An Increase in Vascular Stiffness is Positively Associated with Mitochondrial Bioenergetics Impairment of Peripheral Blood Mononuclear Cells in the Elderly Population

Abstract

The cardio-ankle vascular index (CAVI) is a non-invasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a non-invasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the elderly population. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand (EGAT) between 2017 and 2018. 1640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into three groups based on their CAVI values as high (CAVI ≥9), moderate (9 >CAVI ≥8), and low (CAVI <8), in which each group comprised 702, 507 and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.