Journal of internal medicine
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Randomized Controlled Trial
The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: results from CORONA*.
To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. ⋯ We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n = 307) and all-cause mortality (n = 321), cardiovascular mortality (n = 259) and hospitalization (n = 647) as well as the number of hospitalizations during follow-up for all (n = 1934) and CV causes (n = 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points.
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Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality and healthcare costs in the western world. Although smoking is an important trigger of COPD, other factors such as chronic inflammation and malnutrition are known to influence its development. Because coeliac disease (CD) is characterized both by dysregulated inflammation and malnutrition, the possibility of an association between CD and COPD was investigated. ⋯ During follow-up, 380 individuals with CD (3.5%) and 1391 (2.6%) controls had an incident diagnosis of COPD, which corresponds to an HR of 1.24 (95% CI: 1.10-1.38) and an excess risk of COPD of 79/100 000 person-years in CD. The risk increase remained 5 years after biopsy (HR = 1.17; 95% CI: 1.00-1.37). Risk estimates did not change with adjustment for type 1 diabetes, thyroid disease, rheumatoid arthritis, country of birth or level of education. Men with CD were at a higher risk of COPD (HR = 1.39; 95% CI: 1.18-1.62) than women with CD (HR = 1.11; 95% CI: 0.94-1.30). Of note, CD was also associated with COPD before CD diagnosis (odds ratio = 1.22; 95% CI: 1.02-1.46). Conclusion. Patients with CD seem to be at a moderately increased risk of COPD both before and after CD diagnosis.
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The individual human genome and epigenome are being defined at unprecedented resolution by current advances in sequencing technologies with important implications for human disease. This review uses examples relevant to clinical practice to illustrate the functional consequences of genetic and epigenetic variation. The insights gained from genome-wide association studies are described together with current efforts to understand the role of rare variants in common disease, set in the context of recent successes in Mendelian traits through the application of whole exome sequencing. The application of functional genomics to interrogate the genome and epigenome, build up an integrated picture of the regulatory genomic landscape and inform disease association studies is discussed, together with the role of expression quantitative trait mapping and analysis of allele-specific gene expression.
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Prostate cancer is the commonest cancer in the developed world. There is an inherited component to this disease as shown in familial and twin studies. However, the discovery of these variants has been difficult. ⋯ Their clinical utility to predict risk, response to treatment, or treatment toxicity, remains undefined. Large consortia are needed to achieve adequate statistical power to answer these genetic-clinical and genetic-epidemiological questions. International collaborations are currently underway to link genetic with clinical/epidemiological data to develop risk prediction models, which could direct screening and treatment programs.
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Breast cancer is not only increasing in the west but also particularly rapidly in eastern countries where traditionally the incidence has been low. The rise in incidence is mainly related to changes in reproductive patterns and lifestyle. These trends could potentially be reversed by defining women at greatest risk and offering appropriate preventive measures. ⋯ However, referral to FHCs is opportunistic and predominantly includes younger women. A better approach for identifying older women at risk may be to use national breast screening programmes. Here were described pilot studies to assess whether the routine assessment of breast cancer risk is feasible within a population-based screening programme, whether the feedback and advice on risk-reducing interventions would be welcomed and taken up, and to consider whether the screening interval should be modified according to breast cancer risk.