Framingham score and microalbuminuria: combined future targets for primary prevention?

BACKGROUND: Risk assessment is the cornerstone of primary prevention of cardiovascular disease. Our objective was to evaluate the prognostic value of the Framingham score in microalbuminuric subjects without a history of cardiovascular disease and whether this risk score can predict the benefit of treatment with fosinopril or pravastatin. METHODS: Subjects were randomized to fosinopril 20 mg or matching placebo, and to pravastatin 40 mg or matching placebo (mean age 51 +/- 12 years, 65% men, N = 830). Prediction of 10-year risk for coronary heart disease by the Framingham score was performed using the risk factor categories with LDL cholesterol. RESULTS: Albuminuria was correlated with Framingham score at baseline (P < 0.001). In the population with a Framingham risk score <20%, both albuminuria and Framingham risk score were independent predictors of the primary end point. A two-fold increase of albuminuria or the Framingham risk score was associated with a hazard ratio of 1.60 (95% CI 1.10-2.31), P = 0.013 and 3.00 (95% CI 1.40-6.44), P = 0.005, respectively. In contrast to fosinopril, pravastatin showed a significant beneficial effect on Framingham risk score after 4 years of follow-up (P < 0.001). Furthermore, the observed absolute risk reduction in cardiovascular events was greater than calculated by the Framingham risk score. CONCLUSION: The Framingham score is useful in microalbuminuric subjects as a prognostic tool. In addition, when considering the risk score as a target of intervention, the beneficial effects of therapies might be underestimated. Combining the Framingham score with the level of urinary albumin excretion is suggested as a primary prevention strategy with higher efficiency.     

Assessing the prognostic value of coronary endothelial function in patients referred for a first coronary angiogram

At present, the value of endothelial function as a prognostic tool has been evaluated only in selected groups of patients with mild or minor coronary artery disease, not in the complete spectrum of patients presenting with angina. The objective of this study was to evaluate whether endothelium-dependent vasodilation of the coronary arteries in response to acetylcholine infusion as a marker of endothelial function would have prognostic value in patients referred for a first coronary angiogram. The data suggest that endothelial function assessment does not contribute to the prediction of outcomes in patients referred for a first coronary angiogram.     

Distinct methylation profiles of glioma subtypes

Gliomas are tumors of the central nervous system with a wide spectrum of different tumor types. They range from pilocytic astrocytoma, with a generally good prognosis, to the extremely aggressive malignant glioblastoma. In addition to these 2 types of contrasting neoplasms, several other subtypes can be distinguished, each characterized by specific phenotypic, as well as genotypic features. Recently, the epigenotype, as evident from differentially methylated DNA loci, has been proposed to be useful as a further criterion to distinguish between tumor types. In our study, we screened 139 tissue samples, including 33 pilocytic astrocytomas, 46 astrocytomas of different grades, 7 oligoastrocytomas, 10 oligodendrogliomas, 10 glioblastoma multiforme samples and 33 control tissues, for methylation at CpG islands of 15 different gene loci. We used the semiquantitative high throughput method MethyLight to analyze a gene panel comprising ARF, CDKN2B, RB1, APC, CDH1, ESR1, GSTP1, TGFBR2, THBS1, TIMP3, PTGS2, CTNNB1, CALCA, MYOD1 and HIC1. Seven of these loci showed tumor specific methylation changes. We found tissue as well as grade specific methylation profiles. Interestingly, pilocytic astrocytomas showed no evidence of CpG island hypermethylation, but were significantly hypomethylated, relative to control tissues, at MYOD1. Our results show that glioma subtypes have characteristic methylation profiles and, with the exception of pilocytic astrocytomas, show both locus specific hyper- as well as hypomethylation.     

Molecular evidence of Pneumocystis transmission in pediatric transplant unit

We describe an outbreak of Pneumocystis jirovecii pneumonia in a pediatric renal transplant unit, likely attributable to patient-to-patient transmission. Single-strand conformation polymorphism molecular typing showed that 3 affected patients had acquired the same 2 strains of Pneumocystis, which suggests interhuman infection. An infant with mitochondriopathy was the probable index patient.     

Self-reported chemical sensitivity in Germany: a population-based survey

OBJECTIVES: Environmental clinics are frequented by patients with fears and complaints related to environmental triggers. A dose-independent overreaction to small doses of widely used and generally non-toxic chemicals is referred to as multiple chemical sensitivity (MCS), but no clearly defined clinical syndrome with objective physical findings has been delineated so far. We aimed to obtain information about symptoms, supposed environmental triggers, the frequency of self-reported chemical sensitivity, and of the diagnosis MCS in Germany. METHODS: We conducted a representative survey among 2032 adult Germans. RESULTS: We found self-reported chemical sensitivity in 9% and physician-diagnosed MCS in 0.5% of our representative sample. Physical complaints were common in the whole study population and in chemically sensitive individuals, but there was no clear-cut symptom constellation among the latter. The most common complaints were headache, fatigue, sleep disturbances, joint pain, mood changes and nervousness. A subjective connection between complaints and environmental triggers was denied by 67% of the whole group and by 35% of the self-reported chemically sensitive. Factor analysis of environmental triggers suggested that a specific exposure situation rather than chemical similarity is the basis for individual trigger combinations. CONCLUSIONS: The prevalence of subjective sensitivity towards chemicals is similar to such rates reported from other countries. There is a relatively low awareness of the MCS-concept, and it appears to be diagnosed less frequently than, e.g., in the USA. Since symptoms and triggers in chemically sensitive individuals did not differ from the general population, our data do not suggest the existence of a widespread new syndrome related to chemical sensitivities in Germany. We outline the limitations of self-reported chemical sensitivity as the major criterion for such a contentious diagnosis as MCS.     

Determination of vessel size: a putative framework to assess clinical outcome

BACKGROUND: Unknown is the predictive value of the coronary artery diameter without the administration of vasomotor stimuli. A small reference diameter of the target vessel has been demonstrated to be an adverse prognostic factor in patients undergoing revascularisation. The present study investigated the prognostic value of the proximal non-stenotic left anterior descending coronary artery (LAD) diameter in patients referred for a first diagnostic angiogram without a previous revascularisation. METHODS: A total of 277 patients (mean age 57 year, 61% male) were eligible for analysis. The proximal non-stenotic diameter of the LAD was measured by quantitative coronary angiography without prior nitrate infusion. We defined a small LAD as a diameter < or =2.5 mm. Cardiovascular events were defined as cardiac death, myocardial infarction, and hospitalizations for unstable angina. RESULTS: During a median follow-up of 47 months, 24 major cardiac events occurred. The cumulative survival for patients with a small LAD was significantly lower, than for patients with a large LAD (hazard ratio 2.51; 95% confidence interval 1.11-5.66, p=0.03). In the multivariate analysis, a LAD diameter < or =2.5 mm remained a significant predictor of cardiovascular events after adjustment for age, gender, and the presence of significant coronary artery disease (hazard ratio 2.32; 95% confidence interval 1.01-5.34, p=0.048). CONCLUSION: In patients referred for a first diagnostic angiogram without a previous revascularisation, the diameter of the proximal non-stenotic LAD is an independent predictor of cardiovascular events.     

The impact of duration of untreated psychosis and premorbid functioning on outcome of first inpatient treatment in schizophrenic and schizoaffective patients

OBJECTIVE: The aim of the study was to investigate the association between the duration of untreated psychosis, premorbid functioning and outcome from first inpatient treatment in schizophrenic or schizoaffective patients. METHOD: The data of 196 first-hospitalized patients with a schizophrenic or schizoaffective disorder according to the ICD-10 criteria were analyzed using univariate and multivariate methods. Patients' characteristics were prospectively assessed using standardized instruments at the time of first admission and discharge. RESULTS: The analyses revealed that a duration of untreated psychosis longer than 12 months was independently and significantly associated with a poorer outcome from first inpatient treatment. Premorbid functioning might have an additional influence on outcome, but this influence seems to be dependent on the diagnostic category. CONCLUSIONS: The findings suggest that the duration of untreated psychosis is an independent prognostic factor for the outcome in schizophrenic and schizoaffective disorders.