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
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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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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.
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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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DOI: https://doi.org/10.1007/s00392-023-02156-w