Francesco Curcio

Phase angle as bioelectrical marker to identify elderly patients at risk of sarcopenia

Several markers have been associated with sarcopenia in the elderly, including bioelectrical indices. Phase angle (PhA) is an impedance parameter and it has been suggested as an indicator of cellular death. Thus, the relationship between PhA and muscle mass and strength was investigated in 207 consecutively elderly participants (mean age 76.2±6.7years) admitted for multidimensional geriatric evaluation. Muscle strength by grip strength using a hand-held dynamometer and muscle mass was measured by bioimpedentiometer. PhA was calculated directly with its arctangent (resistance/reactance×180°/π). Linear relationship among muscular mass and strength and with clinical and biochemical parameters, including PhA at uni- and multivariate analysis were performed. Linear regression analysis demonstrated that lower level of PhA is associated with reduction in grip strength (y=3.16+0.08x; r=0.49; p<0.001), and even more, with muscle mass (y=3.04+0.25x; r=0.60; p<0001). Multivariate analysis confirms these relationships (grip strength β=0.245, p=0.031; muscular mass β=0.623, p<0.01). Thus, PhA is inversely related to muscle mass and strength in elderly subjects and it may be considered a good bioelectrical marker to identify elderly patients at risk of sarcopenia.

The defence against free radicals protects endothelial cells from hyperglycaemia-induced plasminogen activator inhibitor 1 over-production

It has been shown that hyperglycaemia may stimulate plasminogen activator inhibitor 1 (PAI-1) over-production in human endothelial cells in culture. At the same time, it has been shown that glucose may enolize, producing free radicals. In this study, the possibility that hyperglycaemia stimulates PAI-1 over-production in human endothelial cells in culture by generating free radicals has been evaluated. For this purpose two experimental models were used: human endothelial cells transfected to express high glutathione peroxidase levels cultured in hyperglycaemic media, and human endothelial cells cultured in hyperglycaemic media with the antioxidant GSH. Cells grown in 20 mM glucose produced higher values of PAI-1 with respect to controls. The production of PAI-1 was not influenced by hyperglycaemia in transfected cells. GSH in the medium reduced hyperglycaemia-induced PAI-1 over-production, but also reduces the basal production of PAI-1 in the cells grown in normal glucose concentration. These data show that antioxidant defences may reduce hyperglycaemia-induced PAI-1 over-production in human endothelial cells in culture. The hypothesis that oxidative stress may play an important role in the pathogenesis of diabetic complications is then supported by this study.

Depressed antithrombin III biological activity in opiate addicts.

Antithrombin III activity was significantly decreased in opiate addicts, but no difference was found between addict and control groups in antithrombin III plasma concentration. Moreover, glycosylated haemoglobin concentration was increased in opiate addicts, but no correlation between glycosylated haemoglobin and antithrombin III activity was found. These data show that in opiate addicts there is depressed biological activity of antithrombin III. Further characterisation of the molecular changes in antithrombin III in addicts is needed to establish whether the impaired activity is affected by altered glucose metabolism.

Oxidative stress, aging, and diseases

Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest.

Butyryl-cholinesterase is related to muscle mass and strength. A new biomarker to identify elderly subjects at risk of sarcopenia

AIMS To determine the relationship between Butyryl-cholinesterase (α-glycoprotein synthesized in the liver, b-CHE) and muscle mass and strength. METHODS Muscle mass by bioimpedentiometer and muscle strength by grip strength were evaluated in 337 elderly subjects (mean age: 76.2 ± 6.7 years) admitted to comprehensive geriatric assessment. RESULTS b-CHE levels were lower in sarcopenic than in nonsarcopenic elderly subjects (p < 0.01). Linear regression analysis demonstrated that b-CHE is linearly related with grip strength and muscular mass both in men and women (r = 0.45 and r = 0.33, p < 0.01; r = 0.55 and r = 0.39, p < 0.01; respectively). Multivariate analysis confirms this analysis. CONCLUSIONS b-CHE is related to muscle mass and strength in elderly subjects. Thus, b-CHE may be considered to be a fair biomarker for identifying elderly subjects at risk of sarcopenia.

Increased alpha-2-macroglobulin in opiate addicts: further evidence of an alteration in the coagulation system due to opiate addiction.

Antonio Ceriello, Patrizia Dello Russo, Francesco Curcio, Nicola Passariello, Dario Giugliano, Istituto di Patologia Medica, I Facoltà di Medicina, Università di Napoli, Piazza Miraglia, I-80138 Napoli (Italy) References Fuller, J.H.; Keen, H.; Jarrett, R.J.: Hemostatic variables associated with diabetes and its complications. Br. med. J. ii’.· 964–966(1979). Ceriello, A.; Giugliano, D.; Dello Russo, P.; Sgambato, S.; D’Onofrio, F.: Increased glycosylated haemoglobin A, in opiate addicts: evidence for hyperglycaemic effect of morphine. Diabetologia 22: 379(1982). Ceriello, A.; Dello Russo, P.; Curcio, F.; Rossano, P.: Increased glycosylated protein in opiate addicts. Diabetes Care 7:104–105 (1984). Increased plasma levels of α2-macroglobulin, a 4 natural linhibitor of blood coagulation, have been reported in diabetes [1]. We have previously reported that opiate addicts behave similarly to diabetics [2–4]. Therefore, we measured blood glucose, Hb Ai and o1⁄85 macroglobulin in 20 male addicts (mean age ± SD 23 ± 3.4 years) and in 20 healthy male controls (age 23 ± 2.5 years). Hb Aj and o7⁄8-macroglobulin were found to be significantly increased in addicts (Hb A] 7.2 ± 0.14%; < 7⁄8-macroglobulin 243.26 ± 62.2 mg/dl) 7 versus controls (Hb Ai 6.3 ± 0.17 %, p < 0.001; c3⁄87⁄8-mac-roglobulin 156.91 ± 37.32 mg/dl, p < 0.001). No correlation was found between Hb Ai and o1⁄8-macroglobu-lin levels. Our data demonstrate increased o7⁄8-macroglobulin levels in opiate addicts and confirm the 9 occurrence of an impairment of the blood clotting mechanism in the same addicts [5–7], in analogy to that found in diabetics [8–10]. Passariello, N.; Giugliano, D.; Quatraro, A.; Consoli, G.; Sgambato, S.; Torella, R.; D’Onofrio, F.: Glucose tolerance and hormonal responses in heroin addicts. A possible role for endogenous opiates in the pathogenesis of non-insulin dependent diabetes. Metabolism 32: 1163–1165 (1983). Passariello, N.; Giugliano, D.; Ceriello, A.; Misso, L.; Quatraro, A.: Increased platelet aggregation in opiate addicts. Blood 60: 276(1982). Ceriello, A.; Dello Russo, P.; Niola, O.; Schimizzi, S.; Capez-zuto, C: Fibrinogen levels in opiate addicts. Thromb. Haemos-tasis 50: 759(1983).

Impact of SPRINT results on hypertension guidelines: implications for “frail” elderly patients

In the last years, guidelines for the treatment of hypertension recommended individualized blood pressure goals for geriatric population because of elderly susceptibility to adverse outcomes and higher mortality rate deriving from the excessive blood pressure lowering, especially in “frail” elderly. Recent findings from the SPRINT study, which demonstrated that intensive blood pressure lowering was associated with lower rates of cardiovascular events and mortality in both hypertensive fit and frail elderly subjects compared to standard treatment, heavily influenced the recent US guidelines. In SPRINT sub-study analysis of adults aged ≥75 years, the most controversial issue appears the method of blood pressure measurement, the selection of patients and related-frailty degree that appears to be very light. Accordingly, it has been described that light frailty is related to good outcomes in older adults. SPRINT findings in “frail elderly patients” cannot be applied to the clinical practice because this condition has been clearly under-estimated. Thus, frailty status should be routinely and correctly quantified in order to identify the frailty degree and to find the best harms–benefits balance of antihypertensive drug treatment in frail older adults.

The reverse metabolic syndrome in the elderly: Is it a “catabolic” syndrome?

Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure are also found to relate to outcomes in the geriatric population, but in a differing direction. A higher body mass index, hypercholesterolemia and hypertension are not harmful but even permit better survival at advancing age. This phenomenon is called “reverse epidemiology” or “risk factor paradox” and is also detected in a variety of chronic disease states such as chronic heart failure. Accordingly, a low BMI, blood pressure and cholesterol values are associated with a worse prognosis. Several possible causes are hypothesized to explain this elderly paradox, but this phenomenon remains controversial and its underlying reasons are poorly understood. The aim of this review is to recognize the factors behind this intriguing phenomenon and analyse the consequences that it can bring in the management of the cardiovascular therapy in elderly patient. Finally, a new phenotype identified as “catabolic syndrome” has been postulated.

Risk of Malnutrition Evaluated by Mini Nutritional Assessment and Sarcopenia in Noninstitutionalized Elderly People

BACKGROUND Malnutrition indices and muscle mass and strength in the elderly are poorly investigated. Moreover, malnutrition seems to be 1 of the more important factors in the cause of sarcopenia. The presence of sarcopenia and its relationship with malnutrition indices were studied in noninstitutionalized elderly people who underwent Comprehensive Geriatric Assessment (CGA). METHODS A total of 473 elderly subjects (mean age, 80.9 ± 6.6 years) admitted to CGA were studied. Malnutrition risk was evaluated with Mini Nutritional Assessment (MNA) score, whereas muscle mass and muscle strength were evaluated by bioimpedentiometry and hand grip, respectively. Sarcopenia was assessed as indicated in the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. RESULTS Overall prevalence of sarcopenia was 13.1%, and it increased from 6.1% to 31.4% as MNA decreased (P < .001). MNA score was lower in elderly subjects with sarcopenia (15.4 ± 4.2) than without sarcopenia (22.0 ± 4.0) (P = .024). Linear regression analysis showed that MNA score is linearly related both with muscle mass (r = 0.72; P < .001) and strength (r = 0.42; P < .001). Multivariate analysis, adjusted for several confounding variables including comorbidity and disability, confirmed these results. CONCLUSIONS MNA score is low in noninstitutionalized elderly subjects with sarcopenia, and it is linearly related to muscle mass and muscle strength. These data indicate that MNA score, when evaluated with muscle mass and strength, may recognize elderly subjects with sarcopenia.

Hypotensive Drugs and Syncope Due to Orthostatic Hypotension in Older Adults with Dementia (Syncope and Dementia Study)

To determine whether hypotensive drugs may play a pivotal role in inducing orthostatic hypotension (OH)‐related syncope.