[Use of troponin analysis in Norwegian hospitals]. / Bruk av troponinmålinger i norske sykehus.

BACKGROUND: A highly sensitive troponin T analysis became available in Norway in 2009. The Norwegian Society of Medical Biochemistry believed that a national strategy for implementation of the analysis would ensure a more coherent practice for diagnosing acute myocardial infarction (AMI). MATERIAL AND METHODS: 70 laboratories were requested to identify (in a questionnaire) the type of assay used, routines for reporting results of analyses, internal quality control programmes (IQA) and local cut-off values for making the diagnosis AMI. RESULTS: 62 laboratories responded and 57 of these analyzed troponins; 60 % used troponin T and 40 % troponin I. 82 % of laboratories were familiar with the decision limit used for diagnosing AMI at their hospital; 43 % of troponin T laboratories used the cut-off recommended by the Norwegian Society of Cardiology (0.03 microg/l) to diagnose AMI. For the two most used troponin I methods (16 laboratories) eight different cut-off values were reported. 24 % (troponin T) and 35 % (troponin I) of laboratories performed IQA at a concentration similar or lower than the local decision limit used when diagnosing AMI. 73 % (troponin T) and 54 % (troponin I) of laboratories used the lower limit of quantification as the lower cut-off value for reportable results. INTERPRETATION: In Norwegian hospitals, users of the same methods for analysis of troponin have different routines for interpreting, IQA and reporting of results. Patient diagnoses may therefore vary according to the hospital used. The Norwegian Society of Medical Biochemistry has developed recommendations for implementation of troponin analyses in Norwegian laboratories.

Dysregulated RANK ligand/RANK axis in hyperhomocysteinemic subjects: effect of treatment with B-vitamins.

BACKGROUND AND PURPOSE: Homocysteine has been linked to increased risk of ischemic stroke and other cardiovascular events. Matrix degradation and inflammation play an important role in these disorders, and we have demonstrated increased levels of matrix-degrading enzymes and inflammatory cytokines in hyperhomocysteinemic individuals. Recent studies suggest that RANK ligand (RANKL) through interaction with its receptor RANK can modulate matrix degradation and inflammation. The present study aimed to examine the role of the RANKL/RANK axis in hyperhomocystinemia. METHODS: RANKL/RANK was measured on protein or mRNA level before and after B-vitamin supplementation in hyperhomocysteinemic individuals. We also examined the in vitro effects of soluble RANKL in peripheral blood mononuclear cells from hyperhomocysteinemic individuals. RESULTS: Our main findings were: (1) compared to peripheral blood mononuclear cells from controls, cells from hyperhomocysteinemic individuals had significantly higher gene expression of RANKL and RANK; (2) folic acid treatment for 6 weeks in an open, uncontrolled study significantly reduced gene expression of RANKL/RANK in peripheral blood mononuclear cells from these individuals; (3) compared to placebo, treatment with folic acid, vitamin B(12), and vitamin B(6) for 3 months in a randomized, double-blind trial significantly lowered serum levels of soluble RANKL in hyperhomocysteinemic individuals; and (4) in vitro, soluble RANKL markedly increased the release of matrix metalloproteinase-9 and inflammatory cytokines from peripheral blood mononuclear cells in hyperhomocysteinemic subjects. CONCLUSIONS: Our findings suggest a dysregulated RANKL/RANK axis in hyperhomocysteinemic subjects. Based on their role in atherogenesis, this enhanced expression of RANKL and RANK could contribute to the increased risk of cardiovascular disease in hyperhomocystinemia. Moreover, treatment with B-vitamins may have beneficial implications for plaque stability in these individuals.

Prognostic value of B-Type natriuretic peptides in patients with stable coronary artery disease: the PEACE Trial.

OBJECTIVES: The purpose of this study was to assess the association between B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the incidence of specific cardiovascular events in low-risk patients with stable coronary disease, the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors, and their ability to identify patients who may benefit from angiotensin-converting enzyme (ACE) inhibition. BACKGROUND: The prognostic value of BNPs in low-risk patients with stable coronary artery disease remains unclear. METHODS: Baseline plasma BNP and NT-proBNP concentrations were measured in 3,761 patients with stable coronary artery disease and preserved left ventricular function participating in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibition) study, a placebo-controlled trial of trandolapril. Multivariable Cox regression was used to assess the association between natriuretic peptide concentrations and the incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke. RESULTS: The BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. In multivariable models, BNP remained associated with increased risk of heart failure, whereas NT-proBNP remained associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP also improved the model for cardiovascular death. The magnitude of effect of ACE inhibition on the likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP baseline concentrations. CONCLUSIONS: In low-risk patients with stable coronary artery disease and preserved ventricular function, BNPs provide strong and incremental prognostic information to traditional risk factors.

No effect of increased water intake on blood viscosity and cardiovascular risk factors.

Observational data have suggested that increased water intake decreases the risk of CHD. A postulated mechanism is that increased water ingestion reduces blood viscosity. The aim of the present study was to assess the effect of increased fluid intake on blood viscosity. Men (n 67) and postmenopausal women (n 27) with one or more risk factors for CVD who reported intake of < or =0.5 litres water daily were randomised to a control group (n 31), an intervention group (n 32) that increased their daily water intake by 1 litre/d and an intervention group (n 31) that ingested 1 litre blueberry juice/d. All were encouraged to continue their usual diet and lifestyle. Whole-blood viscosity and blood and urine chemistries were measured by standard techniques after 2 and 4 weeks. Urine volume increased (by a median of 872 and 725 ml in the water and blueberry juice groups, respectively, v. 10 ml in the control group; P< or =0.002), confirming the subjects' adherence to the protocol. Urine osmolality and urinary levels of Na, K and creatinine decreased in the water and blueberry juice groups v. the controls (P<0.05). No change was seen in whole-blood viscosity or in levels of fibrinogen, total protein, lipids, glucose, insulin, C-peptide or other chemistry and haematology variables. In conclusion, a postulated protective effect of increased water or fluid intake is not explained by a change in blood viscosity and increased fluid intake does not influence CVD risk factors in the short term.

N-terminal pro-B-type natriuretic peptide in risk stratification after acute myocardial infarction in patients on long-term beta-adrenergic receptor blocker therapy.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) appears to be a strong risk marker of mortality in patients with acute coronary syndrome. However, little information is available on NT-proBNP as a predictor of long-term serious cardiovascular events beyond that of left ventricular ejection fraction in patients with acute myocardial infarction (AMI), most of them treated with an early invasive strategy and on a uniform optimal secondary preventive medication including long-term beta-adrenergic receptor blockade. OBJECTIVE: To assess the prognostic impact of plasma NT-proBNP in patients with AMI who received optimal medical treatment including long-term beta-adrenergic receptor blockade. METHODS: Plasma NT-proBNP was measured in 219 patients (age range 31-80 years) with AMI at baseline, and then followed for a median duration of 1.63 years. The first occurrences of a serious cardiovascular event including cardiac mortality, nonfatal MI, and congestive heart failure were registered. RESULTS: Ninety serious cardiovascular events occurred. Left ventricular ejection fraction and reperfusion therapy with thrombolysis or percutaneous coronary intervention were identified as confounders. When adjusting for these factors in multivariate analysis, NT-proBNP was a strong predictor of serious cardiovascular events in patients with a plasma NT-proBNP of >162.2 pmol/l and aged <60 years (p = 0.001). The incidence rate was related to increasing NT-proBNP (p = 0.0017). The risk of serious cardiovascular events was higher in patients with NT-proBNP levels in the highest quartile (> or =162.2 pmol/l) than in those with levels in the three lowest quartiles (rate ratio = 2.5, 95% confidence interval = 1.6-3.9, p = 0.0001). CONCLUSION: AMI patients with high plasma NT-proBNP seem to be at an increased risk of serious cardiovascular events, but only those < or =60 years of age.

The methylenetetrahydrofolate reductase C677T polymorphism is a major determinant of coffee-induced increase of plasma homocysteine: a randomized placebo controlled study.

Some methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are associated with hyperhomocysteinemia. Trials have shown a plasma homocysteine raising effect of coffee. We determined the effect of a daily intake of 600 ml coffee and a supplementation of 200 microg folic acid or placebo on plasma homocysteine (tHcy) with respect to the MTHFR C677T and A1298C polymorphisms. One hundred and twenty healthy, non-smoking men (22%) and women (78%) aged 29-65 years, took part in a controlled, randomized, blinded study with two intervention periods: i) a coffee-free period of three weeks, ii) 600 ml coffee/day and a supplement of 200 microg folic acid/d or placebo for four weeks. The results showed that tHcy at baseline was significantly higher for the 677TT genotype group compared to the 677CC genotype group (p=0.0045) and that this group responded with significantly larger increase in tHcy upon coffee exposure than the 677CC and 677CT genotype groups (p=0.0045 and p=0.0041, respectively). Supplementation with 200 microg folic acid compared to placebo reduced the tHcy increasing effect of coffee in the 677TT genotype group. The A1298C polymorphism did not affect tHcy concentration significantly at any stage in the study. In conclusion, the homocysteine increasing effect of coffee is particularly seen in individuals with the homozygous 677TT genotype. Supplementation with 200 microg folic acid/d decreases this tHcy increment.

Serum homocysteine in relation to mortality and morbidity from coronary heart disease: a 24-year follow-up of the population study of women in Gothenburg.

BACKGROUND: Elevated serum total homocysteine (tHcy) is an established risk factor for cardiovascular disease (CVD), especially in men. However, there are few prospective population studies on female cohorts, and none of these has been longer than 13 years. METHODS AND RESULTS: The Population Study of Women in Gothenburg began in 1968/1969, at which time a representative population-based cohort of women aged 38, 46, 50, 54, and 60 years was recruited. The present cohort is a prospective follow-up of 1368 women in the original cohort for whom blood samples were stored and who were free of previous acute myocardial infarction (AMI) at the 1968/1969 baseline. Homocysteine was analyzed in 2001 with frozen serum from the baseline study and related to AMI incidence and mortality during 24 years of follow-up. Cox regression analyses were used with adjustment for age, traditional risk factors, and tHcy modifiers. For the fifth tHcy quintile, relative risk was 1.86 (95% CI 1.06 to 3.26) for AMI and 5.14 (95% CI 2.22 to 11.92) for death due to AMI. Age-standardized Kaplan-Meier plots for the fifth tHcy quintile versus others showed significant differences both for AMI and for death due to AMI that were apparent after 15 years of follow-up. CONCLUSIONS: Homocysteine in middle-aged women is an independent risk factor for myocardial infarction and in particular mortality due to myocardial infarction. The study illustrates that long-term prospective studies might be necessary to show effects of homocysteine levels on AMI morbidity and mortality in women.