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Journal of Cardiovascular Translational Research

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Open Access 01-02-2020 | Arterial Diseases | Review Article

Sex-Specific Aspects in the Pathophysiology and Imaging of Coronary Macro- and Microvascular Disease

Authors: Floor Groepenhoff, Sophie H. Bots, Elise L. Kessler, Ariane A. Sickinghe, Anouk L. M. Eikendal, Tim Leiner, Hester M. den Ruijter

Published in: Journal of Cardiovascular Translational Research | Issue 1/2020

Abstract

Sex differences in coronary artery disease (CAD) are well established, with women presenting with non-obstructive CAD more often than men do. However, recent evidence has identified coronary microvascular dysfunction as the underlying cause for cardiac complaints, yet sex-specific prevalence numbers are inconclusive. This review summarises known sex-specific aspects in the pathophysiology of both macro- and microvascular dysfunction and identifies currently existing knowledge gaps. In addition, this review describes current diagnostic approaches and whether these should take underlying sex differences into account by, for example, using different techniques or cut-off values for women and men. Future research into both innovation of imaging techniques and perfusion-related sex differences is needed to fill evidence gaps and enable the implementation of the available knowledge in daily clinical practice.

Parvand, M., Rayner-Hartley, E., & Sedlak, T. (2018). Recent developments in sex-related differences in presentation, prognosis, and management of coronary artery disease. Canadian Journal of Cardiology, 34(4), 390–399. https://doi.org/10.1016/j.cjca.2018.01.007.CrossRefPubMed

Izadnegahdar, M., Mackay, M., Lee, M. K., Sedlak, T. L., Gao, M., Bairey Merz, C. N., et al. (2016). Sex and ethnic differences in outcomes of acute coronary syndrome and stable angina patients with obstructive coronary artery disease. Circulation: Cardiovascular Quality and Outcomes, 9(2_suppl_1), S26–S35.

Gulati, M., Cooper-DeHoff, R. M., McClure, C., Johnson, B. D., Shaw, L. J., Handberg, E. M., et al. (2009). Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women’s Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Archives of Internal Medicine, 169(9), 843–850. https://doi.org/10.1001/archinternmed.2009.50.CrossRefPubMedPubMedCentral

Reis, S. E., Holubkov, R., Smith, A. C., Kelsey, S. F., Sharaf, B. L., Reichek, N., et al. (2001). Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. American Heart Journal, 141(5), 735–741.PubMed

Bairey Merz, C. N., Pepine, C. J., Walsh, M. N., Fleg, J. L., Camici, P. G., Chilian, W. M., et al. (2017). Ischemia and no obstructive coronary artery disease (INOCA) developing evidence-based therapies and research agenda for the next decade. Circulation, 135(11), 1075–1092.PubMed

Paul, T. K., Sivanesan, K., & Schulman-Marcus, J. (2017). Sex differences in nonobstructive coronary artery disease: recent insights and substantial knowledge gaps. Trends in Cardiovascular Medicine, 27(3), 173–179. https://doi.org/10.1016/j.tcm.2016.08.002.CrossRefPubMed

Montalescot, G., Sechtem, U., Achenbach, S., Andreotti, F., Arden, C., Budaj, A., et al. (2013). 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. European Heart Journal, 34(38), 2949–3003. https://doi.org/10.1093/eurheartj/eht296.CrossRefPubMed

Mathur, P., Ostadal, B., Romeo, F., & Mehta, J. L. (2015). Gender-related differences in atherosclerosis. Cardiovascular Drugs and Therapy, 29(4), 319–327. https://doi.org/10.1007/s10557-015-6596-3.CrossRefPubMed

Szego, C. M., & Davis, J. S. (1967). Adenosine 3′, 5′-monophosphate in rat uterus: acute elevation by estrogen. Proceedings of the National Academy of Sciences, 58(4), 1711–1718.

10.

Hogg, M. E., Vavra, A. K., Banerjee, M. N., Martinez, J., Jiang, Q., Keefer, L. K., et al. (2012). The role of estrogen receptor α and β in regulating vascular smooth muscle cell proliferation is based on Sex1. Journal of Surgical Research, 173(1), e1–e10.PubMed

11.

Yahagi, K., Davis, H. R., Arbustini, E., & Virmani, R. (2015). Sex differences in coronary artery disease: pathological observations. Atherosclerosis, 239(1), 260–267. https://doi.org/10.1016/j.atherosclerosis.2015.01.017.CrossRef

12.

Kataoka, Y., Puri, R., Hammadah, M., Duggal, B., Uno, K., Kapadia, S. R., et al. (2016). Sex differences in nonculprit coronary plaque microstructures on frequency-domain optical coherence tomography in acute coronary syndromes and stable coronary artery disease. Circulation: Cardiovascular Imaging, 9(8), e004506. https://doi.org/10.1161/CIRCIMAGING.116.004506.CrossRef

13.

Hellings, W. E., Pasterkamp, G., Verhoeven, B. A. N., De Kleijn, D. P. V., De Vries, J.-P. P. M., Seldenrijk, K. A., et al. (2007). Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomy. Journal of Vascular Surgery, 45(2), 289–296. https://doi.org/10.1016/j.jvs.2006.09.051.CrossRefPubMed

14.

Libby, P., Ridker, P. M., & Hansson, G. K. (2011). Progress and challenges in translating the biology of atherosclerosis. Nature, 473, 317. https://doi.org/10.1038/nature10146.CrossRefPubMed

15.

Hansen, L., & Taylor, W. R. (2016). Is increased arterial stiffness a cause or consequence of atherosclerosis? Atherosclerosis, 249, 226–227.PubMedPubMedCentral

16.

Fisher, N. D. L., & Curfman, G. (2018). Hypertension—a public health challenge of global proportions hypertension—a public health challenge of global proportions editorial. Jama, 320(17), 1757–1759. https://doi.org/10.1001/jama.2018.16760.CrossRefPubMed

17.

Regitz-Zagrosek, V., & Kararigas, G. (2017). Mechanistic pathways of sex differences in cardiovascular disease. Physiological Reviews, 97(1), 1–37. https://doi.org/10.1152/physrev.00021.2015.CrossRefPubMed

18.

Sullivan, A. K., Holdright, D. R., Wright, C. A., Sparrow, J. L., Cunningham, D., & Fox, K. M. (1994). Chest pain in women: clinical, investigative, and prognostic features. Bmj, 308(6933), 883–886.PubMedPubMedCentral

19.

Hvelplund, A., Galatius, S., Madsen, M., Rasmussen, J. N., Rasmussen, S., Madsen, J. K., et al. (2010). Women with acute coronary syndrome are less invasively examined and subsequently less treated than men. European Heart Journal, 31(6), 684–690. https://doi.org/10.1093/eurheartj/ehp493.CrossRef

20.

Shaw, J., & Anderson, T. (2016). Coronary endothelial dysfunction in non-obstructive coronary artery disease: risk, pathogenesis, diagnosis and therapy. Vascular Medicine, 21(2), 146–155.PubMed

21.

Camici, P. G., D’Amati, G., & Rimoldi, O. (2015). Coronary microvascular dysfunction: mechanisms and functional assessment. [Review]. Nature Reviews Cardiology, 12(1), 48–62. https://doi.org/10.1038/nrcardio.2014.160.CrossRefPubMed

22.

Murthy, V. L., Naya, M., Taqueti, V. R., Foster, C. R., Gaber, M., Hainer, J., et al. (2014). Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation, 129(24), 2518–2527. https://doi.org/10.1161/CIRCULATIONAHA.113.008507.CrossRefPubMedPubMedCentral

23.

Mygind, N. D., Michelsen, M. M., Pena, A., Frestad, D., Dose, N., Aziz, A., et al. (2016). Coronary microvascular function and cardiovascular risk factors in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study. Journal of the American Heart Association, 5(3), e003064.PubMedPubMedCentral

24.

Coutinho, T., Mielniczuk, L. M., Srivaratharajah, K., Wells, G. A., & Beanlands, R. S. (2018). Coronary artery microvascular dysfunction: role of sex and arterial load. International Journal of Cardiology, 270, 42–47.PubMed

25.

Baum, J., & Duffy, H. S. (2011). Fibroblasts and myofibroblasts: what are we talking about? Journal of Cardiovascular Pharmacology, 57(4), 376.PubMedPubMedCentral

26.

Suwanabol, P. A., Seedial, S. M., Shi, X., Zhang, F., Yamanouchi, D., Roenneburg, D., et al. (2012). Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated protein kinases pathways. Journal of Vascular Surgery, 56(2), 446–454 e441.PubMedPubMedCentral

27.

Sansone, R., Stanske, B., Keymel, S., Schuler, D., Horn, P., Saeed, D., et al. (2015). Macrovascular and microvascular function after implantation of left ventricular assist devices in end-stage heart failure: role of microparticles. The Journal of Heart and Lung Transplantation, 34(7), 921–932.PubMed

28.

Schwarzer, M., Osterholt, M., Lunkenbein, A., Schrepper, A., Amorim, P., & Doenst, T. (2014). Mitochondrial reactive oxygen species production and respiratory complex activity in rats with pressure overload-induced heart failure. The Journal of Physiology, 592(17), 3767–3782.PubMedPubMedCentral

29.

Dai, Z., Aoki, T., Fukumoto, Y., & Shimokawa, H. (2012). Coronary perivascular fibrosis is associated with impairment of coronary blood flow in patients with non-ischemic heart failure. Journal of Cardiology, 60(5), 416–421.PubMed

30.

Dworatzek, E., Mahmoodzadeh, S., Schriever, C., Kusumoto, K., Kramer, L., Santos, G., et al. (2018). Sex-specific regulation of collagen I and III expression by 17β-estradiol in cardiac fibroblasts: role of estrogen receptors. Cardiovascular Research, 115(2), 315–327.PubMedCentral

31.

Kong, P., Christia, P., & Frangogiannis, N. G. (2014). The pathogenesis of cardiac fibrosis. Cellular and Molecular Life Sciences, 71(4), 549–574.PubMed

32.

Oka, T., Akazawa, H., Naito, A. T., & Komuro, I. (2014). Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure. Circulation Research, 114(3), 565–571.PubMed

33.

Andrae, J., Gallini, R., & Betsholtz, C. (2008). Role of platelet-derived growth factors in physiology and medicine. Genes & Development, 22(10), 1276–1312.

34.

Chen, J.-X., Zeng, H., Reese, J., Aschner, J. L., & Meyrick, B. (2012). Overexpression of angiopoietin-2 impairs myocardial angiogenesis and exacerbates cardiac fibrosis in the diabetic db/db mouse model. American Journal of Physiology-Heart and Circulatory Physiology, 302(4), H1003.PubMed

35.

Dobaczewski, M., Chen, W., & Frangogiannis, N. G. (2011). Transforming growth factor (TGF)-β signaling in cardiac remodeling. Journal of Molecular and Cellular Cardiology, 51(4), 600–606.PubMed

36.

Jeansson, M., Gawlik, A., Anderson, G., Li, C., Kerjaschki, D., Henkelman, M., et al. (2011). Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. The Journal of Clinical Investigation, 121(6), 2278–2289.PubMedPubMedCentral

37.

Mahmoodzadeh, S., Leber, J., Zhang, X., Jaisser, F., Messaoudi, S., Morano, I., et al. (2014). Cardiomyocyte-specific estrogen receptor alpha increases angiogenesis, lymphangiogenesis and reduces fibrosis in the female mouse heart post-myocardial infarction. Journal of Cell Science & Therapy, 5(1), 153.

38.

Buteau-Lozano, H., Ancelin, M., Lardeux, B., Milanini, J., & Perrot-Applanat, M. (2002). Transcriptional regulation of vascular endothelial growth factor by estradiol and tamoxifen in breast cancer cells: a complex interplay between estrogen receptors α and β. Cancer Research, 62(17), 4977–4984.PubMed

39.

Mohammed, S. F., Hussain, S., Mirzoyev, S. A., Edwards, W. D., Maleszewski, J. J., & Redfield, M. M. (2015). Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation, 131(6), 550–559.PubMed

40.

Beale, A. L., Meyer, P., Marwick, T. H., Lam, C. S., & Kaye, D. M. (2018). Sex differences in cardiovascular pathophysiology: why women are overrepresented in heart failure with preserved ejection fraction. Circulation, 138(2), 198–205.PubMed

41.

Hwang, H. J., Chung, W. B., Park, J. H., Oh, S. S., Chung, J. W., Choi, Y. S., et al. (2010). Estimation of coronary flow velocity reserve using transthoracic Doppler echocardiography and cold pressor test might be useful for detecting of patients with variant angina. Echocardiography, 27(4), 435–441.PubMed

42.

Quyyumi, A. A., Dakak, N., Mulcahy, D., Andrews, N. P., Husain, S., Panza, J. A., et al. (1997). Nitric oxide activity in the atherosclerotic human coronary circulation. Journal of the American College of Cardiology, 29(2), 308–317.PubMed

43.

Al Jaroudi, W., & Iskandrian, A. E. (2009). Regadenoson: a new myocardial stress agent. Journal of the American College of Cardiology, 54(13), 1123–1130.PubMed

44.

Youn, H.-J., & Foster, E. (2004). Demonstration of coronary artery flow using transthoracic Doppler echocardiography. Journal of the American Society of Echocardiography, 17(2), 178–185.PubMed

45.

Kern, M. J., Lerman, A., Bech, J.-W., Bruyne, B. D., Eeckhout, E., Fearon, W. F., et al. (2006). Physiological assessment of coronary artery disease in the cardiac catheterization laboratory. Circulation, 114(12), 1321–1341. https://doi.org/10.1161/CIRCULATIONAHA.106.177276.CrossRefPubMed

46.

Fearon, W. F., Balsam, L. B., Farouque, H. O., Robbins, R. C., Fitzgerald, P. J., Yock, P. G., et al. (2003). Novel index for invasively assessing the coronary microcirculation. Circulation, 107(25), 3129–3132.PubMed

47.

Ng, M. K., Yeung, A. C., & Fearon, W. F. (2006). Invasive assessment of the coronary microcirculation: superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve. Circulation, 113(17), 2054–2061.PubMed

48.

Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., et al. (2015). Effect of sex differences on invasive measures of coronary microvascular dysfunction in patients with angina in the absence of obstructive coronary artery disease. JACC: Cardiovascular Interventions, 8(11), 1433–1441.PubMed

49.

van de Hoef, T. P., Bax, M., Meuwissen, M., Damman, P., Delewi, R., de Winter, R. J., et al. (2013). Impact of coronary microvascular function on long-term cardiac mortality in patients with acute ST-segment–elevation myocardial infarction. Circulation: Cardiovascular Interventions, 6(3), 207–215.PubMed

50.

Johnson, N. P., & Gould, K. L. (2011). Physiological basis for angina and ST-segment change: PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve. JACC: Cardiovascular Imaging, 4(9), 990–998.PubMed

51.

Kern, M. J. (2000). Coronary physiology revisited: practical insights from the cardiac catheterization laboratory. Circulation, 101(11), 1344–1351.PubMed

52.

Sara, J. D., Widmer, R. J., Matsuzawa, Y., Lennon, R. J., Lerman, L. O., & Lerman, A. (2015). Prevalence of coronary microvascular dysfunction among patients with chest pain and nonobstructive coronary artery disease. JACC: Cardiovascular Interventions, 8(11), 1445–1453. https://doi.org/10.1016/j.jcin.2015.06.017.CrossRefPubMed

53.

Opstal, T., Knol, R., Cornel, J., Wondergem, M., & van der Zant, F. (2018). Myocardial blood flow and myocardial flow reserve values in 13 N–ammonia myocardial perfusion PET/CT using a time-efficient protocol in patients without coronary artery disease. European Journal of Hybrid Imaging, 2(1), 11.

54.

De Bruyne, B., Pijls, N. H., Barbato, E., Bartunek, J., Bech, J.-W., Wijns, W., et al. (2003). Intracoronary and intravenous adenosine 5′-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation, 107(14), 1877–1883.PubMed

55.

Pijls, N. H. J., Bruyne, B. D., Smith, L., Aarnoudse, W., Barbato, E., Bartunek, J., et al. (2002). Coronary thermodilution to assess flow reserve. Circulation, 105(21), 2482–2486. https://doi.org/10.1161/01.CIR.0000017199.09457.3D.CrossRefPubMed

56.

Everaars, H., de Waard, G. A., Driessen, R. S., Danad, I., van de Ven, P. M., Raijmakers, P. G., et al. (2018). Doppler flow velocity and thermodilution to assess coronary flow reserve: a head-to-head comparison with [15O] H2O PET. JACC: Cardiovascular Interventions, 11(20), 2044–2054.PubMed

57.

Driessen, R. S., Raijmakers, P. G., Stuijfzand, W. J., & Knaapen, P. (2017). Myocardial perfusion imaging with PET. The International Journal of Cardiovascular Imaging, 33(7), 1021–1031.PubMedPubMedCentral

58.

Paulus, W. J., & Tschope, C. (2013). A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. Journal of the American College of Cardiology, 62(4), 263–271. https://doi.org/10.1016/j.jacc.2013.02.092.CrossRefPubMed

59.

Celeng, C., Leiner, T., Maurovich-Horvat, P., Merkely, B., de Jong, P., Dankbaar, J. W., et al. (2018). Anatomical and functional computed tomography for diagnosing hemodynamically significant coronary artery disease: a meta-analysis. JACC Cardiovasc Imaging. https://doi.org/10.1016/j.jcmg.2018.07.022.PubMed

60.

Nakazato, R., Heo, R., Leipsic, J., & Min, J. K. (2014). CFR and FFR assessment with PET and CTA: strengths and limitations. Current Cardiology Reports, 16(5), 484.PubMedPubMedCentral

61.

Caiati, C., Montaldo, C., Zedda, N., Montisci, R., Ruscazio, M., Lai, G., et al. (1999). Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire. Journal of the American College of Cardiology, 34(4), 1193–1200.PubMed

62.

Caiati, C., Zedda, N., Montaldo, C., Montisci, R., & Iliceto, S. (1999). Contrast-enhanced transthoracic second harmonic echo Doppler with adenosine: a noninvasive, rapid and effective method for coronary flow reserve assessment. Journal of the American College of Cardiology, 34(1), 122–130.PubMed

63.

Hozumi, T., Yoshida, K., Akasaka, T., Asami, Y., Ogata, Y., Takagi, T., et al. (1998). Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. Journal of the American College of Cardiology, 32(5), 1251–1259.PubMed

64.

Greenwood, J. P., Maredia, N., Younger, J. F., Brown, J. M., Nixon, J., Everett, C. C., et al. (2012). Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. The Lancet, 379(9814), 453–460.

65.

Liu, A., Wijesurendra, R. S., Liu, J. M., Forfar, J. C., Channon, K. M., Jerosch-Herold, M., et al. (2018). Diagnosis of microvascular angina using cardiac magnetic resonance. Journal of the American College of Cardiology, 71(9), 969–979.PubMedPubMedCentral

66.

Hung, O. Y., Lee, S. K., Eshtehardi, P., & Samady, H. (2016). Novel biomarkers of coronary microvascular disease. Future Cardiology, 12(4), 497–509.PubMedPubMedCentral

67.

Liu, A., Wijesurendra, R. S., Francis, J. M., Robson, M. D., Neubauer, S., Piechnik, S. K., et al. (2016). Adenosine stress and rest T1 mapping can differentiate between ischemic, infarcted, remote, and normal myocardium without the need for gadolinium contrast agents. JACC: Cardiovascular Imaging, 9(1), 27–36.PubMed

68.

Jerosch-Herold, M., Swingen, C., & Seethamraju, R. T. (2002). Myocardial blood flow quantification with MRI by model-independent deconvolution. Medical Physics, 29(5), 886–897.PubMed

69.

Gruber, B., Hendriks, A. D., Alborahal, C., Strijkers, G. J., Klomp, D. W. J., Leiner, T., et al. (2018). A 256-channel cardiac coil for accelerated cardiac imaging at 3 tesla - evaluation of a 32-channel prototype. 26, 4290.

70.

Wang, S., & Summers, R. M. (2012). Machine learning and radiology. Medical Image Analysis, 16(5), 933–951. https://doi.org/10.1016/j.media.2012.02.005.CrossRefPubMedPubMedCentral

71.

Moja, L., Kwag, K. H., Lytras, T., Bertizzolo, L., Brandt, L., Pecoraro, V., et al. (2014). Effectiveness of computerized decision support systems linked to electronic health records: a systematic review and meta-analysis. American Journal of Public Health, 104(12), e12–e22.PubMedPubMedCentral

72.

Buolamwini, J., & Gebru, T. (2018) Gender shades: intersectional accuracy disparities in commercial gender classification. In Conference on Fairness, Accountability and Transparency (pp. 77–91).

73.

Leavy, S. (2018) Gender bias in artificial intelligence: the need for diversity and gender theory in machine learning. In Proceedings of the 1st International Workshop on Gender Equality in Software Engineering (pp. 14–16): ACM.

74.

Worrall-Carter, L., McEvedy, S., Kuhn, L., Scruth, E., MacIsaac, A., & Rahman, M. A. (2017). Systematic review and meta-analyses investigating whether risk stratification explains lower rates of coronary angiography among women with non-ST-segment elevation acute coronary syndrome. The Journal of Cardiovascular Nursing, 32(2), 112–124. https://doi.org/10.1097/jcn.0000000000000300.CrossRefPubMed

75.

Dey, S., Flather, M. D., Devlin, G., Brieger, D., Gurfinkel, E. P., Steg, P. G., et al. (2009). Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the global registry of acute coronary events. Heart, 95(1), 20–26. https://doi.org/10.1136/hrt.2007.138537.CrossRefPubMed

76.

Rosano, G. M., Lewis, B., Agewall, S., Wassmann, S., Vitale, C., Schmidt, H., et al. (2015). Gender differences in the effect of cardiovascular drugs: a position document of the Working Group on Pharmacology and Drug Therapy of the ESC. European Heart Journal, 36(40), 2677–2680. https://doi.org/10.1093/eurheartj/ehv161.CrossRefPubMed

77.

Bots, S. H., Groepenhoff, F., Eikendal, A. L. M., Tannenbaum, C., Rochon, P. A., Regitz-Zagrosek, V., et al. (2019). Adverse drug reactions to guideline-recommended heart failure drugs in women. A Systematic Review of the Literature, 7(3), 258–266. https://doi.org/10.1016/j.jchf.2019.01.009.CrossRef

78.

Taqueti, V. R., & Di Carli, M. F. (2018). Coronary microvascular disease pathogenic mechanisms and therapeutic options. JACC State-of-the-Art Review, 72(21), 2625–2641. https://doi.org/10.1016/j.jacc.2018.09.042.CrossRef

79.

Verheye, S., Jolicoeur, E. M., Behan, M. W., Pettersson, T., Sainsbury, P., Hill, J., et al. (2015). Efficacy of a device to narrow the coronary sinus in refractory angina. The New England Journal of Medicine, 372(6), 519–527. https://doi.org/10.1056/NEJMoa1402556.CrossRefPubMedPubMedCentral

80.

Brainin, P., Frestad, D., & Prescott, E. (2018). The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease: a systematic review and meta-analysis. International Journal of Cardiology, 254, 1–9. https://doi.org/10.1016/j.ijcard.2017.10.052.CrossRefPubMed

81.

Indorkar, R., Kwong, R. Y., Romano, S., White, B. E., Chia, R. C., Trybula, M., et al. (2018). Global coronary flow reserve measured during stress cardiac magnetic resonance imaging is an independent predictor of adverse cardiovascular events. JACC: Cardiovascular Imaging, in press https://doi.org/10.1016/j.jcmg.2018.08.018.PubMed

82.

Lee, J. M., Jung, J. H., Hwang, D., Park, J., Fan, Y., Na, S. H., et al. (2016). Coronary flow reserve and microcirculatory resistance in patients with intermediate coronary stenosis. [article]. Journal of the American College of Cardiology, 67(10), 1158–1169. https://doi.org/10.1016/j.jacc.2015.12.053.CrossRefPubMed

83.

Dunlay, S. M., Roger, V. L., & Redfield, M. M. (2017). Epidemiology of heart failure with preserved ejection fraction. Nature Reviews. Cardiology, 14(10), 591–602. https://doi.org/10.1038/nrcardio.2017.65.CrossRefPubMed

84.

Shah, S. J., Katz, D. H., Selvaraj, S., Burke, M. A., Yancy, C. W., Gheorghiade, M., et al. (2015). Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation, 131(3), 269–279. https://doi.org/10.1161/circulationaha.114.010637.CrossRefPubMed

Title: Sex-Specific Aspects in the Pathophysiology and Imaging of Coronary Macro- and Microvascular Disease
Authors: Floor Groepenhoff
Sophie H. Bots
Elise L. Kessler
Ariane A. Sickinghe
Anouk L. M. Eikendal
Tim Leiner
Hester M. den Ruijter
Publication date: 01-02-2020
Publisher: Springer US
Keyword: Arterial Diseases
Published in: Journal of Cardiovascular Translational Research / Issue 1/2020
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-019-09906-0

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