Association between endothelial dysfunction and frailty: the Toledo Study for Healthy Aging

Abstract

Cardiovascular disease (CVD), both clinical and subclinical, has been proposed as one of the mechanisms underlying frailty. However, there is no evidence addressing the relationship between the earliest stage of CVD (endothelial dysfunction) and frailty. The goal of the study was to analyze the association between endothelial dysfunction, evaluated by asymmetric dimethylarginine (ADMA) levels, and frailty. We used data from the Toledo Study for Healthy Aging, a prospective Spanish cohort study. Biological samples were obtained and ADMA levels were determined using an enzyme immunoassay method. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals of frailty associated with ADMA. Adjustments were made for age, gender, cardiovascular risk factors, and presence of atherosclerotic disease (assessed by ankle–brachial index; ABI). One thousand two hundred eighty-seven community-dwelling elderly were included. One hundred seven (8.3 %) were identified as frail, 542 (42.1 %) as pre-frail, and 638 (49.6 %) as non-frail. ADMAvalues were higher in frail subjects than in non-frail ones. In addition, an interaction between the presence of atherosclerotic disease and ADMA on the odds of frailty (p=0.045) was detected. After adjustments for age, classical cardiovascular risk factors, and ABI, the risk of frailty was associated with increasing levels of ADMA in subjects without atherosclerotic disease [OR for 1 standard deviation increase in ADMA=1.14 (1.01–1.28), p=0.032] but not in those with atherosclerotic disease. In our study, endothelial dysfunction, assessed by ADMA levels, is associated with frailty. These findings provide additional support for a relevant role of vascular system since its earliest stage in frailty.

Mediterranean Diet and Risk of Frailty in Community-Dwelling Older Adults

“…In fact, there is evidence that frailty is associated with subclinical cardiovascular disease. 34,35 Third, although 2 different instruments were used to assess MD, they yielded quite consistent results on the association between MD and frailty. This increases the confidence in the observed association between MD and frailty.…”

Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults

“…In this sense, the risk of frailty in older adults without atherosclerotic disease increased as the levels of asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction, increased (Alonso-Bouzón et al, 2014). In fact, the impairment of endothelial vasodilation induced by insulin in older adults relates to the defective anabolism of muscle proteins driven by this hormone in skeletal muscle (Timmerman and Volpi, 2013).…”

“…1) (Fried et al, 2001;Laosa et al, 2014;Rodríguez-Mañas and Fried, 2015). This high vulnerability is due to changes in several physiologic systems, mainly inflammation, insulin-resistance, alterations in coagulation systems, endothelial and vascular dysfunction (Alonso-Bouzón et al, 2014;Barzilay et al, 2007;Leng et al, 2007). These changes lead to the so-called "cycle of Frailty" (Walston et al, 2006), which finally produces sarcopenia, that is the target organ explaining many of the clinical manifestations of the syndrome (Fig.…”

Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease

“…38e40 Additional biomarkers have recently been identified for roles in frailty, such as those related to endothelial dysfunction or micro RNAs central to the aging process. 41,42 Frailty can be defined as an age-associated biological syndrome characterized by a decreased biological reserve resulting from a decline in multiple physiological systems that leaves the individual at risk for developing poor outcomes (disability, death, and hospitalization) in the presence of stressors. 43,44 The prevalence of frailty in people older than 65 is approximately 10%, increases with age, and is greater in women.…”