All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study.

BACKGROUND: Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide, particularly in low to middle-income countries with high disease burden and limited treatment availability. Coffee consumption has been linked with lower rates of CLD, but little is known about the effects of different coffee types, which vary in chemical composition. This study aimed to investigate associations of coffee consumption, including decaffeinated, instant and ground coffee, with chronic liver disease outcomes. METHODS: A total of 494,585 UK Biobank participants with known coffee consumption and electronic linkage to hospital, death and cancer records were included in this study. Cox regression was used to estimate hazard ratios (HR) of incident CLD, incident CLD or steatosis, incident hepatocellular carcinoma (HCC) and death from CLD according to coffee consumption of any type as well as for decaffeinated, instant and ground coffee individually. RESULTS: Among 384,818 coffee drinkers and 109,767 non-coffee drinkers, there were 3600 cases of CLD, 5439 cases of CLD or steatosis, 184 cases of HCC and 301 deaths from CLD during a median follow-up of 10.7 years. Compared to non-coffee drinkers, coffee drinkers had lower adjusted HRs of CLD (HR 0.79, 95% CI 0.72-0.86), CLD or steatosis (HR 0.80, 95% CI 0.75-0.86), death from CLD (HR 0.51, 95% CI 0.39-0.67) and HCC (HR 0.80, 95% CI 0.54-1.19). The associations for decaffeinated, instant and ground coffee individually were similar to all types combined. CONCLUSION: The finding that all types of coffee are protective against CLD is significant given the increasing incidence of CLD worldwide and the potential of coffee as an intervention to prevent CLD onset or progression.

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function. STUDY DESIGN: Genome-wide association study (GWAS) and Mendelian randomization. SETTING & PARTICIPANTS: UK Biobank baseline data were used for a coffee consumption GWAS and included 227,666 participants. CKDGen Consortium data were used for kidney outcomes and included 133,814 participants (12,385 cases of CKD) of mostly European ancestry across various countries. EXPOSURE: Coffee consumption. OUTCOMES: Estimated glomerular filtration rate (eGFR), CKD GFR categories 3 to 5 (G3-G5; eGFR<60mL/min/1.73m2), and albuminuria. ANALYTICAL APPROACH: GWAS to identify single-nucleotide polymorphisms (SNPs) associated with coffee consumption in UK Biobank and use of those SNPs in Mendelian randomization analyses of coffee consumption and kidney outcomes in CKDGen. RESULTS: 2,126 SNPs were associated with coffee consumption (P<5×10-8), 25 of which were independent and available in CKDGen. Drinking an extra cup of coffee per day conferred a protective effect against CKD G3-G5 (OR, 0.84; 95% CI, 0.72-0.98; P=0.03) and albuminuria (OR, 0.81; 95% CI, 0.67-0.97; P=0.02). An extra cup was also associated with higher eGFR (ß=0.022; P=1.6×10-6) after removal of 3 SNPs responsible for significant heterogeneity (Cochran Q P = 3.5×10-15). LIMITATIONS: Assays used to measure creatinine and albumin varied between studies that contributed data and a sex-specific definition was used for albuminuria rather than KDIGO guideline recommendations. CONCLUSIONS: This study provides evidence of a beneficial effect of coffee on kidney function. Given widespread coffee consumption and limited interventions to prevent CKD incidence and progression, this could have significant implications for global public health in view of the increasing burden of CKD worldwide.

Misclassification of coffee consumption data and the development of a standardised coffee unit measure.

BACKGROUND: Associations of coffee consumption with multiple health outcomes have been researched extensively. Coffee consumption, usually reported in cups a day, is a heterogeneous measure due to numerous preparation methods and cup sizes, leading to misclassification. This paper develops a new 'unit' measure of coffee and uses coffee consumption data from a representative sample of the UK population to assess misclassification when cup volume and preparation type are not taken into account. METHODS: A coffee unit measure was created using published estimates of caffeine and chlorogenic acid concentrations, and applied across volumes and preparation types. Four-day food diary data in adults from the UK National Diet and Nutrition Survey (NDNS; 2012-2016) were used to quantify coffee intake. Participant self-reported cups a day were compared with cups a day standardised by (a) 227 mL volume and (b) 227 mL instant coffee equivalents (unit measure), and the degree of misclassification was derived. Sensitivity analyses were conducted to model coffee drinking preferences of different populations and caffeine:chlorogenic acid weighting assumptions of the unit measure. RESULTS: The NDNS sample consisted of 2832 adult participants. Coffee was consumed by 62% of participants. Types varied, with 75% of caffeinated coffee cups being instant, 17% filter, 3% latte, 2% cappuccino, 2% espresso and <1% other types. Comparing reported cups to volume-standardised cups, 84% of participants had correct classification, and 73% when using the coffee unit measure, 22% underestimated and 5% overestimated, largely by one cup. Misclassification varied by gender, age and income. Sensitivity analysis highlighted the benefits of using the unit measure over volume alone to cater for different populations, and stability of the unit composition assumption. CONCLUSION: Cup volume and preparation type should be taken into account, through the application of a standardised coffee unit measure, when coffee consumption is classified in future research studies.

What is the association between healthy weight in 4-5-year-old children and spatial access to purposefully constructed play areas?

BACKGROUND: Childhood obesity is a global issue. Understanding associated factors is essential in designing interventions to reduce its prevalence. There are knowledge gaps concerning the leptogenic potential of play areas for very young children and particularly whether there is an association between levels of childhood obesity and play area quality. METHODS: A cross-sectional observational study was conducted to investigate whether spatial access to play areas had an association with healthy weight status of 4-5-year-old children. Data from the English National Childhood Measurement Programme 2012/13 was used to measure healthy weight status and a geographic information system was used to calculate (a) the number of purposefully constructed play areas within 1km (density), and (b) the distance to nearest play area (proximity), from child's residential postcode. A play area quality score was included in predictive models. Multilevel modelling was used to adjust for the clustering of observations by school. Adjustment was also made for the effects of gender and deprivation. RESULTS: 77% of children had a healthy weight status (≥2nd and <85th centile). In a fully adjusted multilevel model there was no statistically significant association between healthy weight status and density or proximity measures, with or without inclusion of a play area quality score, or when accounting for the effects of gender and deprivation. CONCLUSIONS: Among 4-5-year-old children attending school, there was no association between healthy weight status and spatial access to play areas. Reasons may include under-utilisation of play areas by reception age children, their minimal leptogenic influence or non-spatial influences affecting play area choice.

Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes.

Objectives To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes.Design Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome.Data sources PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references.Eligibility criteria for selecting studies Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded.Results The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83 (95% confidence interval 0.79 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions. Harmful associations were largely nullified by adequate adjustment for smoking, except in pregnancy, where high versus low/no consumption was associated with low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and second (1.12, 1.02 to 1.22) trimester, and pregnancy loss (1.46, 1.06 to 1.99). There was also an association between coffee drinking and risk of fracture in women but not in men.Conclusion Coffee consumption seems generally safe within usual levels of intake, with summary estimates indicating largest risk reduction for various health outcomes at three to four cups a day, and more likely to benefit health than harm. Robust randomised controlled trials are needed to understand whether the observed associations are causal. Importantly, outside of pregnancy, existing evidence suggests that coffee could be tested as an intervention without significant risk of causing harm. Women at increased risk of fracture should possibly be excluded.

Prediction of progression of damage to articular cartilage 2 years after anterior cruciate ligament reconstruction: use of aggrecan and type II collagen biomarkers in a retrospective observational study.

BACKGROUND: We aimed to determine whether synovial fluid (SF) biomarkers can predict the progression of articular cartilage damage as determined by arthroscopic evaluation during and after anterior cruciate ligament (ACL) reconstruction. METHODS: Arthroscopic assessment of articular cartilage damage was performed twice in 62 patients, first during ACL reconstruction and then approximately 2 years later during implant removal for ligament fixation. SF levels of the collagenase-generated cleavage neoepitope of type II collagen (C2C) and proteoglycan glycosaminoglycans keratan sulfate (KS), chondroitin-4-sulfate (Δdi-C4S), and chondroitin-6-sulfate (Δdi-C6S) were measured at ACL reconstruction. Associations between baseline biomarker levels and subsequent progression of cartilage damage were determined using receiver operating characteristic analysis and multivariable logistic regression analysis. RESULTS: No radiographic changes were observed in any of the patients. Progression of high-grade cartilage damage, observed arthroscopically, was negatively correlated with levels of Δdi-C6S and KS, as well as the ratio of Δdi-C6S to Δdi-C4S (C6S/C4S). Logistic regression analysis revealed significant associations of Δdi-C6S (cut-off: 55.7 nmol/ml, odds ratio (OR) 0.231, 95% confidence interval (CI) 0.061-0.879), KS (cut-off: 10.6 µg/ml, OR 0.114, 95% CI 0.024-0.529), and C6S/C4S ratio (cut-off: 4.6, OR 0.060, 95% CI 0.005-0.737) with the progression of high-grade cartilage damage after adjusting for age, the duration from injury to first surgery, sex, and the number of high-grade lesions (grades III and IV) at baseline. CONCLUSIONS: The progression of high-grade cartilage damage was significantly associated with baseline levels of proteoglycan glycosaminoglycan biomarkers; namely, Δdi-C6S, KS, and C6S/C4S ratio.

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.

INTRODUCTION: We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism. METHODS: Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA). RESULTS: sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA. CONCLUSIONS: These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

Biochemical markers of bone turnover and their association with bone marrow lesions.

INTRODUCTION: Our objective was to determine whether markers of bone resorption and formation could serve as markers for the presence of bone marrow lesions (BMLs). METHODS: We conducted an analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS). Knee magnetic resonance images were scored for BMLs using a semiquantitative grading scheme. In addition, a subset of persons with BMLs underwent quantitative volume measurement of their BML, using a proprietary software method. Within the BOKS population, 80 people with BMLs and 80 without BMLs were selected for the purposes of this case-control study. Bone biomarkers assayed included type I collagen N-telopeptide (NTx) corrected for urinary creatinine, bone-specific alkaline phosphatase, and osteocalcin. The same methods were used and applied to a nested case-control sample from the Framingham study, in which BMD assessments allowed evaluation of this as a covariate. Logistic regression models were fit using BML as the outcome and biomarkers, age, sex, and body mass index as predictors. An receiver operating characteristic curve was generated for each model and the area under the curve assessed. RESULTS: A total of 151 subjects from BOKS with knee OA were assessed. The mean (standard deviation) age was 67 (9) years and 60% were male. Sixty-nine per cent had maximum BML score above 0, and 48% had maximum BML score above 1. The only model that reached statistical significance used maximum score of BML above 0 as the outcome. Ln-NTx (Ln is the natural log) exhibited a significant association with BMLs, with the odds of a BML being present increasing by 1.4-fold (95% confidence interval = 1.0-fold to 2.0-fold) per 1 standard deviation increase in the LnNTx, and with a small partial R2 of 3.05. We also evaluated 144 participants in the Framingham Osteoarthritis Study, whose mean age was 68 years and body mass index was 29 kg/m2, and of whom 40% were male. Of these participants 55% had a maximum BML score above 0. The relationship between NTx and maximum score of BML above 0 revealed a significant association, with an odds ratio fo 1.7 (95% confidence interval = 1.1 to 2.7) after adjusting for age, sex, and body mass index. CONCLUSIONS: Serum NTx was weakly associated with the presence of BMLs in both study samples. This relationship was not strong and we would not advocate the use of NTx as a marker of the presence of BMLs.

Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee Study.

We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4C(short) or C1,2C), type II cleavage only with Col2:3/4C(longmono) (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels.

Direct evidence of collagenolysis in chronic periodontitis.

BACKGROUND: There is no previous evidence that collagenases in chronic periodontitis excessively cleave collagen fibrils. OBJECTIVES: In this study the eventual presence of neoepitopes produced in such a cleavage were looked for. METHODS: A polyclonal antibody, which recognizes collagenase-cleaved collagen type I 3/4 carboxy-terminal neoepitope (COL1-3/4C), was used in avidin-biotin-peroxidase complex staining. RESULTS: In addition, moderate staining was seen in connective tissue bordering to the sulcular and junctional epithelium, surrounding some of the fibroblasts and in some areas infiltrated by inflammatory mononuclear cells. COL1-3/4C staining in chronic periodontitis was more extensive (6.3 +/- 1.2%, n = 10) and intense than that observed in controls (1.6 +/- 0.7%, n = 10, Unpaired Student's t-test, p < 0.01). CONCLUSIONS: It is concluded that collagenases produced by host cells contribute to periodontal tissue destruction and attachment loss.