Contribution of 30 Biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: The MONICA, risk, genetics, archiving and monograph (MORGAM) biomarker project

Background— Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study.
Methods and Results— Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008).
Conclusions— The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.

The finding of reduced estimated glomerular filtration rate is associated with increased mortality in a large UK population

BACKGROUND: CKD as defined by KDIGO/KDOQI has been shown to affect ~ 8.5% of the UK population. The prevalence of CKD in the UK is similar to that in the USA, yet incident dialysis rates are dramatically different. This retrospective cohort study investigates the association between reduced kidney function and mortality in a large UK population. METHODS: All serum creatinine results covering Northern Ireland's 1.7 million population were collected between 1 January 2001 and 31 December 2002. Estimated glomerular filtration rates (eGFR) were calculated for all serum creatinine measurements using four-variable MDRD equation (IDMS aligned). Patients were followed up for both all-cause and cardiovascular mortality data until the end of December 2006. Patients on renal replacement therapy were excluded. Subgroup analysis in the 75 345 subjects enrolled within a parallel primary care study permitted additional survival analysis with adjustment for traditional cardiovascular risk factors. RESULTS: A total of 1 967 827 serum creatinine results from 533 798 patients were collected. During the period of follow-up, 59 980 deaths occurred. In multivariate survival analysis, using eGFR as a time-varying covariate, a graded association between CKD (defined by eGFR) and all-cause mortality was identified. Compared with participants with an eGFR of > 60 mL/min/1.73 m(2), the adjusted hazard ratios (and 95% confidence intervals) for participants with an eGFR of 45-59 mL/min/1.73 m(2) was 1.02 (0.99-1.04), an eGFR of 30-44 mL/min/1.73 m(2) was 1.44 (1.40-1.47), an eGFR of 15-29 mL/min/1.73 m(2) was 2.12 (2.05-2.20) and an eGFR of

Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case-control study

Background: The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown.

A Population-Based Study of IGF Axis Polymorphisms and the Esophageal Inflammation, Metaplasia, Adenocarcinoma Sequence

BACKGROUND & AIMS: Insulin-like growth factor (IGF) axis plays a key role in cell development, proliferation, and survival and is implicated in the etiology of several cancers. Few studies have examined the relationship between genetic variation of this axis and esophageal adenocarcinoma (EAC) or its precursors. METHODS: In a population-based case-control study, we investigated the association of common polymorphisms of IGF-1, IGF-2, IGF-1 receptor, IGF binding protein -3, growth hormones (GH) 1 and GH2, and GH receptor with reflux esophagitis (RE), Barrett esophagus (BE), and EAC. Two hundred and thirty RE, 224 BE, 227 EAC cases, and 260 controls were studied. Gene polymorphisms were identified using publicly available online resources; 102 IGF axis tag and putatively functional single-nucleotide polymorphisms (SNPs) were analyzed using MassARRAY iPLEX and Taqman assays. Results were analyzed using Haploview.
RESULTS: Three polymorphisms were disease-associated. IGF1 SNP rs6214 was associated with BE (adjusted P = .039). Using GG genotype as reference, odds ratio for BE in AA (wild-type) was 0.43 (95% confidence interval [CI], 0.24-0.75). GH receptor SNP rs6898743 was associated with EAC (adjusted P = .0112). With GG as reference, odds ratio for EAC in CC (wildtype) genotype was 0.42 (95% CI, 0.23-0.76). IGF1 (CA)(17) 185-bp allele was associated with RE (adjusted P = .0116). Using IGF1(non17) as reference, odds ratio for RE in IGF1(17) carriers was 7.29 (95% CI, 1.57-46.7).
CONCLUSIONS: In this study, 3 polymorphisms of IGF genes were associated with EAC or its precursors. These polymorphisms may be markers of disease risk; independent validation of our findings is required. These results suggest the IGF pathway is involved in EAC development.