National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore.
Department of Cardiology, the First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
Geroscience. 2024 Dec;46(6):5459-5471. doi: 10.1007/s11357-024-01127-x. Epub 2024 Mar 22.
Aging-induced aortic stiffness has been associated with altered fatty acid metabolism. We studied aortic stiffness using cardiac magnetic resonance (CMR)-assessed ventriculo-arterial coupling (VAC) and novel aortic (AO) global longitudinal strain (GLS) combined with targeted metabolomic profiling. Among community older adults without cardiovascular disease, VAC was calculated as aortic pulse wave velocity (PWV), a marker of arterial stiffness, divided by left ventricular (LV) GLS. AOGLS was the maximum absolute strain measured by tracking the phasic distance between brachiocephalic artery origin and aortic annulus. In 194 subjects (71 ± 8.6 years; 88 women), AOGLS (mean 5.6 ± 2.1%) was associated with PWV (R = -0.3644, p < 0.0001), LVGLS (R = 0.2756, p = 0.0001) and VAC (R = -0.3742, p <0.0001). Stiff aorta denoted by low AOGLS <4.26% (25 percentile) was associated with age (OR 1.13, 95% CI 1.04-1.24, p = 0.007), body mass index (OR 1.12, 95% CI 1.01-1.25, p = 0.03), heart rate (OR 1.04, 95% CI 1.01-1.06, p = 0.011) and metabolites of medium-chain fatty acid oxidation: C8 (OR 1.005, p = 0.026), C10 (OR 1.003, p = 0.036), C12 (OR 1.013, p = 0.028), C12:2-OH/C10:2-DC (OR 1.084, p = 0.032) and C16-OH (OR 0.82, p = 0.006). VAC was associated with changes in long-chain hydroxyl and dicarboxyl carnitines. Multivariable models that included acyl-carnitine metabolites, but not amino acids, significantly increased the discrimination over clinical risk factors for prediction of AOGLS (AUC [area-under-curve] 0.73 to 0.81, p = 0.037) and VAC (AUC 0.78 to 0.87, p = 0.0044). Low AO GLS and high VAC were associated with altered medium-chain and long-chain fatty acid oxidation, respectively, which may identify early metabolic perturbations in aging-associated aortic stiffening. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.
衰老是导致主动脉僵硬的一个因素，它与脂肪酸代谢的改变有关。我们使用心脏磁共振（CMR）评估的心室-动脉耦合（VAC）和新的主动脉（AO）整体纵向应变（GLS）以及靶向代谢组学分析来研究主动脉僵硬。在没有心血管疾病的社区老年人中，VAC 计算为主动脉脉搏波速度（PWV），即动脉僵硬的标志物，除以左心室（LV）GLS。AOGLS 是通过跟踪头臂动脉起源和主动脉瓣环之间的相位距离来测量的最大绝对应变。在 194 名受试者（71±8.6 岁；88 名女性）中，AOGLS（平均 5.6±2.1%）与 PWV（R=-0.3644，p<0.0001）、LVGLS（R=0.2756，p=0.0001）和 VAC（R=-0.3742，p<0.0001）相关。僵硬的主动脉由低 AOGLS<4.26%（25%分位数）表示，与年龄（OR 1.13，95%CI 1.04-1.24，p=0.007）、体重指数（OR 1.12，95%CI 1.01-1.25，p=0.03）、心率（OR 1.04，95%CI 1.01-1.06，p=0.011）和中链脂肪酸氧化的代谢物有关：C8（OR 1.005，p=0.026）、C10（OR 1.003，p=0.036）、C12（OR 1.013，p=0.028）、C12:2-OH/C10:2-DC（OR 1.084，p=0.032）和 C16-OH（OR 0.82，p=0.006）。VAC 与长链羟基和二羧酸肉碱的变化有关。包含酰基肉碱代谢物的多变量模型，但不包含氨基酸，显著提高了对 AOGLS（曲线下面积[AUC]0.73 至 0.81，p=0.037）和 VAC（AUC 0.78 至 0.87，p=0.0044）预测的区分度。低 AO GLS 和高 VAC 分别与中链和长链脂肪酸氧化的改变有关，这可能表明与衰老相关的主动脉僵硬中早期代谢紊乱。临床试验注册：ClinicalTrials.gov 标识符：NCT02791139。
