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Adverse cardiovascular and metabolic perturbations among older women: ‘fat-craving’ hearts

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Abstract

Background

Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women.

Methods

A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined.

Results

Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m2 vs 24 ± 3.4 kg/m2, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e′ ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e′ ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002–1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006–1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002–1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013–1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009–1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004–1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067–1.684, p = 0.012).

Conclusion

Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.

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Data availability statement

The data underlying this article cannot be shared publicly due to institutional restrictions. The data will be shared on reasonable request to the corresponding author.

Abbreviations

A′:

Peak tissue velocity of the mitral annulus in late diastole

AO:

Ascending aorta diameter

CI:

Confidence interval

DT:

Deceleration time

E′:

Peak tissue velocity of the mitral annulus in early diastole

E/A ratio:

Ratio of mitral E peak to mitral A peak

E/e′ ratio:

Ratio of mitral E peak to e'

IVRT:

Isovolumetric relaxation time

IVSd:

Interventricular septum thickness in diastole

IVSs:

Interventricular septum thickness in systole

LA:

Left atrium

LAVI:

Left atrium volume index

LV:

Left ventricle

LVEF:

Left ventricular ejection fraction

LVIDd:

Left ventricle internal diameter in diastole

LVIDs:

Left ventricle internal diameter in systole

LVMI:

Left ventricle mass index

LVOT:

Left ventricle outflow tract

LVPWd:

Left ventricle posterior wall thickness in diastole

LVPWs:

Left ventricle posterior wall thickness in systole

Mitral A peak:

Peak transmitral velocity in late diastole

Mitral E peak:

Peak transmitral velocity in early diastole

PASP:

Pulmonary artery systolic pressure

S′:

Peak tissue velocity of the mitral annulus in systole

References

  1. Merz AA, Cheng S (2016) Sex differences in cardiovascular ageing. Heart 102(11):825. https://doi.org/10.1136/heartjnl-2015-308769

    Article  PubMed  Google Scholar 

  2. Hayward CS, Kelly RP, Collins P (2000) The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc Res 46(1):28–49. https://doi.org/10.1016/s0008-6363(00)00005-5

    Article  CAS  PubMed  Google Scholar 

  3. Swaraj S, Kozor R, Arnott C, Di Bartolo BA, Figtree GA (2021) Heart failure with reduced ejection fraction-does sex matter? Curr Heart Fail Rep 18(6):345–352. https://doi.org/10.1007/s11897-021-00533-y

    Article  PubMed  PubMed Central  Google Scholar 

  4. Oktay AA, Rich JD, Shah SJ (2013) The emerging epidemic of heart failure with preserved ejection fraction. Curr Heart Fail Rep 10(4):401–410. https://doi.org/10.1007/s11897-013-0155-7

    Article  PubMed  Google Scholar 

  5. Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA (2005) Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation 112(15):2254–2262. https://doi.org/10.1161/CIRCULATIONAHA.105.541078

    Article  PubMed  Google Scholar 

  6. Pauls SD et al (2021) Impact of age, menopause, and obesity on oxylipins linked to vascular health. Arterioscler Thromb Vasc Biol 41(2):883–897. https://doi.org/10.1161/ATVBAHA.120.315133

    Article  CAS  PubMed  Google Scholar 

  7. Huang T et al (2019) Habitual sleep quality, plasma metabolites and risk of coronary heart disease in post-menopausal women. Int J Epidemiol 48(4):1262–1274. https://doi.org/10.1093/ije/dyy234

    Article  PubMed  Google Scholar 

  8. Campesi I et al (2016) Ageing/menopausal status in healthy women and ageing in healthy men differently affect cardiometabolic parameters. Int J Med Sci 13(2):124–132. https://doi.org/10.7150/ijms.14163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Auro K et al (2014) A metabolic view on menopause and ageing. Nat Commun 5(1):4708. https://doi.org/10.1038/ncomms5708

    Article  CAS  PubMed  Google Scholar 

  10. Shah SH, Newgard CB (2015) Integrated metabolomics and genomics. Circ Cardiovasc Genet 8(2):410–419. https://doi.org/10.1161/CIRCGENETICS.114.000223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fujimoto N et al (2012) Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans. J Physiol 590(8):1871–1880. https://doi.org/10.1113/jphysiol.2011.218271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shah SJ et al (2020) Research priorities for heart failure with preserved ejection fraction. Circulation 141(12):1001–1026. https://doi.org/10.1161/CIRCULATIONAHA.119.041886

    Article  PubMed  PubMed Central  Google Scholar 

  13. Vogel MW, Slusser JP, Hodge DO, Chen HH (2012) The natural history of preclinical diastolic dysfunction: a population-based study. Circ Heart Fail 5(2):144–151. https://doi.org/10.1161/CIRCHEARTFAILURE.110.959668

    Article  PubMed  PubMed Central  Google Scholar 

  14. Strait JB, Lakatta EG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8(1):143–164. https://doi.org/10.1016/j.hfc.2011.08.011

    Article  PubMed  PubMed Central  Google Scholar 

  15. From AM, Scott CG, Chen HH (2010) The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol 55(4):300–305. https://doi.org/10.1016/j.jacc.2009.12.003

    Article  PubMed  Google Scholar 

  16. Kovalik JP et al (2021) Amino acid differences between diabetic older adults and non-diabetic older adults and their associations with cardiovascular function. J Mol Cell Cardiol 158:63–71. https://doi.org/10.1016/j.yjmcc.2021.05.009

    Article  CAS  PubMed  Google Scholar 

  17. Hankin JH et al (2001) Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire. Nutr Cancer 39(2):187–195. https://doi.org/10.1207/S15327914nc392_5

    Article  CAS  PubMed  Google Scholar 

  18. Denchev SV, Simova II, Matveev MG (2007) Evaluation of the SCHILLER BR-102 plus noninvasive ambulatory blood pressure monitor according to the International Protocol introduced by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension. Blood Press Monit 12(5):329–333. https://doi.org/10.1097/MBP.0b013e32813fa39e

    Article  PubMed  Google Scholar 

  19. Nes BM, Janszky I, Vatten LJ, Nilsen TI, Aspenes ST, Wisløff U (2011) Estimating V·O 2peak from a nonexercise prediction model: the HUNT Study, Norway. Med Sci Sports Exerc 43(11):2024–2030. https://doi.org/10.1249/MSS.0b013e31821d3f6f

    Article  PubMed  Google Scholar 

  20. Nes BM, Vatten LJ, Nauman J, Janszky I, Wisløff U (2014) A simple nonexercise model of cardiorespiratory fitness predicts long-term mortality. Med Sci Sports Exerc 46(6):1159–1165. https://doi.org/10.1249/mss.0000000000000219

    Article  PubMed  Google Scholar 

  21. Koh AS et al (2018) Metabolomic correlates of aerobic capacity among elderly adults. Clin Cardiol 41(10):1300–1307. https://doi.org/10.1002/clc.23016

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lang RM et al (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28(1):1–39. https://doi.org/10.1016/j.echo.2014.10.003

    Article  PubMed  Google Scholar 

  23. Gao F et al (2021) Exacerbation of cardiovascular ageing by diabetes mellitus and its associations with acyl-carnitines. Aging 13(11):14785–14805. https://doi.org/10.18632/aging.203144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Upadhya B, Kitzman DW (2017) Heart failure with preserved ejection fraction in older adults. Heart Fail Clin 13(3):485–502. https://doi.org/10.1016/j.hfc.2017.02.005

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kobak KA, Zarzycka W, Chiao YA (2022) Age and sex differences in heart failure with preserved ejection fraction. Front Aging. https://doi.org/10.3389/fragi.2022.811436

    Article  PubMed  PubMed Central  Google Scholar 

  26. Paulus WJ et al (2007) How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28(20):2539–2550

    Article  PubMed  Google Scholar 

  27. Eaton CB et al (2016) Risk factors for incident hospitalized heart failure with preserved versus reduced ejection fraction in a multiracial cohort of postmenopausal women. Circ Heart Fail. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002883

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hunter WG et al (2016) Metabolomic profiling identifies novel circulating biomarkers of mitochondrial dysfunction differentially elevated in heart failure with preserved versus reduced ejection fraction: evidence for shared metabolic impairments in clinical heart failure. J Am Heart Assoc. https://doi.org/10.1161/jaha.115.003190

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cheng ML et al (2015) Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol 65(15):1509–1520. https://doi.org/10.1016/j.jacc.2015.02.018

    Article  CAS  PubMed  Google Scholar 

  30. Koh AS et al (2018) Dissecting clinical and metabolomics associations of left atrial phasic function by cardiac magnetic resonance feature tracking. Sci Rep 8(1):8138–8138. https://doi.org/10.1038/s41598-018-26456-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rinaldo P, Cowan TM, Matern D (2008) Acylcarnitine profile analysis. Genet Med 10(2):151–156. https://doi.org/10.1097/GIM.0b013e3181614289

    Article  PubMed  Google Scholar 

  32. Makrecka-Kuka M et al (2017) Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues. Sci Rep 7(1):17528. https://doi.org/10.1038/s41598-017-17797-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Molina AJ et al (2016) Skeletal muscle mitochondrial content, oxidative capacity, and Mfn2 expression are reduced in older patients with heart failure and preserved ejection fraction and are related to exercise intolerance. JACC Heart Fail 4(8):636–645. https://doi.org/10.1016/j.jchf.2016.03.011

    Article  PubMed  PubMed Central  Google Scholar 

  34. Rutkowsky JM et al (2014) Acylcarnitines activate proinflammatory signaling pathways. Am J Physiol Endocrinol Metab 306(12):E1378–E1387. https://doi.org/10.1152/ajpendo.00656.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Koh A et al (2017) Metabolomic profile of arterial stiffness in aged adults. Diab Vasc Dis Res 15:147916411773362. https://doi.org/10.1177/1479164117733627

    Article  CAS  Google Scholar 

  36. van der Zwaard S et al (2016) Maximal oxygen uptake is proportional to muscle fiber oxidative capacity, from chronic heart failure patients to professional cyclists. J Appl Physiol (1985) 121(3):636–645. https://doi.org/10.1152/japplphysiol.00355.2016

    Article  CAS  PubMed  Google Scholar 

  37. Betik AC, Hepple RT (2008) Determinants of VO2 max decline with aging: an integrated perspective. Appl Physiol Nutr Metab 33(1):130–140. https://doi.org/10.1139/h07-174

    Article  PubMed  Google Scholar 

  38. Magkos F et al (2013) Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabolism. Diabetes 62(8):2757–2761. https://doi.org/10.2337/db13-0185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chng CL et al (2016) Physiological and metabolic changes during the transition from hyperthyroidism to euthyroidism in graves’ disease. Thyroid 26(10):1422–1430. https://doi.org/10.1089/thy.2015.0602

    Article  CAS  PubMed  Google Scholar 

  40. Bao XR et al (2016) Mitochondrial dysfunction remodels one-carbon metabolism in human cells. Elife. https://doi.org/10.7554/eLife.10575

    Article  PubMed  PubMed Central  Google Scholar 

  41. Razavi AC et al (2020) Novel findings from a metabolomics study of left ventricular diastolic function: the Bogalusa heart study. J Am Heart Assoc 9(3):e015118. https://doi.org/10.1161/JAHA.119.015118

    Article  PubMed  PubMed Central  Google Scholar 

  42. Previtali M, Chieffo E, Ferrario M, Klersy C (2012) Is mitral E/E′ ratio a reliable predictor of left ventricular diastolic pressures in patients without heart failure? European Heart Journal - Cardiovascular Imaging 13(7):588–595. https://doi.org/10.1093/ejechocard/jer286

    Article  PubMed  Google Scholar 

  43. Sharp AS et al (2010) Tissue Doppler E/E’ ratio is a powerful predictor of primary cardiac events in a hypertensive population: an ASCOT substudy. Eur Heart J 31(6):747–752. https://doi.org/10.1093/eurheartj/ehp498

    Article  PubMed  Google Scholar 

  44. Kim HL et al (2013) The association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population. Cardiovasc Ultrasound 11(1):2. https://doi.org/10.1186/1476-7120-11-2

    Article  PubMed  PubMed Central  Google Scholar 

  45. H-L Kim et al (2017) Association between arterial stiffness and left ventricular diastolic function in relation to gender and age. Medicine 96(1) [Online]. https://journals.lww.com/md-journal/Fulltext/2017/01060/Association_between_arterial_stiffness_and_left.47.aspx.

  46. Wu J, Yu SY, Wo D, Zhao MM, Zhang LJ, Li J (2016) Risks and predictors of mild diastolic dysfunction among middle-aged and aged women: a population-based cohort study. J Hum Hypertens 30(5):335–340. https://doi.org/10.1038/jhh.2015.85

    Article  CAS  PubMed  Google Scholar 

  47. Zhao Z, Wang H, Jessup JA, Lindsey SH, Chappell MC, Groban L (2014) Role of estrogen in diastolic dysfunction. American Journal of Physiology-Heart and Circulatory Physiology 306(5):H628–H640. https://doi.org/10.1152/ajpheart.00859.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mathew S et al (2014) Metabolomics of Ramadan fasting: an opportunity for the controlled study of physiological responses to food intake. J Transl Med 12:161. https://doi.org/10.1186/1479-5876-12-161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Carayol M et al (2015) Reliability of serum metabolites over a two-year period: a targeted metabolomic approach in fasting and non-fasting samples from EPIC. PLoS ONE 10(8):e0135437. https://doi.org/10.1371/journal.pone.0135437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hancox RJ, Landhuis CE (2011) Correlation between measures of insulin resistance in fasting and non-fasting blood. Diabetol Metab Syndr 3(1):23. https://doi.org/10.1186/1758-5996-3-23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wallace TM, Matthews DR (2002) The assessment of insulin resistance in man. Diabet Med. https://doi.org/10.1046/j.1464-5491.2002.00745.x

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank staff and collaborators from the imaging and research laboratories for participating in the conduct of the study.

Funding

The Cardiac Aging Study has received funding support from the National Medical Research Council of Singapore (MOH-000153, HLCA21Jan-0052), Hong Leong Foundation, Duke-NUS Medical School, Estate of Tan Sri Khoo Teck Puat and Singhealth Foundation. Woon-Puay Koh is supported by the National Medical Research Council, Singapore (MOH-CSASI19nov-0001). The funders had no role in the design and conduct of the study; collection; management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

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Author notes

  1. Jien Sze Ho and Jie Jun Wong have contributed equally.

Authors and Affiliations

  1. National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore

    Jien Sze Ho, Jie Jun Wong, Fei Gao, Louis L. Y. Teo, See Hooi Ewe, Ru-San Tan & Angela S. Koh

  2. Duke-NUS Medical School, Singapore, Singapore

    Jien Sze Ho, Fei Gao, Hai Ning Wee, Louis L. Y. Teo, See Hooi Ewe, Ru-San Tan, Jianhong Ching, Kee Voon Chua, Lye Siang Lee, Jean-Paul Kovalik & Angela S. Koh

  3. KK Research Centre, KK Women’s and Children’s Hospital, Singapore, Singapore

    Jianhong Ching

  4. Singapore General Hospital, Singapore, Singapore

    Jean-Paul Kovalik

  5. Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Woon-Puay Koh

  6. Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore

    Woon-Puay Koh

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  1. Jien Sze Ho
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Contributions

ASK, J-PK, LLYT, SHE, R-ST, W-PK contributed to the conception and design of the work. FG, WHN, ASK, JC, KVC, LSL contributed to the acquisition, analysis and interpretation of the data. The first draft of the manuscript was written by JSH and JJW. All authors have participated in reviewing and/or revising the manuscript and have approved its submission.

Corresponding author

Correspondence to Angela S. Koh.

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Ho, J.S., Wong, J.J., Gao, F. et al. Adverse cardiovascular and metabolic perturbations among older women: ‘fat-craving’ hearts. Clin Res Cardiol 112, 1555–1567 (2023). https://doi.org/10.1007/s00392-023-02156-w

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