The Association between Peripheral Blood Cells and the Frailty Syndrome in Patients with Cardiovascular Diseases

Abstract

Background: Frailty syndrome is characterized by multisystem dysregulation frequently found in older individuals or even in younger patients with chronic disabling diseases such as cardiovascular diseases. Objective: To determine whether peripheral blood cell count, and its subpopulations, red blood cell and platelets, morphology and different ratios (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and red blood distribution width-to-platelet ratio) are associated with cardiac frail patients, and through this to improve the prediction of frailty status in patients with cardiovascular diseases. Method: An observational, retrospective, cohort study enrolling 179 patients with cardiovascular disease divided into two groups: non-frail group (100 pts) and frail group (79 pts), a cohort detached from the Frail.RO study. The frailty was evaluated based on the Fried criteria; haematological markers, sociodemographic data, and variables related to cardiovascular diseases and comorbidities were also recorded. Results: Lower lymphocytes, platelet count, and neutrophil-to-lymphocyte ratio were significantly associated with a more severe frailty syndrome. Regarding red blood cells, haemoglobin concentration and red cell distribution width significantly correlated with the severity of the frailty syndrome. Receiver operating characteristic curve analysis for these markers associated with the frailty syndrome revealed an acceptable sensitivity 66 % and specificity of 65% to identify frail individuals. Malnutrition and hypercholesterolemia are relevant predictors for identifying frailty in hospitalized cardiovascular patients. Conclusion: The evaluation of peripheral blood cell composition routinely measured in clinical practice can represent a valuable, but limited indicator, to diagnose frailty syndrome and eventually, the effects of interventions in frail patients with cardiovascular diseases.

Lymphocytes as a Biomarker of Frailty Syndrome: A Scoping Review

“…In order to enhance knowledge of the cellular bases of the inflammatory state associated with frailty, four studies have explored the association between frailty and the neutrophil/lymphocyte ratio (NLR) [ 21 , 25 , 26 , 29 ], which is a more accurate marker of inflammation than the individual lymphocyte count, since it reflects the balance between two cellular markers of inflammation [ 36 ]. In a study carried out in cancer patients, the NLR was positively correlated with frailty, evaluated using the Carolina frailty index of 36 items [ 21 ].…”

“…In specific terms, they observed that an increase in NLR results in an increased risk of frailty. Another study found a higher NLR in frail patients with cardiovascular disease [ 26 ]. Although this marker of inflammation has not been studied in the general population of older adults, in a study carried out by Fernández-Garrido et al [ 32 ] in institutionalized older women, the neutrophil and lymphocyte percentages were correlated with the frailty phenotype score in opposite directions.…”

“…Frailty syndrome has also been associated with an increase in some subpopulations of T lymphocytes expressing a subtype of CCR receptors. In fact, higher concentrations of total CCR5, CCR5-CD8, and CCR5-CD45RO T cells (called “memory” lymphocytes) have been described in frail older adults than in non-frail controls [ 26 ], suggesting a significant expansion of a specific subset of T cells with a proinflammatory type 1 phenotype [ 49 ]. CC chemokine receptor 5 (CCR5) interacts with CCL3, 4, 5, and 8 chemokines, and plays an important role in the regulation of leukocyte recruitment, trafficking, and immune activation [ 50 ].…”

“…In both geriatrics research and clinical settings, the most-used definitions of frailty were developed by Fried and co-workers (physical frailty phenotype) and Rockwood and co-workers (the frailty index based on accumulative deficits). Among the studies analyzed in the review, the tools mostly used were the Fried model [10,12,13,[16][17][18]20,[23][24][25][26][27][28], which defines a phenotype that includes the presence of three or more of the following clinical criteria: Involuntary weight loss in the last year, muscle weakness, gait slow, self-reported fatigue, and low physical activity [5]. For their part, Gilmore et al [29] assessed frailty using a modified version of Fried's frailty score, using four of the five available criteria (weakness, exhaustion, walking speed, and physical activity).…”

“…CCR51 T lymphocytes have been shown to have a proinflammatory type 1 phenotype, and CCR5+ T lymphocytes can significantly contribute to several inflammatory conditions such as frailty syndrome and related adverse outcomes [23,51]. Although the identification of lymphocyte counts as a possible biomarker for a single frailty criterion may be very useful for understanding the specific mechanisms responsible for the development of frailty, few studies have evaluated the relationship between lymphocyte counts with each of the five frailty criteria on the Frail scale [13,21,24,26]. Likewise, lymphocyte percentages have been found to be significantly related to low levels of physical activity and lower muscle strength in a population of institutionalized older women [16].…”