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Alessandro Ble

Publications and source records attributed to Alessandro Ble.

15 recordsLinked to original sources
PubMed2007

Hypercortisolemic depression is associated with the metabolic syndrome in late-life.

INTRODUCTION: Depression has been hypothesized to be associated with metabolic abnormalities which increase the risk of cardiovascular disease (CVD) and diabetes. Such a link could be due to increased HPA-axis activity. This study investigates the cross-sectional relationship between depression, urinary cortisol and metabolic syndrome in an older population. METHODS: Data are from 867 participants of the InChianti Study, aged 65 years. Depressive symptoms were assessed using the CES-D scale; cortisol levels were determined in 24-h urine samples. Metabolic syndrome was defined as three or more of the following: abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure, and high fasting glucose. RESULTS: Clinically relevant depressed mood (CES-D20) was present in 20.6% of the sample, and 24.5% had the metabolic syndrome. After adjustment for sociodemographics and health indicators, depression score (per SD increase: OR=1.20, 95% CI=1.02-1.41) and urinary cortisol level (per SD increase: OR=1.23, 95% CI=1.01-1.51) were significantly associated with presence of metabolic syndrome. There was, however, a significant interaction (p=0.003) between depressed mood and urinary cortisol in the probability of having metabolic syndrome. The odds of metabolic syndrome in persons with both depressed mood and urinary cortisol excretion in the highest tertile was 1.84 (95% CI=1.02-3.34) compared to persons with neither condition. DISCUSSION: This study suggests a synergistic relationship between depression, cortisol and metabolic syndrome. Hypercortisolemic depression may constitute a specific risk group for the metabolic syndrome.

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PubMed2006

Sarcopenic obesity and inflammation in the InCHIANTI study.

The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as "sarcopenic obesity" (Roubenoff R. Ann NY Acad Sci 904: 553-557, 2000). Research suggests that inflammatory cytokines produced by adipose tissue, especially visceral fat, accelerate muscle catabolism and thus contribute to the vicious cycle that initiates and sustains sarcopenic obesity. We tested the hypothesis that obesity and poor muscle strength, hallmarks of sarcopenic obesity, are associated with high circulating levels of proinflammatory cytokines in a random sample of the residents of two municipalities in the Chianti geographic area (Tuscany, Italy). The study sample consisted of 378 men and 493 women 65 yr and older with complete data on anthropometrics, handgrip strength, and inflammatory markers. Participants were cross-classified according to sex-specific tertiles of waist circumference and grip strength and according to a cut point for obesity of body mass index > or =30 kg/m(2). After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated levels of IL-6, C-reactive protein, IL-1 receptor antagonist, and soluble IL-6 receptor (P < 0.05). Our findings suggest that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity. These results suggest that proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity.

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PubMed2006

Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study.

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.

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PubMed2006

Low testosterone levels and the risk of anemia in older men and women.

BACKGROUND: Anemia is a frequent feature of male hypogonadism and anti-androgenic treatment. We hypothesized that the presence of low testosterone levels in older persons is a risk factor for anemia. METHODS: Testosterone and hemoglobin levels were measured in a representative sample of 905 persons 65 years or older without cancer, renal insufficiency, or anti-androgenic treatments. Hemoglobin levels were reassessed after 3 years. RESULTS: At baseline, 31 men and 57 women had anemia. Adjusting for confounders, we found that total and bioavailable testosterone levels were associated with hemoglobin levels in women (P = .001 and P = .02, respectively) and in men (P<.001 and P = .03, respectively). Men and women in the lowest quartile of total and bioavailable testosterone were more likely than those in the highest to have anemia (men, 14/99 vs 3/100; odds ratio [OR], 5.4; 95% confidence interval [CI], 1.4-21.8 for total and 16/99 vs 1/99; OR, 13.1; 95% CI, 1.5-116.9 for bioavailable testosterone; women, 21/129 vs 12/127; OR, 2.1; 95% CI, 0.9-5.0 for total and 24/127 vs 6/127; OR, 3.4; 95% CI, 1.2-9.4 for bioavailable testosterone). Among nonanemic participants and independent of confounders, men and women with low vs normal total and bioavailable testosterone levels had a significantly higher risk of developing anemia at 3-year follow-up (21/167 vs 28/444; relative risk, 2.1; 95% CI, 1.1-4.1 for total and 26/143 vs 23/468; relative risk, 3.9; 95% CI, 1.9-7.8 for bioavailable testosterone). CONCLUSION: Older men and women with low testosterone levels have a higher risk of anemia.

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PubMed2006

Circulating inflammatory cytokine expression in men with prostate cancer undergoing androgen deprivation therapy.

Prostate cancer (PCa) is one of the most common cancers in men. Androgen deprivation therapy (ADT) is employed in the treatment of patients with metastatic or recurrent PCa, resulting in castrate levels of testosterone. Recent studies have shown that male hypogonadism is associated with increased levels of proinflammatory and diminished concentrations of anti-inflammatory cytokines, which normalize upon testosterone treatment. Furthermore, an inflammatory state is associated with osteoporosis, sarcopenia and metabolic abnormalities. We examined 3 groups of men: 1) 20 men with PCa undergoing ADT for at least 12 months prior to the onset of the study (ADT group); 2) 18 age-matched men with non-metastatic PCa who had undergone local surgery and/or radiotherapy and had not yet received ADT and were eugonadal (non-ADT group); and 3) 20 age-matched healthy eugonadal men (control group). None of the subjects were suffering from any acute or chronic inflammatory conditions. Mean age was similar in the 3 groups (P = .41). Men in the ADT and non-ADT groups had higher BMI compared to the control group (P = .0005 and P = .01, respectively). Men in the ADT group had significantly lower mean serum total (P < .0001) and free (P < .0001) testosterone and estradiol (P < .0001) levels compared to the other 2 groups. No significant differences in serum levels of pro-inflammatory or anti-inflammatory cytokines were observed between the 3 groups. These data suggest that men with PCa undergoing long-term ADT do not have elevated levels of pro-inflammatory cytokines compared to age and disease matched controls. Prospective studies are needed to evaluate for any acute changes in these inflammatory markers that might occur after the initiation of ADT.

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PubMed2006

Uric acid and inflammatory markers.

AIMS: The role of uric acid (UA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that UA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. METHODS AND RESULTS: We evaluate a relationship between UA levels and several inflammatory markers in 957 subjects, free of severe renal failure, from a representative Italian cohort of persons aged 65-95. Plasma levels of UA and white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6r), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-alpha) were measured. Complete information on potential confounders was collected using standard methods. WBC (P=0.0001), neutrophils (P<0.0001), C-reactive protein (P<0.0001), IL-1ra (P<0.0001), IL-6 (P=0.0004), sIL-6r (P=0.002), IL-18 (P<0.0001), TNF-alpha (P=0.0008), and the percentage of subjects with abnormally high levels of C-reactive protein (P=0.004) and IL-6 (P=<0.0001) were significantly higher across UA quintiles. After adjustment for age, sex, behaviour- and disease-related confounders, results were virtually unchanged. In subjects with UA within the normal range, UA was significantly and independently associated with neutrophils count, C-reactive protein, IL-6, IL-1ra, IL-18, and TNF-alpha, whereas non-significant trends were observed for WBC (P=0.1) and sIL-6r (P=0.2). CONCLUSION: A positive and significant association between UA and several inflammatory markers was found in a large population-based sample of older persons and in a sub-sample of participants with normal UA. Accordingly, the prevalence of abnormally high levels of C-reactive protein and IL-6 increased significantly across UA quintiles.

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PubMed2006

Association of executive function and performance of dual-task physical tests among older adults: analyses from the InChianti study.

BACKGROUND: previous studies have reported an association between cognitive function and physical performance, particularly among older adults. OBJECTIVE: to examine the association between executive function and performance difference on complex versus usual walking tasks in a sample of non-demented older adults. DESIGN: population-based epidemiological study of older people residing in the Chianti area (Tuscany, Italy). PARTICIPANTS: 737 community-dwelling individuals aged 65 years and older. METHODS: gait speed (m/s) was measured during the performance of complex walking tasks (walking/talking, walking/picking-up an object, walking/carrying a large package, walking over obstacles, walking with a weighted vest) and reference walking tasks (7 m usual pace, 7 m fast pace and 60 m fast pace). Executive function was assessed using the Trail Making Test (TMT). Other measures included Mini-Mental State Examination (MMSE), sociodemographic characteristics and selected physiological impairments. RESULTS: gait speed for the selected reference and complex walk tasks was consistently lower among participants with poor executive function. Per cent decline in gait speed compared with the reference task differed by executive function for certain tasks (e.g. walking/obstacles: 30 versus 24% decline in low versus high executive function respectively, P = 0.0006) but not for others. CONCLUSIONS: poor executive function is associated with measures of gait, including specific challenges. Overall, the results showed that the cost associated with the addition of a challenge to the basic walking task differs by executive function and the nature of the task. Further research is needed to determine whether improvement in executive function abilities translates to better performance on selected complex walking tasks.

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PubMed2006

Lower plasma vitamin E levels are associated with the frailty syndrome: the InCHIANTI study.

BACKGROUND: The primary biologic mechanism that causes frailty in older persons has never been adequately explained. According to recent views, oxidative stress may be the driving force of this condition. We tested the hypothesis that, independent of confounders, low plasma levels of vitamin E (alpha-tocopherol), the main fat-soluble human antioxidant, are associated with the frailty syndrome in older persons free from dementia and disability. METHODS: The study sample included 827 older (> or =65 years) persons (women, 54%) who participated in a population-based epidemiological study. Frail participants were identified based on the presence of at least three of five of the following features: self-reported weight loss, low energy, slow gait speed, low grip strength, and low physical activity. Participants with none of these features were considered nonfrail, while participants with one or two were considered intermediate frail. Plasma vitamin E levels were determined using reverse-phase high-performance liquid chromatography. Measured confounders included lower extremity muscle strength, cognitive function, diseases, and factors related to vitamin E metabolism. RESULTS: Age- and gender-adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend =.015). In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertile were less likely to be frail than were participants in the lowest vitamin E tertile (odds ratio, 0.30; 95% confidence interval, 0.10-0.91). CONCLUSIONS: Our findings show an association between low circulating levels of one of the most important components of the human antioxidant system and the presence of frailty.

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PubMed2006

Association between hormones and metabolic syndrome in older Italian men.

OBJECTIVES: To determine whether low levels of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAS) and high levels of cortisol and leptin would be associated with metabolic syndrome (MS). DESIGN: Cross-sectional. SETTING: Population-based sample of older Italian men. PARTICIPANTS: Four hundred fifty-two men aged 65 and older enrolled in the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS: Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and leptin. MS was defined according to Adult Treatment Panel III criteria. RESULTS: MS was present in 73 men (15.8% of the sample). After adjusting for confounders, total testosterone (P < .05) and log (SHBG) (P < .001) were inversely associated, whereas log (leptin) was positively associated with MS (P < .001). Independent of age, log (SHBG) was positively associated with high-density lipoprotein cholesterol (P < .05) and negatively associated with abdominal obesity (P < .001) and triglycerides (P < .001). Log (leptin) was significantly associated with each component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-1 were not associated with MS. Having three or more hormones in the lower (for hormones lower in MS) or the upper (for hormones higher in MS) quartile was associated with three times the risk of being affected by MS (odds ratio = 2.8, 95% confidence interval = 1.3-6.9) (P = .005), compared with not having this condition. CONCLUSION: Total testosterone and SHBG are negatively and leptin is positively associated with MS in older men. Whether specific patterns of hormonal dysregulation predict the development of MS should be tested in longitudinal studies.

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PubMed2005

Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men.

CONTEXT: An age-associated decline in testosterone (T) levels and an increase in proinflammatory cytokines contribute to chronic diseases in older men. Whether and how these changes are related is unclear. OBJECTIVE: We hypothesized that T and inflammatory markers are negatively correlated in older men. DESIGN: This was a cross-sectional study. SETTING: A population-based sample of older men was studied. PARTICIPANTS AND MEASURES: After excluding participants taking glucocorticoids or antibiotics or those with recent hospitalization, 467 men, aged 65 yr or older, had complete determinations of total T, bioavailable T, SHBG, albumin, IL-6, soluble IL-6 receptor (sIL-6r), TNF-alpha, IL-1beta, and C-reactive protein. RESULTS: After adjusting for potential confounders, sIL-6r was significantly and inversely correlated with total T (r = -0.20; P < 0.001) and bioavailable T (r = -0.12; P < 0.05). T was not correlated with any other inflammatory marker. CONCLUSIONS: These preliminary findings suggest an inverse relationship between T and sIL-6r. Longitudinal studies are needed to establish the causality of this association.

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PubMed2005

Renal function, erythropoietin, and anemia of older persons: the InCHIANTI study.

BACKGROUND: In the older population, anemia has been associated with poor outcomes including disability and mortality. Understanding the mechanisms leading to anemia is essential to plan better treatment and prevention strategies. We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythropoietin levels. METHODS: Data were from the InCHIANTI study, a population-based study performed in a sample of community-dwelling older (> or = 65 years) persons living in Italy. This analysis included 1005 participants with complete data on hemoglobin and erythropoietin levels and markers of renal function. RESULTS: The prevalence of anemia according to the World Health Organization criteria (hemoglobin level < 12 g/dL for women and < 13 g/dL for men) was 12.0% and increased with age in both sexes. After adjusting for age, diseases, and other confounders, only participants with a creatinine clearance (CrCl) of 30 mL/min or lower (< or = 0.50 mL/s) had a higher prevalence of anemia compared with those with a CrCl higher than 90 mL/min (> 1.50 mL/s) (P<.01). Consistently, participants with a CrCl of 30 mL/min or lower (< or = 0.50 mL/s) had significantly lower age- and hemoglobin-adjusted erythropoietin endogenous levels. After excluding men and women with CrCl of 30 mL/min or lower (< or = 0.50 mL/s) and adjusting for confounders, we found a trend toward an increase in prevalence of anemia with decreasing renal function; however, it was not statistically significant. CONCLUSIONS: Severe age-related decline in renal function is associated with a reduced erythropoietin secretion and anemia. Whether moderate kidney impairment in older persons is associated with a progressively increasing risk of anemia remains to be determined.

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PubMed2005

Relation of plasma leptin to C-reactive protein in older adults (from the Invecchiare nel Chianti study).

Obese subjects have higher circulating levels of C-reactive protein (CRP) than normal subjects, and it has been shown that CRP per se may contribute to atherogenesis. The mechanism linking increased fat mass with high CRP levels has not been exhaustively explained. It has been suggested that adipose tissue-produced cytokines, including interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta, represent the causal link between increased body fat and high CRP levels. It has been hypothesized that the hormone leptin, released by fat cells, may stimulate CRP production independent of cytokines. This study measured circulating leptin, CRP, interleukin-6, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 in 946 community-dwelling older subjects (398 men, 548 women; age range 65 to 102 years) enrolled in a large population-based study. Confounders included demographics, functional, cognitive and affective status, diet and lifestyle, body composition, drugs, and chronic diseases. A direct association was found between leptin and CRP (p = 0.004), independent of cytokines and other possible confounders. The association was stronger in younger than in older subjects but was not influenced by gender or body mass index. In conclusion, these findings suggest that leptin may directly stimulate the production of CRP independent of fat-cell produced cytokines in older adults.

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PubMed2004

A flame burning within.

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response is a plastic network composed of redundant signaling among several different mediators. These mediators have a reciprocal relationship with other biological sub-systems, including hormone regulation, the autonomic nervous system, and oxidative/anti-oxidant balance. Studying this complex architecture requires parallel and multiple research strategies from epidemiological to biochemical level, from observational studies to innovative intervention approaches. Given that the inflammatory response is a critical age-related process, understanding its regulatory action is essential in avoiding hazardous consequences in old age.

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PubMed2004

Prescription of anti-oedema agents and short-term mortality in older patients with acute ischaemic stroke.

BACKGROUND AND OBJECTIVE: In Western countries, stroke is the third most common cause of death and one of the main causes of disability in individuals aged over 65 years. Mortality at 1 month after stroke is still high, at around 25-30%. Despite the widespread use of anti-oedema agents in clinical practice, there are only a few studies that have investigated the effect of these drugs on stroke outcome. In this study we evaluated the effect of intravenously administered glycerol or mannitol individually and in combination with corticosteroids, on short-term mortality (30 days). The sample included patients aged over 65 years who were admitted to hospital for acute ischaemic stroke. STUDY DESIGN: This was a retrospective cohort study. The odds ratio, estimated by means of multivariate logistic regression method, was used to compare short-term mortality risk across treatment groups after adjusting for possible confounders. METHODS: This study included 442 consecutive patients aged over 65 years with severe ischaemic stroke who were admitted to either the University School of Internal Medicine (Ferrara) or the Geriatric Department (Perugia), Italy, over a 4-year period (1996-2000). All patients underwent a computed tomography (CT) scan of the brain within 72 hours of admission. Stroke type was classified according to the system used by the Oxfordshire Community Stroke Project. The data recorded included: (i) clinical features of stroke; (ii) detailed medical history, including vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, coronary heart disease, congestive heart failure, alcohol abuse, smoking, previous transient ischaemic attacks or stroke); (iii) 12-lead ECG; and (iv) routine blood analysis and urine tests. RESULTS: No reduction in short-term mortality risk was observed in patients treated with intravenous (IV) glycerol. However, an increase in short-term mortality risk was observed in the patients who were concurrently treated with IV corticosteroids. Similarly, treatment with mannitol did not reduce the risk of short-term mortality; however, concurrent treatment with IV corticosteroids did not show a significant rise in short-term mortality risk. When treatment with IV glycerol and mannitol was considered together, the treatment did not decrease short-term mortality risk, while concurrent therapy with corticosteroids was associated with an increase in short-term mortality risk. CONCLUSION: This study does not support the use of IV osmotic agents such as glycerol or mannitol in the prevention of short-term mortality in older patients with acute ischaemic stroke. Furthermore, our data suggest a possible harmful effect of IV corticosteroids on short-term mortality risk.

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