Associations of dyslipidaemia and lipid-lowering treatment with risk of postoperative cognitive dysfunction: a systematic review and meta-analysis

BACKGROUND: Lipid imbalance is linked to age-related cognitive impairment, but its role in postoperative cognitive dysfunction (POCD) is unknown. Here, we present a systematic review and meta-analysis on dyslipidaemia, lipid-lowering treatment and POCD risk. METHODS: PubMed, Ovid SP and Cochrane databases were searched for longitudinal studies that reported on associations of any measure of dyslipidaemia and/or lipid-lowering treatment with POCD as relative risks (RRs) or ORs. Fixed-effects inverse variance models were used to combine effects. RESULTS: Of 205 articles identified in the search, 17 studies on 2725 patients (grand mean age 67 years; mean age range 61-71 years) with follow-up periods of 1 day to 4 years (median 7 days; IQR 1-68 days) were included. Studies focused almost exclusively on hypercholesterolaemia as a measure of dyslipidaemia and on statins as lipid-lowering treatment. Across 12 studies on hypercholesterolaemia, we found no association with POCD risk (RR 0.93; 95% CI 0.80 to 1.08; P=0.34). Statin use before surgery was associated with a reduced POCD risk across eight studies (RR 0.81; 95% CI 0.67 to 0.98; P=0.03), but data on treatment duration were lacking. CONCLUSION: Statin users appear to be at reduced risk of POCD although hypercholesterolaemia per se may not be associated with POCD risk. Trial studies are needed to evaluate the usefulness of statins in POCD prevention

Prediction of activity related energy expenditure using accelerometer derived physical activity under free-living conditions-a systematic review

BACKGROUND: Activity related energy expenditure (AEE) might be an important factor in the etiology of chronic diseases. However, measurement of free-living AEE is usually not feasible in large scale epidemiological studies but instead has traditionally been estimated based on self-reported physical activity. Recently, accelerometry has been proposed for objective assessment of physical activity, but it is unclear to what extent this methods explains the variance in AEE. METHODS: We conducted a systematic review searching MEDLINE database (until 2014) on studies that estimated AEE based on accelerometry-assessed physical activity in adults under free-living conditions (using doubly-labeled water method). Extracted study characteristics: sample size, accelerometer (type [uniaxial, triaxial], metrics [e.g. activity counts, steps, acceleration], recording period, body position, wear time), explained variance of AEE (R2), number of additional predictors. The relation of univariate and multivariate R2 with study characteristics was analyzed using non-parametric tests. RESULTS: Nineteen articles were identified. Examination of various accelerometers or subpopulations in one article was treated separately, resulting in 28 studies. Sample sizes ranged from 10-149. In most studies the accelerometer was triaxial, worn at the trunk, during waking hours, and reported activity counts as output metric. Recording periods ranged from 5-15 days. The variance of AEE explained by accelerometer assessed physical activity ranged from 4-80% (median crude R2=26%). Sample size was inversely related to the explained variance. Inclusion of 1 to 3 other predictors in addition to accelerometer output significantly increased the explained variance to a range of 12.5-86% (median total R2=41%). The increase did not depend on the number of added predictors. CONCLUSIONS: We conclude that there is large heterogeneity across studies in the explained variance of AEE when estimated based on accelerometry. Thus, data on predicted AEE based on accelerometry assessed physical activity need to be interpreted cautiously

Influence of obesity and related metabolic alterations on colorectal cancer risk

Obesity and related metabolic alterations have been implicated to play a role in colorectal cancer risk. The metabolic syndrome, as assessed according to current international definitions by the key components, abdominal obesity, dyslipidemia, elevated blood pressure, and abnormal glucose metabolism, is associated with colorectal cancer. Recent studies suggest that abdominal obesity and abnormal glucose metabolism may primarily account for this association. Visceral adipose tissue is physiologically more active than subcutaneous adipose tissue and generates hormones and cytokines with inflammatory, metabolic, and direct carcinogenic potential, which may directly or indirectly increase colorectal cancer risk. Current evidence suggests that obesity acts as a risk factor for colorectal cancer by several mechanisms, including chronic low-grade inflammation, hyperinsulinemia, as well as alterations in insulin-like growth factor and adipokine concentrations. Metabolic biomarkers reflecting these processes may not only provide clues for etiological understanding of colorectal carcinogenesis but also might be an alternative way to define an "obesity phenotype" that is relevant for colorectal cancer development

Hypertension and risk of post-operative cognitive dysfunction (POCD): a systematic review and meta-analysis

BACKGROUND: Post-operative cognitive dysfunction (POCD) occurs frequently after major surgery. Hypertension is well-established as a risk factor for age-related cognitive impairment, but it is unclear whether or not it also increases the risk of POCD. OBJECTIVE: To evaluate the role of hypertension in POCD risk in a systematic review and meta-analysis. METHOD: PubMed, Ovid SP and the Cochrane Database of Systematic Reviews were searched for longitudinal studies of adults undergoing surgery with reporting of hypertension, blood pressure and/or anti-hypertensive treatment associations with POCD as relative risks or odds ratios. Fixed-effects meta-analyses were performed using Review Manager (version 5.3). RESULTS: Twenty-four studies on 4317 patients (mean age 63 years) were included. None of the studies had set out to assess hypertension as a risk factor for POCD. Hypertension was used as a categorical predictor throughout and only 2 studies adjusted for potential confounders. Across all 24 studies, hypertension was not significantly associated with POCD risk (RR 1.01; 95% CI 0.93, 1.09; p=0.82), though among 8 studies with >75% males, we found hypertension associations with a 27% increased risk of POCD (RR 1.27, 95% CI 1.07, 1.49; p=0.005). CONCLUSION: Our findings do not support the hypothesis that hypertension is a risk factor for POCD. However, since none of the studies included in our analysis were hypothesis-driven and most did not adjust for potential confounders, further systematic investigations are needed to evaluate the role of hypertension in the epidemiology of POCD

Genetic association analysis based on a joint model of gene expression and blood pressure

Recent work on genetic association studies suggests that much of the heritable variation in complex traits is unexplained, which indicates a need for using more biologically meaningful modeling approaches and appropriate statistical methods. In this study, we propose a biological framework and a corresponding statistical model incorporating multilevel biological measures, and illustrate it in the analysis of the real data provided by the Genetic Analysis Workshop (GAW) 19, which contains whole genome sequence (WGS), gene expression (GE), and blood pressure (BP) data. We investigate the direct effect of single-nucleotide variants (SNVs) on BP and GE, while considering the non-directional dependence between BP and GE, by using copula functions to jointly model BP and GE conditional on SNVs. We implement the method for analysis on a genome-wide scale, and illustrate it within an association analysis of 68,727 SNVs on chromosome 19 that lie in or around genes with available GE measures. Although there is no indication for inflated type I errors under the proposed method, our results show that the association tests have smaller p values than tests under univariate models for common and rare variants using single-variant tests and gene-based multimarker tests. Hence, considering multilevel biological measures and modeling the dependence structure between these measures by using a plausible graphical approach may lead to more informative findings than standard univariate tests of common variants and well-recognized gene-based rare variant tests

Adipositas und Krebs [Obesity and risk of cancer]

There is growing scientific evidence that overweight and obesity are associated with increased risk of cancer. So far, there is convincing evidence from epidemiological studies that obesity is associated with a higher risk of colorectal cancer, postmenopausal breast cancer, endometrial cancer, renal cell cancer, esophageal adenocarcinoma and pancreatic cancer. A 5 unit increase in body mass index is associated with a 12 % to 51 % higher risk. Abdominal obesity is associated with esophageal adenocarcinoma and colorectal cancer beyond body mass index. Obesity has also been associated with a higher risk of liver and ovarian cancer, although supporting data is less abundant. The mechanisms underlying the positive association between obesity and risk of certain cancers have not been fully elucidated and differ by cancer site. Among the most important potential mechanisms are components of the metabolic syndrome, in particular insulin resistance and hyperinsulinemia, chronic inflammatory processes, sex steroid hormones as well as cytokines secreted by adipose tissue, including leptin and adiponectin

Increased periodontal attachment loss in patients with systemic sclerosis

Background: Patients with inflammatory rheumatic diseases and periodontitis share common pathogenetic characteristics, such as pro-inflammatory traits causative for tissue degradation and loss of function. Aim of the present case control study was to investigate the association between systemic sclerosis (SSc) and periodontitis. Methods: The association between SSc and periodontitis was examined in 58 SSc patients and 52 control patients, matched for age and gender. Periodontal examination included periodontal attachment loss, probing pocket depth, bleeding on probing, plaque index and gingival index. Potential risk factors of periodontitis were assessed through patients' questionnaires. Results: In unadjusted analyses, patients with SSc had a significant 0.61 mm higher periodontal attachment loss (95 % confidence interval (CI), 0.24 - 0.97; p = 0.002) when compared to controls. In a stepwise logistic regression, including SSc status, age, gender, education, smoking, alcohol consumption and BMI, only SSc status, age, and gender remained significantly associated with periodontitis. Adjusted for age and gender, patients with SSc had 0.52 mm higher periodontal attachment loss compared to controls (95 % CI, 0.16 - 0.88; p = 0.005). The strength of the association of SSc with periodontal attachment loss remained statistically significant after further adjustment for plaque index (0.44 mm; 95 % CI 0.02 - 0.86; p = 0.038) or gingival index (0.61 mm; 95 % CI, 0.24 - 0.97 p = 0.001). Conclusions: The study demonstrates higher periodontal clinical attachment loss in SSc patients, which remained significant following adjustment. The study indicates a possible relationship between SSc and periodontitis

Plasma leptin, but not adiponectin, is associated with cognitive impairment in older adults

BACKGROUND: Leptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults. METHODS: Cross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014–2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests. RESULTS: After adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI < 30 kg/m2), whereas leptin and LAR were not associated with cognitive impairment in the obese group (BMI ≥ 30 kg/m2). Soluble leptin receptor, leptin/soluble leptin receptor ratio, total adiponectin and high-molecular weight adiponectin concentrations were each not associated with impairment. CONCLUSIONS: With leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation