Nicola Veronese

Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies

To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs).

Inflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

Pre-frailty and risk of cardiovascular disease in elderly men and women: the Pro.V.A. study.

BACKGROUND Frailty is an important risk factor for cardiovascular disease (CVD), but the impact of early, potentially reversible stages of frailty on CVD risk is unknown. OBJECTIVES This study sought to ascertain whether pre-frailty can predict the onset of CVD in a cohort of community-dwelling, not disabled, elderly people. METHODS A sample of 1,567 participants age 65 to 96 years without frailty or disability at baseline was followed for 4.4 years. Pre-frailty was defined as the presence of 1 or 2 modified Fried criteria (unintentional weight loss, low physical activity level, weakness, exhaustion, and slow gait speed), and incident CVD as onset of coronary artery diseases, heart failure, stroke, peripheral artery disease, or CVD-related mortality. RESULTS During follow-up, 551 participants developed CVD. Compared with participants who did not become frail, those with 1 modified Fried criterion (p = 0.03) and those with 2 criteria (p = 0.001) had a significantly higher risk of CVD, even after adjusting for several potential confounders (traditional risk factors for CVD, inflammatory markers, and hemoglobin A1c levels). Low energy expenditure (p = 0.03), exhaustion (p = 0.01), and slow gait speed (p = 0.03) were significantly associated with the onset of CVD, whereas unintentional weight loss and weakness were not. CONCLUSIONS Our findings suggest that pre-frailty, which is potentially reversible, is independently associated with a higher risk of older adults developing CVD. Among the physical domains of pre-frailty, low gait speed seems to be the best predictor of future CVD.

Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression.

OBJECTIVE Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCTs) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCTs. METHOD Three authors identified RCTs from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. RESULTS Overall, 40 RCTs were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (β=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (β=-1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (β=-1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). CONCLUSIONS Exercise is well tolerated by people with depression and drop out in RCTs is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription.

What are the roles of calorie restriction and diet quality in promoting healthy longevity

Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan. Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes the expected age-associated alterations in myocardial stiffness, autonomic function, and gene expression in the human skeletal muscle. However, it is possible that some of the beneficial effects on metabolic health are not entirely due to CR, but to the high quality diets consumed by the CR practitioners, as suggested by data collected in individuals consuming strict vegan diets. More studies are needed to understand the interactions among single nutrient modifications (e.g. protein/aminoacid, fatty acids, vitamins, phytochemicals, and minerals), the degree of CR and the frequency of food consumption in modulating anti-aging metabolic and molecular pathways, and in the prevention of age-associated diseases.

ReviewInflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

Inflammatory cytokines and anorexia nervosa: A meta-analysis of cross-sectional and longitudinal studies

OBJECTIVE Although inflammation is increasingly implicated in psychiatric disorders, less is known about its role in anorexia nervosa (AN), an illness with low body mass index (BMI). METHODS We performed a systematic PubMed literature search until 12/31/2013 and meta-analyzed cross-sectional and longitudinal studies comparing circulating pro- and anti-inflammatory cytokines between patients with anorexia nervosa (AN) and healthy controls (HCs) (1) before and (2) after weight gain, and (3) within AN patients before and after weight gain. Standardized mean differences (SMDs)± 95% confidence intervals (CIs) for results from ≥ 2 studies were calculated. RESULTS Of 999 initial hits, 22 studies with 924 participants (AN=512, HCs=412) were eligible. Compared to HCs, tumor necrosis factor (TNF)-alpha (SMD=0.35, 95%CI=0.09-0.61, p=0.008), interleukin (IL)1-beta (SMD=0.51, 95%CI=0.18-0.84, p=0.003), IL-6 (SMD=0.43, 95%CI=0.11-0.76, p=0.009), and TNF-receptor-II (SMD=0.42, 95%CI:0.07-0.78, p=0.02) were significantly elevated in AN, while C-reactive protein (SMD=-0.53, 95%CI=-.77, -0.28, p<0.0001) and IL-6 receptor (SMD=-0.85, 95%CI=-1.33, -0.36, p=0.0006) were significantly decreased. No differences were found for TNF-receptor I and TGF-β. Across a subset of eight longitudinal studies (AN=152, HCs=129), significant weight gain (baseline BMI=15.4 ± 1.5, endpoint BMI=18.2 ± 1.6, p<0.0001) was not associated with significant changes in TNF-α, IL-6 and IL1-β. However, after weight gain, IL-6 was not different anymore compared to HCs (SMD=0.06, 95%CI=-0.32, 0.45, p=0.75). In meta-regression, shorter illness duration (p=0.0008), but not younger age (p=0.71) significantly moderated greater IL-6 levels. CONCLUSION Despite abnormally low BMI, AN seems to be associated with increased inflammatory cytokines. Whether specific elevated cytokines represent trait or state markers of AN, and whether they could be treatment targets requires further study.

Inverse relationship between body mass index and mortality in older nursing home residents: A meta-analysis of 19,538 elderly subjects

Body mass index (BMI) and mortality in old adults from the general population have been related in a U‐shaped or J‐shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m2), the most adjusted hazard ratios (HRs) according to a pre‐defined list of covariates were obtained from authors and pooled by random‐effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow‐up were meta‐analysed. Compared with normal weight, all‐cause mortality HRs were 1.41 (95% CI = 1.26–1.58) for underweight, 0.85 (95% CI = 0.73–0.99) for overweight and 0.74 (95% CI = 0.57–0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 [95% CI = 1.13–2.40]). RR results corroborated primary HR results, with additionally lower infection‐related mortality in overweight and obese than in normal‐weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.

Three Decades of Comprehensive Geriatric Assessment: Evidence Coming From Different Healthcare Settings and Specific Clinical Conditions

Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.