Older women had better LV global longitudinal strain (-21.9% vs -20.1%, p=0.024) linked to higher serum aspartate and anabolic amino acids than men or women with poorer LVGLS.
Are sex differences in cellular biosynthesis and metabolism pathways associated with left ventricular global longitudinal strain preservation in older adults?
Sex differences in metabolism, specifically higher levels of certain amino acids in women, are linked to better preservation of left ventricular global longitudinal strain with aging.
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Abstract Background Sex differences in aging-related cardiac remodelling have been linked to the relative preservation of left ventricular (LV) systolic function among older women compared to men. Purpose We employed cardiovascular imaging with serum metabolomics to explore the cellular biosynthesis and metabolism pathways, with the aim of understanding the sex-based differences of myocardial aging. Methods Community older adults without cardiovascular disease underwent cardiovascular magnetic resonance to derive LV global longitudinal strain (LVGLS) and simultaneous serum metabolomics profiling. Multivariable logistic regression adjusted for significant baseline variables. Results Among 202 participants (46.0% women, 70.2±8.8 years), women had superior LVGLS (-21.9±2.6% vs -20.1±2.8% adj. p=0.024) compared to men, independent of smoking status, body habitus differences, and diastolic blood pressure. Women with better LVGLS were associated with less LV hypertrophy and smaller cardiac volumes than women with poorer LVGLS. Overall, better LVGLS was associated with higher serum aspartate levels (β=0.076, SE=0.033, adj. p=0.022). Women with better LVGLS had higher serum levels of methionine (26.4±10.4 vs. 19.3±4.2 adj. p=0.037), phenylalanine (78.5±16.2 μM vs 66.8±7.9 μM adj. p=0.029), arginine (113.7±28.7 μM vs 88.9±20.3 μM adj. p=0.018), and tyrosine (76.1±22.9 μM vs 60.9±15.9 μM adj. p=0.035) than women with poorer LVGLS. No amino acid differences were observed among men classified by LVGLS. Conclusions Better overall LVGLS was linked to higher serum aspartate, a key component of the malate-aspartate shuttle that supplies reducing equivalents to the mitochondria, suggesting greater fuel oxidation efficiency. Among women with better LVGLS, elevated tricarboxylic acid cycle substrate levels (e.g., methionine, arginine) suggest increased anaplerosis, providing carbon for biosynthetic activity. Higher levels of proteinogenic amino acids (e.g., phenylalanine, tyrosine) promote increased anabolic activity. Metabolism plays a vital role in maintaining cardiovascular health with aging. Sex differences in metabolism may explain variations in LVGLS preservation with aging and provide insights for future cardiovascular prevention strategies.Table A Figure A
Wong et al. (Sat,) reported a other. Older women had better LV global longitudinal strain (-21.9% vs -20.1%, p=0.024) linked to higher serum aspartate and anabolic amino acids than men or women with poorer LVGLS.