PMID- 35316808 OWN - NLM STAT- MEDLINE DCOM- 20230105 LR - 20230213 IS - 1423-0003 (Electronic) IS - 0304-324X (Print) IS - 0304-324X (Linking) VI - 69 IP - 1 DP - 2023 TI - Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways. PG - 47-56 LID - 10.1159/000522632 [doi] AB - INTRODUCTION: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. METHODS: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (epsilons), conduit strain (epsilone), and booster strain (epsilona) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. RESULTS: We studied 243 community adults (42.8% female, mean age 70.3 +/- 9.5 years). In bivariate analysis, epsilone and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 +/- 1.6 vs. 1.7 +/- 1.3, p = 0.0005), in those with >/=2 risk factors (3.3 +/- 2.4 vs. 1.7 +/- 1.3, p < 0.0001), compared to young adults; including between older adults with >/=2 risk factors and older adults with <2 risk factors (3.3 +/- 2.4 vs. 2.5 +/- 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both epsilone (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and epsilone reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of epsilone from 0.72 to 0.77 (p = 0.015). CONCLUSION: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes. CI - The Author(s). Published by S. Karger AG, Basel. FAU - Koh, Angela S AU - Koh AS AD - National Heart Centre Singapore, Singapore, Singapore. AD - Duke-NUS Medical School, Singapore, Singapore. FAU - Siau, Anthony AU - Siau A AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. FAU - Gao, Fei AU - Gao F AD - National Heart Centre Singapore, Singapore, Singapore. AD - Duke-NUS Medical School, Singapore, Singapore. FAU - Chioh, Florence W J AU - Chioh FWJ AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. FAU - Leng, Shuang AU - Leng S AD - National Heart Centre Singapore, Singapore, Singapore. FAU - Zhao, Xiaodan AU - Zhao X AD - National Heart Centre Singapore, Singapore, Singapore. FAU - Zhong, Liang AU - Zhong L AD - National Heart Centre Singapore, Singapore, Singapore. AD - Duke-NUS Medical School, Singapore, Singapore. FAU - Tan, Ru San AU - Tan RS AD - National Heart Centre Singapore, Singapore, Singapore. AD - Duke-NUS Medical School, Singapore, Singapore. FAU - Koh, Poh Ling AU - Koh PL AD - Duke-NUS Medical School, Singapore, Singapore. FAU - Kovalik, Jean-Paul AU - Kovalik JP AD - Duke-NUS Medical School, Singapore, Singapore. AD - Singapore General Hospital, Singapore, Singapore. FAU - Lim, Wee Shiong AU - Lim WS AD - Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, Singapore, Singapore. FAU - Lee, Gina S AU - Lee GS AD - National Heart Centre Singapore, Singapore, Singapore. FAU - Koh, Woon-Puay AU - Koh WP AD - Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore. FAU - Cheung, Christine AU - Cheung C AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. AD - Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore. LA - eng GR - R01 CA144034/CA/NCI NIH HHS/United States GR - UM1 CA182876/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220322 PL - Switzerland TA - Gerontology JT - Gerontology JID - 7601655 RN - 0 (Receptors, Urokinase Plasminogen Activator) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Humans MH - Female MH - Aged MH - Male MH - *Receptors, Urokinase Plasminogen Activator MH - *Atrial Fibrillation MH - Atrial Function, Left/physiology MH - Cross-Sectional Studies MH - Matrix Metalloproteinase 9 PMC - PMC9492896 MID - NIHMS1788796 OTO - NOTNLM OT - Aging OT - Biomarkers OT - Cardiovascular OT - Left atrium OT - Mechanisms COIS- No conflicts of interest. EDAT- 2022/03/23 06:00 MHDA- 2023/01/06 06:00 PMCR- 2022/03/22 CRDT- 2022/03/22 20:10 PHST- 2021/09/08 00:00 [received] PHST- 2022/02/15 00:00 [accepted] PHST- 2022/03/23 06:00 [pubmed] PHST- 2023/01/06 06:00 [medline] PHST- 2022/03/22 20:10 [entrez] PHST- 2022/03/22 00:00 [pmc-release] AID - 000522632 [pii] AID - ger-0069-0047 [pii] AID - 10.1159/000522632 [doi] PST - ppublish SO - Gerontology. 2023;69(1):47-56. doi: 10.1159/000522632. Epub 2022 Mar 22.