老年人线粒体功能障碍和炎症的生物标志物与血压变异性

Leonardo Bencivenga, Mathilde Strumia, Yves Rolland, Sandrine Andrieu, Bruno Vellas, Philipe De Souto Barreto, Laure Rouch, for the MAPT/D. S. A. group
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摘要

目的:升高的血压变异性(BPV)可能代表了血压生理稳态模式的改变。BPV的大多数生理病理机制都与衰老有关。血管老化与晚年发生的慢性低度炎症有关,称为“炎症”,以及与年龄相关疾病引起的压力相关的标志性“线粒体功能障碍”,这反过来又可能导致BPV升高和心血管疾病的风险。我们的目的是确定多效性应激相关的分裂因子生长/分化因子15 (GDF-15)和两种炎症生物标志物白介素6 (IL-6)和肿瘤坏死因子受体1 (TNFR-1)的血浆水平是否与社区居住老年人的来访BPV相关。方法:研究人群包括1,096名参与者[中位年龄75(72-78)岁;从MAPT研究中选取年龄≥70岁的社区居住参与者699名女性(63.7%)。入组12个月后采集血浆血样,并在随后的4年期间评估血压达7次。收缩期BPV (SBPV)和舒张期BPV (DBPV)通过几个指标确定,包括变异系数(CV%),并考虑到血压随时间的变化,测量顺序和独立于平均血压水平的公式。结果:经人口统计学、体重指数、MAPT随机分组、基线收缩压、降压药、糖尿病、心血管和非心血管合并症校正后,GDF-15升高与SBPV升高(所有指标)显著相关[校正后1-SD GDF-15升高:β (SE)= 0.07 (0.04), p<0.044,为CV%]。GDF-15水平与DBPV无关。IL-6与BPV之间未发现显著相关性,而TNFR1仅与DBPV部分相关。结论:与炎症生物标志物不同,较高的GDF-15水平与较高的SBPV相关。我们的研究结果支持年龄相关的线粒体功能障碍过程是血压不稳定的基础,表明BPV可能是衰老的潜在标志。
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Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability
Aim: Increased Blood Pressure (BP) Variability (BPV) may represent an alteration in BP physiological homeostatic patterns. Most physiopathological mechanisms underlying BPV are implicated in aging. Vascular aging is associated with chronic low-grade inflammation occurring in late life, known as "inflammaging", and the hallmark “mitochondrial dysfunction” associated to stress due to age-related disorders, which in turn might contribute to higher BPV and risk of cardiovascular disease. We aimed to determine whether plasma levels of the pleiotropic stress-related mitokine Growth/Differentiation Factor 15 (GDF-15) and two inflammatory biomarkers, Interleukin 6 (IL-6) and Tumor necrosis factor receptor 1 (TNFR-1), are associated with visit-to-visit BPV in a population of community-dwelling older adults. Methods: The study population consisted of 1,096 participants [median age 75 (72-78) years; 699 females, 63.7%] selected among community-dwelling participants aged ≥70 years from the MAPT study. Plasma blood sample was collected 12 months after enrolment and BP was assessed up to seven times over a subsequent 4-year period. Systolic BPV (SBPV) and diastolic BPV (DBPV) were determined through several indicators including the coefficient of variation (CV%) and taking into account BP change over time, the order of measurements and formulas independent of mean BP levels. Results: Higher values of GDF-15 were significantly associated with increased SBPV (all indicators) after adjustment for demographics, body mass index, MAPT randomization group, baseline systolic BP, antihypertensive drugs, diabetes mellitus, cardiovascular and non-cardiovascular comorbidities [adjusted 1-SD increase in GDF-15: β (SE)= 0.07 (0.04), p< 0.044, for CV%]. GDF-15 levels were not associated with DBPV. No significant associations were found between IL-6 and BPV, whereas TNFR1 was only partially related to DBPV. Conclusions: Unlike inflammation biomarkers, higher GDF-15 levels were associated with greater SBPV. Our findings support the age-related process of mitochondrial dysfunction underlying BP instability, suggesting that BPV might be a potential marker of aging.
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