PMID: 10947891.

115. Cho DH, Choi J, Kim MN, et al. Incremental value of QT interval for the prediction of obstructive coronary artery disease in patients with chest pain. Sci Rep. 2021; 11:10513. PMID: 34006974.

116. Alexander KP, Shaw LJ, Shaw LK, Delong ER, Mark DB, Peterson ED. Value of exercise treadmill testing in women. J Am Coll Cardiol. 1998; 32:1657–1664. PMID: 9822093.

117. Kim YH, Shim WJ, Kim MA, et al. Utility of pretest probability and exercise treadmill test in Korean women with suspected coronary artery disease. J Womens Health (Larchmt). 2016; 25:617–622. PMID: 26562494.

118. Choi JO, Shin MS, Kim MJ, et al. Normal echocardiographic measurements in a Korean population study: part I. cardiac chamber and great artery evaluation. J Cardiovasc Ultrasound. 2015; 23:158–172. PMID: 26448824.

119. Mieres JH, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation. 2005; 111:682–696. PMID: 15687114.

120. Marwick TH, Shaw L, Case C, Vasey C, Thomas JD. Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice. Eur Heart J. 2003; 24:1153–1163. PMID: 12804930.

121. Kim MN, Kim SA, Kim YH, et al. Head to head comparison of stress echocardiography with exercise electrocardiography for the detection of coronary artery stenosis in women. J Cardiovasc Ultrasound. 2016; 24:135–143. PMID: 27358706.

122. Park SM, Kim MN, Kim SA, et al. Clinical significance of dynamic left ventricular outflow tract obstruction during dobutamine stress echocardiography in women with suspected coronary artery disease. Circ J. 2015; 79:2255–2262. PMID: 26255612.

123. Nguyen PK, Nag D, Wu JC. Sex differences in the diagnostic evaluation of coronary artery disease. J Nucl Cardiol. 2011; 18:144–152. PMID: 21136229.

124. Iorga A, Cunningham CM, Moazeni S, Ruffenach G, Umar S, Eghbali M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017; 8:33. PMID: 29065927.

125. Stamler J, Stamler R, Neaton JD, et al. Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women. JAMA. 1999; 282:2012–2018. PMID: 10591383.

126. Vasiljevic-Pokrajcic Z, Mickovski N, Davidovic G, et al. Sex and age differences and outcomes in acute coronary syndromes. Int J Cardiol. 2016; 217(Suppl):S27–S31. PMID: 27395070.

127. Mrdovic I, Savic L, Asanin M, et al. Sex-related analysis of short- and long-term clinical outcomes and bleeding among patients treated with primary percutaneous coronary intervention: an evaluation of the RISK-PCI data. Can J Cardiol. 2013; 29:1097–1103. PMID: 23462375.

128. Lin DS, Lin YS, Lee JK, Kao HL. Sex differences following percutaneous coronary intervention or coronary artery bypass surgery for acute myocardial infarction. Biol Sex Differ. 2022; 13:18. PMID: 35477482.

129. Guo Y, Yin F, Fan C, Wang Z. Gender difference in clinical outcomes of the patients with coronary artery disease after percutaneous coronary intervention: a systematic review and meta-analysis. Medicine (Baltimore). 2018; 97:e11644. PMID: 30045311.

130. Serruys PW, Cavalcante R, Collet C, et al. Outcomes after coronary stenting or bypass surgery for men and women with unprotected left main disease: the EXCEL trial. JACC Cardiovasc Interv. 2018; 11:1234–1243. PMID: 29976359.

131. Bryce Robinson N, Naik A, Rahouma M, et al. Sex differences in outcomes following coronary artery bypass grafting: a meta-analysis. Interact Cardiovasc Thorac Surg. 2021; 33:841–847. PMID: 34476494.

132. Lee SH, Choi J, Chang YJ, et al. Sex difference in long-term clinical outcomes after percutaneous coronary intervention: a propensity-matched analysis of National Health Insurance data in Republic of Korea. Catheter Cardiovasc Interv. 2021; 98:E171–E180. PMID: 33547718.

133. Park DW, Kim YH, Yun SC, et al. Sex difference in clinical outcomes after percutaneous coronary intervention in Korean population. Am Heart J. 2014; 167:743–752. PMID: 24766986.

134. Shin ES, Lee CW, Ahn JM, et al. Sex differences in left main coronary artery stenting: different characteristics but similar outcomes for women compared with men. Int J Cardiol. 2018; 253:50–54. PMID: 29306470.

135. Barthélémy O, Degrell P, Berman E, et al. Sex-related differences after contemporary primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Arch Cardiovasc Dis. 2015; 108:428–436. PMID: 25937358.

136. Takagi K, Chieffo A, Shannon J, et al. Impact of gender on long-term mortality in patients with unprotected left main disease: the Milan and New-Tokyo (MITO) Registry. Cardiovasc Revasc Med. 2016; 17:369–374. PMID: 27460302.

137. Shungin D, Winkler TW, Croteau-Chonka DC, et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015; 518:187–196. PMID: 25673412.

138. Kararigas G, Bito V, Tinel H, et al. Transcriptome characterization of estrogen-treated human myocardium identifies myosin regulatory light chain interacting protein as a sex-specific element influencing contractile function. J Am Coll Cardiol. 2012; 59:410–417. PMID: 22261164.

139. Goodarzynejad H, Boroumand M, Behmanesh M, Ziaee S, Jalali A. The rs5888 single nucleotide polymorphism in scavenger receptor class B type 1 (SCARB1) gene and the risk of premature coronary artery disease: a case-control study. Lipids Health Dis. 2016; 15:7. PMID: 26754576.

140. Hartiala JA, Tang WH, Wang Z, et al. Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease. Nat Commun. 2016; 7:10558. PMID: 26822151.

141. Ellis JA, Stebbing M, Harrap SB. Association of the human Y chromosome with high blood pressure in the general population. Hypertension. 2000; 36:731–733. PMID: 11082135.

142. Uehara Y, Shin WS, Watanabe T, et al. A hypertensive father, but not hypertensive mother, determines blood pressure in normotensive male offspring through body mass index. J Hum Hypertens. 1998; 12:441–445. PMID: 9702929.

143. Ng MK, Quinn CM, McCrohon JA, et al. Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females: molecular insights into gender differences in atherosclerosis. J Am Coll Cardiol. 2003; 42:1306–1313. PMID: 14522500.

144. Abraham G, Havulinna AS, Bhalala OG, et al. Genomic prediction of coronary heart disease. Eur Heart J. 2016; 37:3267–3278. PMID: 27655226.

145. Karalis DG, Wild RA, Maki KC, et al. Gender differences in side effects and attitudes regarding statin use in the Understanding Statin Use in America and Gaps in Patient Education (USAGE) study. J Clin Lipidol. 2016; 10:833–841. PMID: 27578114.

146. Smulyan H, Marchais SJ, Pannier B, Guerin AP, Safar ME, London GM. Influence of body height on pulsatile arterial hemodynamic data. J Am Coll Cardiol. 1998; 31:1103–1109. PMID: 9562014.

147. Kim HL, Lee Y, Lee JH, Shin JH, Shin J, Sung KC. Lack of the association between height and cardiovascular prognosis in hypertensive men and women: analysis of national real-world database. Sci Rep. 2022; 12:18953. PMID: 36347912.

148. Guimarães PO, Granger CB, Stebbins A, et al. Sex differences in clinical characteristics, psychosocial factors, and outcomes among patients with stable coronary heart disease: insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. J Am Heart Assoc. 2017; 6:e006695. PMID: 28912210.

149. Yang JJ, Yoon HS, Lee SA, et al. Metabolic syndrome and sex-specific socio-economic disparities in childhood and adulthood: the Korea National Health and Nutrition Examination Surveys. Diabet Med. 2014; 31:1399–1409. PMID: 24925795.

150. Wenger NK. Coronary heart disease: an older woman’s major health risk. BMJ. 1997; 315:1085–1090. PMID: 9366743.

151. Kaul P, Armstrong PW, Sookram S, Leung BK, Brass N, Welsh RC. Temporal trends in patient and treatment delay among men and women presenting with ST-elevation myocardial infarction. Am Heart J. 2011; 161:91–97. PMID: 21167339.

152. Möllmann H, Liebetrau C, Nef HM, Hamm CW. The Swedish paradox: or is there really no gender difference in acute coronary syndromes? Eur Heart J. 2011; 32:3070–3072. PMID: 22003153.

153. Truong QA, Murphy SA, McCabe CH, Armani A, Cannon CP. TIMI Study Group. Benefit of intensive statin therapy in women: results from PROVE IT-TIMI 22. Circ Cardiovasc Qual Outcomes. 2011; 4:328–336. PMID: 21487089.

154. Blomkalns AL, Chen AY, Hochman JS, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol. 2005; 45:832–837. PMID: 15766815.

155. Bugiardini R, Estrada JL, Nikus K, Hall AS, Manfrini O. Gender bias in acute coronary syndromes. Curr Vasc Pharmacol. 2010; 8:276–284. PMID: 19485901.

156. Zhao M, Woodward M, Vaartjes I, et al. Sex differences in cardiovascular medication prescription in primary care: a systematic review and meta-analysis. J Am Heart Assoc. 2020; 9:e014742. PMID: 32431190.

157. Ter Woorst JF, van Straten AH, Houterman S, Soliman-Hamad MA. Sex difference in coronary artery bypass grafting: preoperative profile and early outcome. J Cardiothorac Vasc Anesth. 2019; 33:2679–2684. PMID: 30928291.

158. Chen CY, Chuang SY, Fang CC, et al. Gender disparities in optimal lipid control among patients with coronary artery disease. J Atheroscler Thromb. 2014; 21(Suppl 1):S20–S28. PMID: 24452112.

159. Kim HJ, Kim HY, Kim HL, et al. Awareness of cardiovascular disease among Korean women: results from a nationwide survey. Prev Med Rep. 2022; 26:101698. PMID: 35111568.

160. Tannenbaum C, Norris CM, McMurtry MS. Sex-specific considerations in guidelines generation and application. Can J Cardiol. 2019; 35:598–605. PMID: 30910247.