Zoltán Vokó

Risk score for predicting death, myocardial infarction, and stroke in patients with stable angina, based on a large randomised trial cohort of patients

Abstract Objective To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function. Design Multivariate Cox regression analysis of data from a large multicentre trial. Setting Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand. Participants 7311 patients with all required data available. Main outcome measure Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years. Results 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure ≥ 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients. Conclusion This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.

A comparative health survey of the inhabitants of Roma settlements in Hungary.

OBJECTIVES We compared the health of people living in Roma settlements with that of the general population in Hungary. METHODS We performed comparative health interview surveys in 2003 to 2004 in representative samples of the Hungarian population and inhabitants of Roma settlements. RESULTS In persons older than 44 years, 10% more of those living in Roma settlements reported their health as bad or very bad than did those in the lowest income quartile of the general population. Of those who used any health services, 35% of the Roma inhabitants and 4.4% of the general population experienced some discrimination. In Roma settlements, the proportion of persons who thought that they could do much for their own health was 13% to 15% lower, and heavy smoking and unhealthy diet were 1.5 to 3 times more prevalent, than in the lowest income quartile of the general population. CONCLUSIONS People living in Roma settlements experience severe social exclusion, which profoundly affects their health. Besides tackling the socioeconomic roots of the poor health of Roma people, specific public health interventions, including health education and health promotion programs, are needed.

Dietary antioxidants and the risk of ischemic stroke: the Rotterdam Study.

In the Rotterdam Study, the authors investigated whether high intake of antioxidants from food is associated with the risk of stroke. Among 5,197 participants who were followed on average for 6.4 years, 227 ischemic strokes occurred. Higher intake of antioxidants was associated with a lower risk of stroke. The relationship was dose-dependent, significant for vitamin C, and most pronounced in smokers. These results agree with the view that high dietary intake of antioxidants, in particular vitamin C and—in smokers—vitamin E, reduces the risk of stroke.

Excess Stroke Among Hypertensive Men and Women Attributable to Undertreatment of Hypertension

Background and Purpose —Most population-based studies indicate that a considerable proportion of hypertensive subjects are undertreated and that undertreatment is more prevalent among hypertensive men than among hypertensive women. The aim of our study was to investigate the consequences of undertreatment of hypertension for women and men in terms of stroke occurrence. Methods —Approximately 45 000 men and women aged ≥20 years were examined in 2 population-based studies in the Netherlands. A cohort of 2616 hypertensive subjects (pharmacologically treated hypertensives and untreated hypertensives who needed pharmacological treatment according to the severity of their hypertension and the coexistence of additional cardiovascular risk factors) was selected for a follow-up study. Follow-up (mean duration, 4.6 years) was complete for 2369 (91%) of the enrolled hypertensive subjects. Results —Compared with treated and controlled hypertensives, the relative risks of stroke for treated and uncontrolled hypertensives and for untreated hypertensives who needed treatment were 1.30 (95% CI, 0.70 to 2.44) and 1.76 (95% CI, 1.05 to 2.94), respectively. These relative risks and the prevalence of (undertreated) hypertension in the total population of 45 000 subjects were used to estimate the number of strokes in the Netherlands attributable to undertreatment. Among hypertensive men and women aged ≥20 years in the Netherlands, the proportions of strokes attributable to treated but uncontrolled blood pressure were 3.1% (95% CI, −5.2% to 18.7%) and 4.1% (95% CI, −7.2% to 20.7%), respectively. For untreated hypertensive men and women who should have been treated, these proportions were 22.8% (95% CI, 0.8% to 38.4%) and 25.4% (95% CI, 0.5% to 42.5%), respectively. Conclusions —Increasing the detection of hypertension and improving adherence to current guidelines might prevent a considerable proportion of the incident strokes among hypertensives. The potential impact of achieving control of blood pressure in patients already being treated on the reduction of strokes requires further investigation.

Does socioeconomic status fully mediate the effect of ethnicity on the health of Roma people in Hungary

Background: Several models have been proposed to explain the association between ethnicity and health. It was investigated whether the association between Roma ethnicity and health is fully mediated by socioeconomic status in Hungary. Methods: Comparative health interview surveys were performed in 2003–04 on representative samples of the Hungarian population and inhabitants of Roma settlements. Logistic regression models were applied to study whether the relationship between Roma ethnicity and health is fully mediated by socioeconomic status, and whether Roma ethnicity modifies the association between socioeconomic status and health. Results: The health status of people living in Roma settlements was poorer than that of the general population (odds ratio of severe functional limitation after adjustment for age and gender 1.8 (95% confidence interval 1.4 to 2.3)). The difference in self-reported health and in functionality was fully explained by the socioeconomic status. The less healthy behaviours of people living in Roma settlements was also related very strongly to their socioeconomic status, but remained significantly different from the general population when differences in the socioeconomic status were taken into account, (eg odds ratio of daily smoking 1.6 (95% confidence interval 1.3 to 2.0) after adjustment for age, gender, education, income and employment). Conclusion: Socioeconomic status is a strong determinant of health of people living in Roma settlements in Hungary. It fully explains their worse health status but only partially determines their less healthy behaviours. Efforts to improve the health of Roma people should include a focus on socioeconomic status, but it is important to note that cultural differences must be taken into account in developing public health interventions.

EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis

Copy number alterations of the epidermal growth factor receptor (EGFR) gene have been extensively analyzed in different cancers, but no data are available for primary malignant melanoma. The aim of the present study was to simultaneously investigate the EGFR gene and chromosome 7 copy number alterations in 81 cutaneous malignant melanomas by interphase FISH and correlate the data with clinicopathological parameters of patients. EGFR mRNA levels were detected by Affymetrix GeneChip Human Genome U133 Plus 2.0 expression arrays for 16 lesions. Both increased gene dosage and chromosome 7 alterations were found in 70% of tumors. Extra EGFR copies were detected in an additional 10% of samples. Polysomy 7 was associated with EGFR gene amplification. Significant correlation was found between EGFR alterations and histological subtypes, tumor thickness, ulceration and metastases formation. Amplification was significantly higher in lesions that developed metastases within 2 years after surgical excision of the primary tumor. Gene copy alterations were associated with elevated mRNA expression in 77% of lesions when compared to tumors with disomic EGFR status, the correlation was not directly proportional to gene copy number. Associations between protein expression and mRNA levels were even less prominent. In conclusion, our study indicates that amplification of the EGFR gene and polysomy 7 are frequent alterations in primary melanomas and are associated with bad prognosis. Further studies are required to clarify whether melanoma patients with EGFR alterations can benefit from anti‐EGFR therapy.

Factor XIII Val34Leu variant protects against coronary artery disease - A meta-analysis

Several studies suggested that Val34Leu variant of factor XIII (FXIII) might have a protective effect against coronary artery disease (CAD), but studies not supporting these findings have also been published. The authors performed a meta-analysis of 16 studies on 5,346 cases and 7,053 controls that investigated the association between Val34Leu polymorphism and CAD defined as history of myocardial infarction or significant stenosis on a coronary artery assessed by coronary angiography. Because of the heterogeneity of the study-specific results, the pooled effect estimates were calculated by a random-effects empirical Bayes model. The combined odds ratios for CAD were 0.82 (95% confidence interval [95% CI] 0.73, 0.94) for the heterozygotes of the FXIIIVal34Leu variant, 0.89 (95% CI 0.69, 1.13) for the homozygotes, and 0.81 (95% CI 0.70, 0.92) for the heterozygotes and homozygotes combined. The results were essentially the same when only myocardial infarction was considered as outcome. The beneficial effect of the polymorphism might be smaller than the effect estimates obtained in this meta-analysis, because the analysis raised the possibility of publication bias. Data published in the literature suggest that gene-gene and gene-environmental interactions might significantly influence the protective effect of FXIII-A Val34Leu polymorphism.

A systematic review of the health-related quality of life and economic burdens of anorexia nervosa, bulimia nervosa, and binge eating disorder

PurposeTo perform a systematic review of the health-related quality of life (HRQoL) and economic burdens of anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED).MethodsA systematic literature search of English-language studies was performed in Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier, and Cochrane Library. Cost data were converted to 2014 Euro.ResultsSixty-nine studies were included. Data on HRQoL were reported in 41 studies (18 for AN, 17 for BN, and 18 for BED), on healthcare utilization in 20 studies (14 for AN, 12 for BN, and 8 for BED), and on healthcare costs in 17 studies (9 for AN, 11 for BN, and only 2 for BED). Patients’ HRQoL was significantly worse with AN, BN, and BED compared with healthy populations. AN, BN, and BED were associated with a high rate of hospitalization, outpatient care, and emergency department visits. However, patients rarely received specific treatment for their eating disorder. The annual healthcare costs for AN, BN, and BED were €2993 to €55,270, €888 to €18,823, and €1762 to €2902, respectively.ConclusionsAN, BN, and BED have a serious impact on patient’s HRQoL and are also associated with increased healthcare utilization and healthcare costs. The burden of BED should be examined separately from that of BN. The limited evidence suggests that further research is warranted to better understand the differences in long-term HRQoL and economic burdens of AN, BN, and BED.

Genetic, physiological, and lifestyle predictors of mortality in the general population

OBJECTIVES We investigated the quality of 162 variables, focusing on the contribution of genetic markers, used solely or in combination with other characteristics, when predicting mortality. METHODS In 5974 participants from the Rotterdam Study, followed for a median of 15.1 years, 7 groups of factors including age and gender, genetics, socioeconomics, lifestyle, physiological characteristics, prevalent diseases, and indicators of general health were related to all-cause mortality. Genetic variables were identified from 8 genome-wide association scans (n = 19,033) and literature review. RESULTS We observed 3174 deaths during follow-up. The fully adjusted model (C-statistic for 15-year follow-up [C15y] = 0.80; 95% confidence interval [CI] = 0.79, 0.81) predicted mortality well [corrected]. Most of the additional information apart from age and sex stemmed from physiological markers, prevalent diseases, and general health. Socioeconomic factors and lifestyle contributed meaningfully to mortality risk prediction with longer prediction horizon. Although specific genetic factors were independently associated with mortality, jointly they contributed little to mortality prediction (C(15y) = 0.56; 95% CI = 0.55, 0.57). CONCLUSIONS Mortality can be predicted reasonably well over a long period. Genetic factors independently predict mortality, but only modestly more than other risk indicators.

Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4

The inflammatory mediators, cytokines and complement proteins are believed to regulate the sequential events during the development of lesions secondary to ischaemia and reperfusion. The endothelial cell monolayer of the brain microvasculature is the critical interface between the blood-borne mediators and brain tissue. The involvement of these cells in complement production and regulation has not been well documented. In the present study, expression of complement proteins (C1 inhibitor, factor H, factor B, C4) by cultured endothelial cells obtained from human brain microvessels has been characterized. Interferon gamma upregulates the production of all the complement factors studied. Serine proteases, plasmin and miniplasmin induce the expression of C4, decrease the level of ELISA detectable C1 inhibitor, and do not affect the production of factors H and B. These data indicate that complement proteins are expressed locally by the brain microvessels, and may modulate the inflammatory responses of brain tissue.