Sex differences in cardiovascular pathophysiology why women are overrepresented in heart failure with preserved ejection fraction

Circulation

Volumn 138, Issue 2, 2018, Pages 198-205

  Beale, Anna L ^a,b,c,d   Meyer, Philippe M D ^d   Marwick, Thomas H ^a,b   Lam, Carolyn S P ^e,f   Kaye, David M ^a,b,c  

^a BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^b ALFRED HOSPITAL   (Australia)

^c MONASH UNIVERSITY   (Australia)

^d GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^e DEPARTMENT OF CARDIOLOGY   (Singapore)

^f UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Heart failure; Myocardium; Sex factors; Vascular stiffness; Women

Indexed keywords

ARTICLE; ATRIAL FIBRILLATION; AUTOIMMUNE DISEASE; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR RISK; CARDIOVASCULAR SYSTEM; COMORBIDITY; CORONARY ARTERY DISEASE; DIABETES MELLITUS; DISEASE PREDISPOSITION; FEMALE; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART FUNCTION; HEART MUSCLE METABOLISM; HUMAN; HYPERTENSION; IMMUNE SYSTEM; INFLAMMATION; IRON DEFICIENCY; LUNG CIRCULATION; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; PREECLAMPSIA; PREGNANCY; PRIORITY JOURNAL; SEX DIFFERENCE; SYSTEMIC CIRCULATION; HEART FAILURE; HEART STROKE VOLUME; MALE; PHYSIOLOGY; PREVALENCE; RISK FACTOR; SEX FACTOR; SEXUAL CHARACTERISTICS;

CARDIOVASCULAR SYSTEM; FEMALE; HEART FAILURE; HUMANS; MALE; PREVALENCE; RISK FACTORS; SEX CHARACTERISTICS; SEX FACTORS; STROKE VOLUME;

EID: 85056411241     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.118.034271     Document Type: Article

References (53)

1. Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14:591–602. doi: 10.1038/nrcardio.2017.65.
2. Ho JE, Gona P, Pencina MJ, Tu JV, Austin PC, Vasan RS, Kannel WB, D’Agostino RB, Lee DS, Levy D. Discriminating clinical features of heart failure with preserved vs. reduced ejection fraction in the community. Eur Heart J. 2012;33:1734–1741. doi: 10.1093/eurheartj/ehs070.
3. Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA. Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation. 2005;112:2254–2262. doi: 10.1161/CIRCULATIONAHA.105.541078.
4. Chung AK, Das SR, Leonard D, Peshock RM, Kazi F, Abdullah SM, Can-ham RM, Levine BD, Drazner MH. Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study. Circulation. 2006;113:1597–1604. doi: 10.1161/CIRCULATIONAHA.105.574400.
5. Föll D, Jung B, Schilli E, Staehle F, Geibel A, Hennig J, Bode C, Markl M. Magnetic resonance tissue phase mapping of myocardial motion: new insight in age and gender. Circ Cardiovasc Imaging. 2010;3:54–64. doi: 10.1161/CIRCIMAGING.108.813857.
6. Kajstura J, Gurusamy N, Ogórek B, Goichberg P, Clavo-Rondon C, Hosoda T, D’Amario D, Bardelli S, Beltrami AP, Cesselli D, Bussani R, del Monte F, Quaini F, Rota M, Beltrami CA, Buchholz BA, Leri A, Anversa P. Myocyte turnover in the aging human heart. Circ Res. 2010;107:1374–1386. doi: 10.1161/CIRCRESAHA.110.231498.
7. Gori M, Lam CS, Gupta DK, Santos AB, Cheng S, Shah AM, Claggett B, Zile MR, Kraigher-Krainer E, Pieske B, Voors AA, Packer M, Bransford T, Lefkowitz M, McMurray JJ, Solomon SD; PARAMOUNT Investigators. Sex-specific cardiovascular structure and function in heart failure with preserved ejection fraction. Eur J Heart Fail. 2014;16:535–542. doi: 10.1002/ejhf.67.
8. Ha JW, Lee HC, Park S, Choi EY, Seo HS, Shim CY, Kim JM, Ahn JA, Lee SW, Rim SJ, Oh JK, Chung N. Gender-related difference in left ventricular diastolic elastance during exercise in patients with diabetes mellitus. Circ J. 2008;72:1443–1448.
9. Houstis NE, Lewis GD. Causes of exercise intolerance in heart failure with preserved ejection fraction: searching for consensus. J Card Fail. 2014;20:762–778. doi: 10.1016/j.cardfail.2014.07.010.
10. Nikitin NP, Witte KK, Thackray SD, Goodge LJ, Clark AL, Cleland JG. Effect of age and sex on left atrial morphology and function. Eur J Echocardiogr. 2003;4:36–42.
11. Zhao Z, Wang H, Jessup JA, Lindsey SH, Chappell MC, Groban L. Role of estrogen in diastolic dysfunction. Am J Physiol Heart Circ Physiol. 2014;306:H628–H640. doi: 10.1152/ajpheart.00859.2013.
12. Kravstov GM, Lam KWL, Liu J, Wu S and Wong TM. Altered Ca2+ handling by ryanodine receptor and Na+-Ca2+ exchange in the heart from ovariectomized rats: role of protein kinase A. Am J Physiol Cell Physiol. 2007;292:C1625–C1635. doi: 10.1152/ajpcell.00368.2006.
13. Chung E, Yeung F, Leinwand LA. Akt and MAPK signaling mediate pregnancy-induced cardiac adaptation. J Appl Physiol (1985). 2012;112:1564–1575. doi: 10.1152/japplphysiol.00027.2012.
14. Parks RJ, Ray G, Bienvenu LA, Rose RA, Howlett SE. Sex differences in SR Ca(2+) release in murine ventricular myocytes are regulated by the cAMP/PKA pathway. J Mol Cell Cardiol. 2014;75:162–173. doi: 10.1016/j.yjmcc.2014.07.006.
15. Peterson LR, Soto PF, Herrero P, Mohammed BS, Avidan MS, Schechtman KB, Dence C, Gropler RJ. Impact of gender on the myocardial metabolic response to obesity. J Am Coll Cardiol. Cardiovasc Imaging. 2008;1:424–433. doi: 10.1016/j.jcmg.2008.05.004.
16. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263–271. doi: 10.1016/j.jacc.2013.02.092.
17. Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015;131:550–559. doi: 10.1161/CIRCULATIONAHA.114.009625.
18. Russo C, Jin Z, Palmieri V, Homma S, Rundek T, Elkind MS, Sacco RL, Di Tul-lio MR. Arterial stiffness and wave reflection: sex differences and relationship with left ventricular diastolic function. Hypertension. 2012;60:362–368. doi: 10.1161/HYPERTENSIONAHA.112.191148.
19. Lam CS, Xanthakis V, Sullivan LM, Lieb W, Aragam J, Redfield MM, Mitchell GF, Benjamin EJ, Vasan RS. Aortic root remodeling over the adult life course: longitudinal data from the Framingham Heart Study. Circulation. 2010;122:884–890. doi: 10.1161/CIRCULATIONAHA.110.937839.
20. Hamburg NM, Palmisano J, Larson MG, Sullivan LM, Lehman BT, Vasan RS, Levy D, Mitchell GF, Vita JA, Benjamin EJ. Relation of brachial and digital measures of vascular function in the community: the Framingham heart study. Hypertension. 2011;57:390–396. doi: 10.1161/HYPERTENSIONAHA.110.160812.
21. Shim CY, Park S, Choi D, Yang WI, Cho IJ, Choi EY, Chung N, Ha JW. Sex differences in central hemodynamics and their relationship to left ventricular diastolic function. J Am Coll Cardiol. 2011;57:1226–1233. doi: 10.1016/j.jacc.2010.09.067.
22. Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, Redfield MM. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2010;56:845–854. doi: 10.1016/j.jacc.2010.03.077.
23. Dixon DD, Trivedi A, Shah SJ. Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction. Heart Fail Rev. 2016;21:285–297. doi: 10.1007/s10741-015-9523-6.
24. Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Turner M, Giles S, Feldkircher K, Miller DP, McGoon MD. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137:376–387. doi: 10.1378/chest.09-1140.
25. Thenappan T, Shah SJ, Gomberg-Maitland M, Collander B, Vallakati A, Shroff P, Rich S. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ Heart Fail. 2011;4:257–265. doi: 10.1161/CIRCHEARTFAILURE.110.958801.
26. Fujimoto N, Borlaug BA, Lewis GD, Hastings JL, Shafer KM, Bhella PS, Car-rick-Ranson G, Levine BD. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation. 2013;127:55–62. doi: 10.1161/CIRCULATIONAHA.112.111302.
27. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275:1557–1562.
28. Chester R, Sander G, Fernandez C, Chen W, Berenson G, Giles T. Women have significantly greater difference between central and peripheral arterial pressure compared with men: the Bogalusa Heart Study. J Am Soc Hypertens. 2013;7:379–385. doi: 10.1016/j.jash.2013.05.007.
29. Higashi H, Okayama H, Saito M, Morioka H, Aono J, Yoshii T, Hiasa G, Sumimoto T, Nishimura K, Inoue K, Ogimoto A, Higaki J. Relationship between augmentation index and left ventricular diastolic function in healthy women and men. Am J Hypertens. 2013;26:1280–1286. doi: 10.1093/ajh/hpt115.
30. Kuch B, Muscholl M, Luchner A, Döring A, Riegger GA, Schunkert H, Hense HW. Gender specific differences in left ventricular adaptation to obesity and hypertension. J Hum Hypertens. 1998;12:685–691.
31. Merz AA, Cheng S. Sex differences in cardiovascular ageing. Heart. 2016;102:825–831. doi: 10.1136/heartjnl-2015-308769.
32. Crea F, Bairey Merz CN, Beltrame JF, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Camici PG; Coronary Vasomotion Disorders International Study Group (COVADIS). The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift. Eur Heart J. 2017;38:473–477. doi: 10.1093/eurheartj/ehw461.
33. Seidelmann SB, Claggett B, Bravo PE, Gupta A, Farhad H, Klein BE, Klein R, Di Carli M, Solomon SD. Retinal vessel calibers in predicting long-term cardiovascular outcomes: the Atherosclerosis Risk in Communities Study. Circulation. 2016;134:1328–1338. doi: 10.1161/CIRCULATIONAHA.116.023425.
34. Yoshida K, Obokata M, Kurosawa K, Sorimachi H, Kurabayashi M, Negishi K. Effect of sex differences on the association between stroke risk and left atrial anatomy or mechanics in patients with atrial fibrillation. Circ Cardiovasc Imaging. 2016;9:e004999. doi: 10.1161/CIRCIMAGING.116.004999.
35. Meyer S, Brouwers FP, Voors AA, Hillege HL, de Boer RA, Gansevoort RT, van der Harst P, Rienstra M, van Gelder IC, van Veldhuisen DJ, van Gilst WH, van der Meer P. Sex differences in new-onset heart failure. Clin Res Cardiol. 2015;104:342–350. doi: 10.1007/s00392-014-0788-x.
36. O’Neal WT, Sandesara P, Hammadah M, Venkatesh S, Samman-Tahhan A, Kelli HM, Soliman EZ. Gender differences in the risk of adverse outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction. Am J Cardiol. 2017;119:1785–1790. doi: 10.1016/j.amjcard.2017.02.045.
37. Aslam F, Bandeali SJ, Khan NA, Alam M. Diastolic dysfunction in rheumatoid arthritis: a meta-analysis and systematic review. Arthritis Care Res (Hoboken). 2013;65:534–543. doi: 10.1002/acr.21861.
38. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Im-munol. 2016;16:626–638. doi: 10.1038/nri.2016.90.
39. Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, Vongpatanasin W, Wians FH Jr, Grundy SM, de Lemos JA. Race and gender differences in C-reactive protein levels. J Am Coll Cardiol. 2005;46:464–469. doi: 10.1016/j.jacc.2005.04.051.
40. Inanloo Rahatloo K, Liang G, Vo D, Ebert A, Nguyen I, Nguyen PK. Sex-based differences in myocardial gene expression in recently deceased organ donors with no prior cardiovascular disease. PLoS One. 2017;12:e0183874. doi: 10.1371/journal.pone.0183874.
41. Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999;180(2 Pt 1):499–506.
42. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974;34:29–34.
43. Kim HL, Kim MA, Oh S, Kim M, Park SM, Yoon HJ, Shin MS, Hong KS, Shin GJ, Shim WJ. Sex difference in the association between metabolic syndrome and left ventricular diastolic dysfunction. Metab Syndr Relat Disord. 2016;14:507–512. doi: 10.1089/met.2016.0078.
44. Eaton CB, Pettinger M, Rossouw J, Martin LW, Foraker R, Quddus A, Liu S, Wampler NS, Hank Wu W-C, Manson JE, Margolis K, Johnson KC, Allison M, Corbie-Smith G, Rosamond W, Breathett K, Klein L. Risk factors for incident hospitalized heart failure with preserved versus reduced ejection fraction in a multiracial cohort of postmenopausal women. Circ Heart Fail. 2016;9:e002883.
45. Martens P, Nijst P, Verbrugge FH, Smeets K, Dupont M, Mullens W. Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction. Acta cardiol. 2017:1–9.
46. Macdougall IC, Canaud B, de Francisco AL, Filippatos G, Ponikowski P, Silverberg D, van Veldhuisen DJ, Anker SD. Beyond the cardiorenal anae-mia syndrome: recognizing the role of iron deficiency. Eur J Heart Fail. 2012;14:882–886. doi: 10.1093/eurjhf/hfs056.
47. Keskin M, Avşar Ş, Hayıroğlu Mİ, Keskin T, Börklü EB, Kaya A, Uzun AO, Akyol B, Güvenç TS, Kozan Ö. Relation of the number of parity to left ventricular diastolic function in pregnancy. Am J Cardiol. 2017;120:154–159. doi: 10.1016/j.amjcard.2017.03.244.
48. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias R, Rushton C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, Mamas MA. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10:e003497. doi: 10.1161/CIRCOUTCOMES. 116.003497.
49. Melchiorre K, Sharma R, Thilaganathan B. Cardiovascular implications in preeclampsia: an overview. Circulation. 2014;130:703–714. doi: 10.1161/CIRCULATIONAHA.113.003664.
50. Ho JE, Enserro D, Brouwers FP, Kizer JR, Shah SJ, Psaty BM, Bartz TM, Santhanakrishnan R, Lee DS, Chan C, Liu K, Blaha MJ, Hillege HL, van der Harst P, van Gilst WH, Kop WJ, Gansevoort RT, Vasan RS, Gardin JM, Levy D, Gottdiener JS, de Boer RA, Larson MG. Predicting heart failure with preserved and reduced ejection fraction: the international collaboration on heart failure subtypes. Circ Heart Fail. 2016;9:e003116. doi: 10.1161/ CIRCHEARTFAILURE.115.003116.
51. Biondi-Zoccai GG, Abate A, Bussani R, Camilot D, Giorgio FD, Marino MP, Silvestri F, Baldi F, Biasucci LM, Baldi A. Reduced post-infarction myocardial apoptosis in women: a clue to their different clinical course? Heart. 2005;91:99–101. doi: 10.1136/hrt.2003.018754.
52. Dunlay SM, Roger VL. Gender differences in the pathophysiology, clinical presentation, and outcomes of ischemic heart failure. Curr Heart Fail Rep. 2012;9:267–276. doi: 10.1007/s11897-012-0107-7.
53. Lam CS. What is normal in HFNEF?: The case for HFpEF. JACC Heart Fail. 2014;2:541–543. doi: 10.1016/j.jchf.2014.04.013.