Gamma glutamyltransferase, alanine aminotransferase and risk of cancer : systematic review and meta-analysis

The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is uncertain. We conducted a systematic review and meta-analysis of published prospective observational studies evaluating the associations of baseline levels of GGT and ALT with risk of overall (incidence and/or mortality) and site-specific cancers. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, reference lists of relevant studies to April 2014 and email contact with investigators. Study specific relative risks (RRs) were meta-analyzed using random effects models. Fourteen cohort studies with data on 1.79 million participants and 57,534 cancer outcomes were included. Comparing top versus bottom thirds of baseline circulating GGT levels, pooled RRs (95% confidence intervals) were 1.32 (1.15-1.52) for overall cancer, 1.09 (0.95-1.24) for cancers of the breast and female genital organs, 1.09 (1.02-1.16) for cancers of male genital organs, 1.94 (1.35-2.79) for cancers of digestive organs and 1.33 (0.94-1.89) for cancers of respiratory and intrathoracic organs. For ALT, corresponding RRs for overall cancer were 0.96 (0.94-0.99) and 1.65 (1.52-1.79) in European and Asian populations, respectively. There was an increased risk of cancers of the digestive organs 2.44 (1.23-4.84). The pooled RR for overall cancer per 5 U/L increment in GGT levels was 1.04 (1.03-1.05). Available observational data indicate a positive log-linear association of GGT levels with overall cancer risk. The positive association was generally evident for site-specific cancers. There are geographical variations in the association of ALT and overall cancer

Supplementary Material for: Haemodynamic gain index is associated with risk of sudden cardiac death and improves risk prediction: a cohort study

Introduction: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study. Methods: Haemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) measured in 1897 men aged 42-61 years during CPX from rest to peak exercise, using the formula: [(Heart rate max x SBPmax) - (Heart rate rest x SBPrest)]/(Heart rate rest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were analyzed for SCD. Results: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p-value for non-linearity=.63). A unit (bpm/mmHg) higher HGI was associated with a decreased risk of SCD (HR 0.84; 95% CI 0.71–0.99), which was attenuated following adjustment for CRF. Cardiorespiratory fitness was inversely associated with SCD, which remained after further adjustment for HGI: (HR 0.85; 95% CI 0.77–0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change=0.0096; p=.017) and reclassification (NRI=39.40%, p=.001). The corresponding values for CRF were (C-index change=0.0178; p=.007) and (NRI=43.79%, p=.001). Conclusion: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship, but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI

Supplementary Material for: Haemodynamic gain index is associated with risk of sudden cardiac death and improves risk prediction: a cohort study

Introduction: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study. Methods: Haemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) measured in 1897 men aged 42-61 years during CPX from rest to peak exercise, using the formula: [(Heart rate max x SBPmax) - (Heart rate rest x SBPrest)]/(Heart rate rest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were analyzed for SCD. Results: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p-value for non-linearity=.63). A unit (bpm/mmHg) higher HGI was associated with a decreased risk of SCD (HR 0.84; 95% CI 0.71–0.99), which was attenuated following adjustment for CRF. Cardiorespiratory fitness was inversely associated with SCD, which remained after further adjustment for HGI: (HR 0.85; 95% CI 0.77–0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change=0.0096; p=.017) and reclassification (NRI=39.40%, p=.001). The corresponding values for CRF were (C-index change=0.0178; p=.007) and (NRI=43.79%, p=.001). Conclusion: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship, but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI

Serum Albumin and Future Risk of Hip, Humeral, and Wrist Fractures in Caucasian Men : New Findings from a Prospective Cohort Study

Objective: Low serum albumin concentration is associated with poor health outcomes, but its relationship with the risk of fractures has not been reliably quantified. We aimed to assess the prospective association of serum albumin with the risk of fractures in a general population. Subjects and Methods: Baseline serum albumin concentrations were measured in 2,245 men aged 42–61 years in the Kuopio Is­chemic Heart Disease study. Hazard ratios (HRs) (95% confidence intervals) were calculated for incident fractures. Results: A total of 121 fractures (hip, humeral, or wrist) were recorded during a median follow-up of 25.6 years. The risk of fractures increased linearly below a serum albumin concentration of ∼48 g/L. The age-adjusted HR (95% CI) for fractures per 1 standard deviation lower serum albumin was 1.24 (1.05–1.48). On further adjustment for several conventional and emerging risk factors, the HR was attenuated to 1.21 (1.01–1.45). Comparing the bottom versus top quartile of serum albumin levels, the corresponding adjusted HRs were 2.48 (1.37–4.48) and 2.26 (1.23–4.14). The association of serum albumin with fracture risk did not differ substantially according to age, body mass index, blood pressure, physical activity, alcohol consumption, socioeconomic status, inflammation, prevalent diseases, and smoking. Serum albumin at a threshold of 41.5 g/L demonstrated an area under the curve of 0.5850. Conclusion: In middle-aged Caucasian men, low serum albumin is associated with an increased risk of future fractures. The potential relevance of serum albumin concentrations in fracture prevention and prediction deserves further evaluation.peerReviewe

The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection: A Systematic Review and Meta-Analysis.

Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this systematic review and meta-analysis was to synthesize the evidence on the accuracy of the alpha-defensin immunoassay and leukocyte esterase colorimetric strip test for the diagnosis of PJI compared with the Musculoskeletal Infection Society diagnostic criteria