Pinar Soysal

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.

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.

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

AIM Depression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty. METHODS Two authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders. RESULTS From 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07-47.10, I2=94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66-7.35, k=11), also after adjusting for potential confounders (OR=2.64; 95%CI: 1.59-4.37, I2=55%, k=4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00-55.30, I2=97%). People with depression were at increased odds of having frailty (OR=4.07, 95%CI 1.93-8.55, k=8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95-7.08, I2=98%, k=4), whilst in two studies frailty increased the risk of incident depression with an OR=1.90 (95%CI 1.55-2.32, I2=0%). CONCLUSION This meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.

Which cholinesterase inhibitor is the safest for the heart in elderly patients with Alzheimer's disease?

Objective: Cholinesterase inhibitors (ChEIs) are widely used for the treatment of Alzheimer’s disease (AD); however, their cholinergic side effects on the cardiovascular system are still unclear. In this study, we aimed to examine the side effects caused by donepezil, rivastigmine, and galantamine on cardiac rhythm and postural blood pressure changes in elderly patients with AD. Methods: Of 204 consecutive elderly patients who were newly diagnosed with AD, 162 were enrolled and underwent comprehensive geriatric assessments. The electrocardiographs (ECGs) and blood pressures were recorded at the baseline and 4 weeks after the dose of 10 mg/d of donepezil, 10 cm2/d of rivastigmine, and 24 mg/d of galantamine. Results: There were no changes relative to the baseline in any of the ECG parameters or arterial blood pressure with any of the administered ChEIs. Conclusion: It was demonstrated that none of the 3 ChEIs were associated with increased negative chronotropic, arrhythmogenic, and hypotensive effects for the elderly patients with AD.

The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer’s disease

AIMS The present study aimed to evaluate effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4I), on cognitive functions in elderly diabetic patients with and without cognitive impairment. METHODS 253 elderly patients with type 2DM, were enrolled in this prospective and observational study. After comprehensive geriatric assessment, the patients were divided into either sitagliptin or non-sitagliptin group. RESULTS A total of 205 patients who completed the study (52 with Alzheimers Disease (AD)) were re-evaluated 6months later. Sixth-month evaluation revealed no difference between sitagliptin and non-sitagliptin groups in terms of weight, body mass index, and HbA1c (p>0.05). However, the number of patients that required reduced insulin dose was significantly higher in the sitagliptin group (p=0.01). Sitagliptin therapy was associated with an increase in the Mini-Mental State Examination (MMSE) scores (p=0.034); patients without AD receiving only sitagliptin or insulin showed higher MMSE scores as compared to the patients receiving metformin alone (p=0.024). Likewise, the change in MMSE scores in AD patients receiving sitagliptin was significant and indicated improvement as compared to the patients receiving metformin (p=0.047). CONCLUSION Besides its effects similar to those of insulin and metformin in glycemic control and in reducing need for insulin, 6-month sitagliptin therapy may also associated with improvement of cognitive function in elderly diabetic patients with and without AD. Further randomized controlled trials are needed to support these results.

Does vitamin D deficiency increase orthostatic hypotension risk in the elderly patients

Orthostatic hypotension (OH) is closely associated with falls, cardiovascular events and mortality in the elderly patients. The aim of the study is to evaluate the OH prevalence among patients over the age of 65 years, to find out the impact of this condition on daily living activities, and to determine the possible effects of vitamin D levels on OH in elderly patients. Eight hundred and forty nine geriatric patients who had undergone comprehensive geriatric assessment were retrospectively evaluated and 546 patients were included in the study. The patients demographic characteristics, blood pressures, comorbid diseases, polypharmacy status, cognitive and nutritional states, basic and instrumental daily living activity indexes and laboratory values were obtained from hospital files. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay. The prevalence of OH was found to be 27.5%. Both daily living activity indexes were significantly lower in older patients with OH (p<0.02), and serum 25(OH)D levels were significantly lower in older patients with OH (p<0.01). Our findings suggest that vitamin D deficiency may be a factor in OH development. Because this condition is also preventable and correctable, serum vitamin D levels should be checked during the evaluation of OH patients and any detected deficiency should be treated accordingly.

Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis investigating the influence of acetylcholinesterase inhibitors (AChEIs) therapy on nutritional status and weight across observational and interventional studies. Two authors searched major electronic databases from inception until 10/14/2015 for longitudinal, open-label and randomised double-blind placebo controlled (randomised controlled trials (RCTs)) studies of AChEIs in patients with dementia reporting nutritional status outcome data. Out of 3551 initial hits, 25 studies (12 open-label trials, 9 RCTs and 4 longitudinal studies) including 10 792 patients with dementia were meta-analysed. In longitudinal studies (median follow-up 6 months), a significant cumulative incidence of weight loss between baseline and follow-up evaluation was observed (studies=2; 5%; 95% CI 1% to 34%, p<0.0001; I2=95%). These findings were confirmed in open-label trials (6%; 95% CI 4% to 7%, p<0.0001; I2=78%). In 9 RCTs (median follow-up 5 months), those taking AChEIs more frequently experienced weight loss than participants taking placebo (OR=2.18; 95% CI 1.50 to 3.17, p<0.0001; I2=29%). AChEIs therapy contributes to weight loss in patients with dementia, with a 2-fold increased risk observed in the meta-analysis of RCTs. Clinicians should carefully consider the benefit and risk of prescribing AChEIs. Nutritional status should be routinely evaluated in patients with dementia treated with AChEIs.

Hypovitaminosis D and orthostatic hypotension: a systematic review and meta-analysis.

Objectives: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). Methods: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25–2.84; I2 = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13–3.68; I2 = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = −0.42; 95% CI: −0.72 to −0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. Conclusion: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.

Effect of vildagliptin add-on treatment to metformin on plasma asymmetric dimethylarginine in type 2 diabetes mellitus patients

Aims A close association has been demonstrated between increased cardiovascular risk and high asymmetric dimethylarginine (ADMA) levels in type 2 diabetes mellitus (DM) patients. We planned to measure serum ADMA levels in type 2 DM patients using vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. Materials and methods A total of 68 type 2 DM patients who were on metformin were enrolled in the study. Based on the glycemic levels of patients, vildagliptin was added on to treatment in 33 patients. Patients were followed for 6 months. Serum ADMA, C-reactive protein, and fibrinogen levels were compared in groups of patients using metformin or metformin + vildagliptin, after 6 months. Results Serum ADMA levels were found to be significantly lower in the group using vildagliptin compared to the group using metformin + vildagliptin (P<0.001). However, serum C-reactive protein and fibrinogen levels were statistically similar in the two study groups (P=0.34 and P=0.23, respectively). Conclusion Metformin + vildagliptin treatment was observed to lower serum ADMA levels in type 2 DM patients. Our findings notwithstanding, large-scale prospective randomized controlled studies are warranted to conclude that vildagliptin provides cardiovascular protection along with diabetes regulation.

Absolute blood eosinophil count and 1-year mortality risk following hospitalization with acute heart failure.

Objective In acute heart failure (AHF), hemoglobin, red cell distribution width, mean platelet volume, leukocytes, and relative lymphocyte count have been associated with mortality. It is not known whether absolute blood neutrophil, eosinophil, and monocyte counts are mortality predictors. Methods One hundred and seventy-six patients hospitalized due to AHF were enrolled. Treatment modalities and comorbidities influencing leukocyte counts were excluded. Hemogram, pro-brain natriuretic peptide, D-dimer, biochemistry, thyroid hormones, sensitive C-reactive protein, and echocardiography were obtained. Cardiovascular deaths during the first year after hospitalization were determined. Results Leukocyte and absolute neutrophil count were significantly higher and absolute lymphocyte count and absolute eosinophil count (AEC) were significantly lower in deceased patients than patients who survived. Groups were similar in terms of monocyte counts. BMI albumin, estimated glomerular filtration rate, free T3, ejection fraction were significantly lower, and ferritin, uric acid, D-dimer, pro-brain natriuretic peptide were significantly higher in deceased patients. Mitral regurgitation, hypotension, hyponatremia, and acute renal failure were also significantly more frequent among the deceased group. Binary logistic regression analysis employing significant variables showed that lower BMI, lower ejection fraction, hyponatremia, lower free T3, and lower AEC were independent predictors of death and as a whole were responsible from 81.8% of cardiovascular deaths. Death rate among patients with an AEC of 0.02 n/l×109 or less was 4.4-fold higher than patients with an AEC of more than 0.02 n/l×109. Conclusion AEC of AHF patients measured at admission was found to be a stronger predictor of mortality than all other hemogram parameters and this is consistent with the increased sympatho-adrenal activity theory.