Autoimmune diseases and female-specific cancer risk: A systematic review and meta-analysis.

OBJECTIVES: Among the over 80 different autoimmune diseases, psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) are common representatives. Previous studies indicated a potential link with cancer risk, but suffered often from low statistical power. Thus, we aimed to synthesize the evidence and quantify the association to different female-specific cancer sites. METHODS: The systematic review was performed according to PRISMA guidelines. A search string was developed for the databases PubMed, Web of Science, Cochrane Library and Embase. Results were screened independently by two investigators and the risk of bias was assessed using the ROBINS-E tool. Meta-analyses were performed using inverse variance weighted random-effects models. Statistical between-study heterogeneity was quantified by calculating Cochran's Q, τ2, and Higgins' I2 statistics. Sources of heterogeneity were analyzed and adjusted for within an intensive bias assessment in the form of meta-regression, outlier, influential, and subgroup analyses. A range of methods were used to test and adjust for publication bias. RESULTS: Of 10,096 records that were originally identified by the search strategy, 45 were included in the meta-analyses. RA was inversely associated with both breast and uterine cancer occurrence, while PsO was associated with a higher breast cancer risk. Outlier-adjusted estimates confirmed these findings. Bias assessment revealed differences in geographic regions, particularly in RA patients, with higher estimates among Asian studies. An additional analysis revealed no association between psoriatic arthritis and breast cancer. CONCLUSIONS: RA seems to reduce the risk of breast and uterine cancers, while PsO appears to increase breast cancer risk. Further large studies are required to investigate potential therapy-effects and detailed biological mechanisms.

Depression mediates the association between health literacy and health-related quality of life after myocardial infarction.

Introduction: So far, health literacy (HL) and its related factors in patients with acute myocardial infarction received little attention. Thus, the objective of this study was to investigate the associations between the different dimensions of HL and disease-specific health-related quality of life (HRQOL), and factors that may affect these relations in patients after acute myocardial infarction (AMI). Methods: All survivors of AMI between June 2020 and September 2021, from the Myocardial Infarction Registry Augsburg (n=882) received a postal questionnaire on HL [Health Literacy Questionnaire (HLQ)], HRQOL (MacNew Heart Disease HRQOL questionnaire) and depression (Patient Health Questionnaire). From the 592 respondents, 546 could be included in the analysis. Multivariable linear regression models were performed to investigate the associations between the nine subscales of the HLQ and the total score and three subscales of the MacNew questionnaire. A mediation analysis was performed to estimate direct and indirect effects of HL on HRQOL taking into account the mediating effect of depression. Results: In the sample of 546 patients (72.5% male, mean age 68.5 ± 12.2 years), patients with poor education showed significantly lower HLQ scores. Significant associations between the subscales of the HLQ and the MacNew were found, which remained significant after adjustment for sociodemographic variables with few exceptions. More than 50% of the association between HL and HRQOL was mediated by depression in seven HLQ subscales and a complete mediating effect was found for the HLQ subscales 'Actively managing my health' and 'Appraisal of health information'. Discussion: Depression mediates the associations between HL and disease-specific HRQOL in patients with myocardial infarction.

Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients. / Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos.

BACKGROUND: Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. OBJECTIVE: To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. METHODS: A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. RESULTS: A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. CONCLUSION: High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Health literacy in patients with pulmonary embolism: development and validation of the HeLP (Health Literacy in Pulmonary Embolism)-Questionnaire.

Background: Pulmonary embolism (PE) is a common cardiovascular disease and health literacy is necessary to deal with its consequences after the acute event. The aim of this study was to develop and validate a new questionnaire to measure PE-specific health literacy. Methods: A mixed-methods design with qualitative and quantitative elements was used in the development process. A literature review about health literacy concepts and instruments and interviews with patients with PE and clinicians were conducted. Quantitative analyses included factor analyses, item response theory with a graded partial credit model, and reliability analyses in different test and validation samples. Furthermore, convergent and known-groups validity and responsiveness were assessed. Results: The qualitative results supported a concept of PE-related health literacy with four main topics: dealing with PE-related health information, disease management, health-related selfcare, and social support. An initial item pool of 91 items was developed. Further interviews and an online survey with patients with PE (n = 1,013) were used to reduce the number of items and to confirm structural validity. Confirmatory factor analyses in the final evaluation study with patients with PE (n = 238) indicated a good model fit of the four-factor structure. The Health Literacy in Pulmonary Embolism (HeLP)-Questionnaire showed good reliability (Cronbach's alpha: 0.82 to 0.90). All four subscales were responsive toward receiving a brochure with PE-related health information. Conclusion: The newly developed German HeLP Questionnaire comprises 23 items in four domains and showed good psychometric properties. Further evaluation of the questionnaire in different samples of patients with PE is needed.

Association of post-stroke-depression and health-related quality of life three months after the stroke event. Results from the Stroke Cohort Augsburg (SCHANA) study.

Approximately one-third of patients with stroke show depressive symptoms. The so-called post-stroke depression (PSD) has a negative influence on mortality as well as physical and mental conditions. The aim of this study was to analyse the association between PSD and health-related quality of life (HRQOL) in patients with stroke. The analysis was based on data of 326 patients from the Stroke Cohort Augsburg (SCHANA Study) collected after the stroke event by interview and three months later using a postal survey. Depressive symptoms were measured with the Patient-Health Questionnaire (PHQ-9), subjective health status with the EuroQol 5D visual analogue scale (EQ-5D VAS), and HRQOL with the Stroke Impact Scale (SIS). Patients with depressive symptoms were compared to those without depressive symptoms in terms of sociodemographic characteristics and scores of the SIS and the EQ-5D VAS. Multiple linear regression models were calculated to investigate the association between PSD and subjective health status and HRQOL. Three months after the stroke, 17.8% of patients had depressive symptoms. Patients with PSD showed significantly worse SIS and EQ-5D VAS scores. In addition, an independent negative linear association between PSD and subjective health status and between PSD and all domains of SIS could be found. The study confirmed that PSD is common in patients with mild stroke and negatively related to all stroke-specific HRQOL domains. The results underline the importance of early screening for PSD in stroke patients since it may hinder a successful rehabilitation.

Depression and anxiety up to two years after acute pulmonary embolism: Prevalence and predictors.

INTRODUCTION: Pulmonary embolism (PE) is an acute life-threatening event. Besides known physical long-term consequences such as persistent dyspnoea or reduced physical performance, less attention is given to the emotional experience. METHODS: We used data from patients with PE of the 'Lungenembolie Augsburg (LEA)' cohort study at University Hospital Augsburg. Baseline characteristics were collected during hospital stay and participants received postal questionnaires 3, 6, 12, and 24 months after their PE event. Mental problems were assessed by the Hospital Anxiety and Depression Scale (HADS). Differences in baseline characteristics in patients with or without depression or anxiety at 3 months were tested. Linear mixed models were built to explore long-term effects. RESULTS: About one-in-five of the 297 patients suffered from depressive or anxiety symptoms after PE. Patients with depressiveness 3 months after PE were found to be significantly older, had a higher simplified pulmonary embolism severity index (sPESI), higher education level, more frequently previous depression, lower oxygen saturation, and a longer hospital stay. Linear mixed models revealed significant associations of age, history of depression and sPESI with HADS depression score, and symptoms of dyspnoea with HADS anxiety score after PE. While the association with sPESI decreased over time, persistent dyspnoea and limitations in daily life showed constant associations over the two-year time period for both, depression and anxiety. CONCLUSIONS: The findings highlight depression and anxiety to be common in patients with PE and reveal possible predictors. Careful monitoring the mental health of patients with PE is needed for early detection and intervention.

Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos / Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients

Resumo Fundamento O aumento do peso frequentemente desencadeia mecanismos que elevam a pressão arterial. A obesidade causa mudanças estruturais no miocárdio, incluindo aumento da massa ventricular, dilatação atrial, bem como disfunções diastólicas e sistólicas. Além disso, variações pressóricas nos hipertensos obesos, como a ascensão matinal (AM), podem ter relevância clínica na prevenção dos eventos cardiovasculares. A AM da pressão arterial é um fenômeno fisiológico, que quando elevada pode ser considerada um fator de risco independente para eventos cardiovasculares. Objetivo Avaliar valores da elevação da AM e sua associação com a hipertrofia ventricular esquerda (HVE) e com o Descenso do Sono (DS) em obesos e não obesos hipertensos. Métodos Estudo transversal que avaliou medidas pressóricas à monitorização ambulatorial da pressão arterial (MAPA) e a presença de HVE, avaliada pela ecocardiografia, em 203 pacientes hipertensos em tratamento ambulatorial, separados em dois grupos: 109 não obesos e 94 hipertensos obesos. O nível de significância adotado foi de 0,05 em testes bicaudais. Resultados A AM acima de 20 mmHg à MAPA foi detectada em 59,2% dos pacientes do grupo "não obesos" e em 40,6% no grupo "obesos". A HVE foi encontrada em 18,1% no grupo dos não-obesos e em 39,3% no grupo de obesos, p<0,001. No grupo "obesos" foi observado que AM >16 mmHg esteve associada à HVE, com [razão de prevalência: 2,80; IC95% (1,12-6,98), p=0,03]. Para o grupo dos "não obesos", o ponto de corte da AM para essa associação foi >22 mmHg. Conclusão A AM elevada associou-se positivamente com HVE, com comportamento peculiar na população de hipertensos e obesos.

Abstract Background Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. Objective To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. Methods A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. Results A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. Conclusion High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Efficiency and Safety of Electronic Health Records in Switzerland-A Comparative Analysis of 2 Commercial Systems in Hospitals.

OBJECTIVES: Differences in efficiency and safety between 2 electronic health record (systems A and B) in Swiss hospitals were investigated. METHODS: In a scenario-based usability test under experimental conditions, a total of 100 physicians at 4 hospitals were asked to complete typical routine tasks, like medication or imaging orders. Differences in number of mouse clicks and time-on-task as indicators of efficiency and error type, error count, and rate as indicators of patient safety between hospital sites were analyzed. Time-on-task and clicks were correlated with error count. RESULTS: There were differences in efficiency and safety between hospitals. Overall, physicians working with system B required less clicks (A: 511, B: 442, P = 0.001) and time (A: 2055 seconds, B: 1713 seconds, P = 0.055) and made fewer errors (A: 40%, B: 27%, P < 0.001). No participant completed all tasks correctly. The most frequent error in medication and radiology ordering was a wrong dose and a wrong level, respectively. Time errors were particularly prevalent in laboratory orders. Higher error counts coincided with longer time-on-task (r = 0.50, P < 0.001) and more clicks (r = 0.47, P < 0.001). CONCLUSIONS: The variations in clicks, time, and errors are likely due to naive functionality and design of the systems and differences in their implementation. The high error rates coincide with inefficiency and jeopardize patient safety and produce economic costs and burden on physicians. The results raise usability concerns with potential for severe patient harm. A deeper understanding of differences as well as regulative guidelines and policy making are needed.

The German version of the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire: reliability, responsiveness and structural validity.

PURPOSE: The Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire is the only existing disease-specific instrument for measuring quality of life after pulmonary embolism (PE). It includes six dimensions: frequency of complaints, limitations in activities of daily living, work-related problems, social limitations, intensity of complaints and emotional complaints. The present study aimed to determine the psychometric properties including responsiveness and structural validity of the German version. METHODS: The analysis used data from participants of the LEA cohort study at University Hospital Augsburg. The PEmb-QoL was administered via postal surveys 3, 6 and 12 months post-PE. Internal consistency and test-retest reliability were evaluated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC). Standardized response means (SRM) were calculated for investigating responsiveness. For evaluating the fit of the factor structure, confirmatory factor analysis (CFA) was conducted. RESULTS: Overall, we used data from 299 patients 3 months after PE. Cronbach's alpha (0.87-0.97) and ICC (0.53-0.90) were in an acceptable to good range. SRM scores showed good responsiveness of all dimensions. CFA revealed the four-factor model including one general factor to have a good model fit. CONCLUSION: Despite existing floor effect, most standard criteria of reliability and validity were met and indications for appropriateness of the PEmb-QoL summary score could be found. Apart from some restrictions concerning the factor structure and the dimension of social limitations, our results support the use of the PEmb-QoL questionnaire for evaluating PE-specific quality of life. Future studies should seek replication in different samples to ensure generalizability of the findings.

Evidence-based health information about pulmonary embolism: Assessing the quality, usability and readability of online and offline patient information.

Objective: Pulmonary embolism (PE) is the third most common cardiovascular disease worldwide. However, public awareness is considerably lower than for myocardial infarction or stroke. Patients suffering from PE complain about the lack of (understandable) information and express high informational needs. To uncover if reliable information is indeed scarce, this study evaluates the quantity and quality of existing patient information for tertiary prevention using an evidence-based health information paradigm. Methods: We conducted a quantitative content analysis (n = 21 patient information brochures; n = 67 websites) evaluating content categories addressed, methodical quality, usability, and readability. Results: Results show that there is not enough patient information material focusing on PE as a main topic. Existing patient information material is mostly incomplete, difficult to understand, and low in actionability as well as readability. Conclusion: Our systematic analysis reveals the need for more high-quality patient information on PE as part of effective tertiary prevention. Innovation: This is the first review analyzing content, methodical quality, readability, and usability of patient information on PE. The findings of this analysis are guiding the development of an innovative, evidence-based patient information on PE aiming to support patients' informational needs and their self-care behavior.

Desempenho do eletrocardiograma no diagnóstico da hipertrofia ventricular esquerda em hipertensos idosos e muito idosos / Performance of the electrocardiogram in the diagnosis of left ventricular hypertrophy in older and very older hypertensive patients

Resumo Fundamento: A hipertrofia ventricular esquerda (HVE) é um importante fator de risco cardiovascular, independente da hipertensão arterial. Apesar da evolução dos exames de imagem, o eletrocardiograma (ECG) ainda é o mais utilizado na avaliação inicial, porém, com baixa sensibilidade. Objetivo: Avaliar o desempenho dos principais critérios eletrocardiográficos para HVE em indivíduos hipertensos idosos e muito idosos. Métodos: Em coorte de hipertensos foram realizados ECGs e EcoDopplercardiogramas (ECO), e separados em três grupos etários: <60 anos, Grupo I; 60-79 anos Grupo II; e ≥80 anos, Grupo III. Os critérios eletrocardiográficos mais utilizados foram aplicados para o diagnóstico da HVE: Perúgia; Peguero-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duração; Cornell voltagem; Cornell voltagem duração; Sokolow-Lyon voltagem; R de aVL ≥11 mm; RaVL duração. Na avaliação do desempenho desses critérios, além da sensibilidade (Sen) e especificidade (Esp), foram analisadas as "Odds Ratios diagnóstico" (DOR). Consideramos p-valor <0,05 para as análises, com testes bi-caudais. Resultados: Em 2.458 pacientes, a HVE estava presente pelo ECO em 781 (31,7%). Nos Grupos I e II, os melhores desempenhos foram para os critérios de Narita, Perúgia, (Rm+Sm) x duração, sem diferenças estatísticas entre eles. No Grupo III (muito idosos) os critérios de Perúgia e (Rm+Sm) x duração tiveram os melhores desempenhos: Perúgia [44,7/89,3; (Sen/Esp)] e (Rm+Sm) duração [39,4%/91,3%; (Sen/Esp), p<0,05)], com os melhores resultados de DOR:6,8. Isto sugere que nessa população de muito idosos esses critérios têm maior poder discriminatório para separar pacientes com HVE. Conclusão: Nos hipertensos muito idosos os critérios eletrocardiográficos de Perúgia e (Rm+Sm) x duração apresentaram os melhores desempenhos diagnósticos para HVE.

Abstract Background: Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, regardless of arterial hypertension. Despite the evolution of imaging tests, the electrocardiogram (ECG) is still the most used in the initial evaluation, however, with low sensitivity. Objective: To evaluate the performance of the main electrocardiographic criteria for LVH in elderly and very elderly hypertensive individuals. Methods: In a cohort of hypertensive patients, ECGs and doppler echocardiographies (ECHO) were performed and separated into three age groups: <60 years, Group I; 60-79 years Group II; and ≥80 years, Group III. The most used electrocardiographic criteria were applied for the diagnosis of LVH: Perugia; Pegaro-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duration; Cornell voltage; Cornell voltage duration; Sokolow-Lyon voltage; R of aVL ≥11 mm; RaVL duration. In evaluating the performance of these criteria, in addition to sensitivity (Sen) and specificity (Esp), the "Diagnostic Odds Ratios" (DOR) were analyzed. We considered p-value <0.05 for the analyses, with two-tailed tests. Results: In 2,458 patients, LVH was present by ECHO in 781 (31.7%). In Groups I and II, the best performances were for the criteria of Narita, Perugia, (Rm+Sm) x duration, with no statistical differences between them. In Group III (very elderly) the Perugia criteria and (Rm+Sm) x duration had the best performances: Perugia [44,7/89.3; (Sen/Esp)] and (Rm+Sm) duration [39.4%/91.3%; (Sen/Esp), p<0.05)], with the best PAIN results:6.8. This suggests that in this very elderly population, these criteria have greater discriminatory power to separate patients with LVH. Conclusion: In very elderly hypertensive patients, the Perugia electrocardiographic criteria and (Rm+Sm) x duration showed the best diagnostic performance for LVH.

Quality standards for safe medication in nursing homes: development through a multistep approach including a Delphi consensus study.

OBJECTIVES: The aim of the study was to develop quality standards reflecting minimal requirements for safe medication processes in nursing homes. DESIGN: In a first step, relevant key topics for safe medication processes were deducted from a systematic search for similar guidelines, prior work and discussions with experts. In a second step, the essential requirements for each key topic were specified and substantiated with a literature-based rationale. Subsequently, the requirements were evaluated with a piloted, two-round Delphi study. SETTING: Nursing homes in Switzerland. PARTICIPANTS: Interprofessional panel of 25 experts from science and practice. PRIMARY AND SECONDARY OUTCOME MEASURES: Each requirement was rated for its relevance for a safer and resident-oriented medication on a 9-point Likert-Scale based on the RAND/UCLA method. The requirements were considered relevant if, in the second round, the median relevance rating was ≥7 and the proportion of ratings ≥7 was ≥80%. RESULTS: Five key topics with a total of 87 requirements were elaborated and rated in the Delphi study. After the second round (response rate in both rounds 100%), 85 requirements fulfilled the predefined criteria and were therefore included in the final set of quality standards. The five key topics are: (I) 'The medication is reviewed regularly and in defined situations', (II) 'The medication is reviewed in a structured manner', (III) 'The medication is monitored in a structured manner', (IV) 'All healthcare professionals are committed to an optimal interprofessional collaboration' and (V) 'Residents are actively involved in medication process'. CONCLUSIONS: We developed normative quality standards for a safer and resident-oriented medication in Swiss nursing homes. Altogether, 85 requirements define the medication processes and the behaviour of healthcare professionals. A rigorous implementation may support nursing homes in taking a step towards safer and resident-oriented medication.

Performance of the Electrocardiogram in the Diagnosis of Left Ventricular Hypertrophy in Older and Very Older Hypertensive Patients. / Desempenho do Eletrocardiograma no Diagnóstico da Hipertrofia Ventricular Esquerda em Hipertensos Idosos e Muito Idosos.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, regardless of arterial hypertension. Despite the evolution of imaging tests, the electrocardiogram (ECG) is still the most used in the initial evaluation, however, with low sensitivity. OBJECTIVE: To evaluate the performance of the main electrocardiographic criteria for LVH in elderly and very elderly hypertensive individuals. METHODS: In a cohort of hypertensive patients, ECGs and doppler echocardiographies (ECHO) were performed and separated into three age groups: <60 years, Group I; 60-79 years Group II; and ≥80 years, Group III. The most used electrocardiographic criteria were applied for the diagnosis of LVH: Perugia; Pegaro-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duration; Cornell voltage; Cornell voltage duration; Sokolow-Lyon voltage; R of aVL ≥11 mm; RaVL duration. In evaluating the performance of these criteria, in addition to sensitivity (Sen) and specificity (Esp), the "Diagnostic Odds Ratios" (DOR) were analyzed. We considered p-value <0.05 for the analyses, with two-tailed tests. RESULTS: In 2,458 patients, LVH was present by ECHO in 781 (31.7%). In Groups I and II, the best performances were for the criteria of Narita, Perugia, (Rm+Sm) x duration, with no statistical differences between them. In Group III (very elderly) the Perugia criteria and (Rm+Sm) x duration had the best performances: Perugia [44,7/89.3; (Sen/Esp)] and (Rm+Sm) duration [39.4%/91.3%; (Sen/Esp), p<0.05)], with the best PAIN results:6.8. This suggests that in this very elderly population, these criteria have greater discriminatory power to separate patients with LVH. CONCLUSION: In very elderly hypertensive patients, the Perugia electrocardiographic criteria and (Rm+Sm) x duration showed the best diagnostic performance for LVH.

FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) é um importante fator de risco cardiovascular, independente da hipertensão arterial. Apesar da evolução dos exames de imagem, o eletrocardiograma (ECG) ainda é o mais utilizado na avaliação inicial, porém, com baixa sensibilidade. OBJETIVO: Avaliar o desempenho dos principais critérios eletrocardiográficos para HVE em indivíduos hipertensos idosos e muito idosos. MÉTODOS: Em coorte de hipertensos foram realizados ECGs e EcoDopplercardiogramas (ECO), e separados em três grupos etários: <60 anos, Grupo I; 60-79 anos Grupo II; e ≥80 anos, Grupo III. Os critérios eletrocardiográficos mais utilizados foram aplicados para o diagnóstico da HVE: Perúgia; Peguero-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duração; Cornell voltagem; Cornell voltagem duração; Sokolow-Lyon voltagem; R de aVL ≥11 mm; RaVL duração. Na avaliação do desempenho desses critérios, além da sensibilidade (Sen) e especificidade (Esp), foram analisadas as "Odds Ratios diagnóstico" (DOR). Consideramos p-valor <0,05 para as análises, com testes bi-caudais. RESULTADOS: Em 2.458 pacientes, a HVE estava presente pelo ECO em 781 (31,7%). Nos Grupos I e II, os melhores desempenhos foram para os critérios de Narita, Perúgia, (Rm+Sm) x duração, sem diferenças estatísticas entre eles. No Grupo III (muito idosos) os critérios de Perúgia e (Rm+Sm) x duração tiveram os melhores desempenhos: Perúgia [44,7/89,3; (Sen/Esp)] e (Rm+Sm) duração [39,4%/91,3%; (Sen/Esp), p<0,05)], com os melhores resultados de DOR:6,8. Isto sugere que nessa população de muito idosos esses critérios têm maior poder discriminatório para separar pacientes com HVE. CONCLUSÃO: Nos hipertensos muito idosos os critérios eletrocardiográficos de Perúgia e (Rm+Sm) x duração apresentaram os melhores desempenhos diagnósticos para HVE.

Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease.

BACKGROUND: Metabolic syndrome (MS) is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. OBJECTIVES: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS). METHODS: Patients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. RESULTS: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078). CONCLUSIONS: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease / Associação de Múltiplas Variantes Genéticas com a Extensão e Gravidade da Doença Coronária

Abstract Background: Metabolic syndrome (MS) is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS). Methods: Patients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078). Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

Resumo Fundamento: A síndrome metabólica (SM) é condição que, associada à doença coronária e a eventos cardiovasculares, pode ser influenciada por variantes genéticas, determinando maior gravidade da aterosclerose coronária. Objetivos: Avaliar a contribuição de polimorfismos genéticos para a extensão da doença coronária em indivíduos com SM e recente síndrome coronária aguda (SCA). Métodos: Pacientes (n = 116, 68% homens) com 56 (9) anos e critérios para SM foram prospectivamente selecionados no período de hospitalização após uma SCA. Parâmetros clínicos e laboratoriais, proteína C-reativa ultrassensível, substâncias reativas ao ácido tiobarbitúrico, adiponectina, função endothelial e o escore de Gensini foram analisados. Os polimorfismos da paraoxonase-1 (PON-1), metilenotetrahidrofolato redutase (MTHFR), óxido nítrico sintase endotelial (ENOS), enzima conversora da angiotensina (ECA), receptor tipo 1 da angiotensina II (AT1R), apolipoproteína C3 (APOC3), lipoproteína lipase (LPL) foram analisados por reação em cadeia da polimerase (PCR) seguida da identificação dos polimorfismos no comprimento do fragmento de restrição (RFLP), criando-se um escore genético. Testes paramétricos e não-paramétricos foram utilizados, conforme apropriado, com p < 0,05 considerado como significativo. Resultados: Os polimorfismos da PON-1, MTHFR e ENOS não estavam em equilíbrio de Hardy-Weinberg. O genótipo DD da LPL associou-se com lesões coronarianas mais graves e extensas. O escore genético tendeu a ser maior nos pacientes com escore de Gensini < P50 (13,7 ± 1,5 vs. 13,0 ± 1,6, p = 0,066), com correlação inversa entre o escore genético e o de Gensini (R = -0,194, p = 0,078). Conclusões: O polimorfismo da LPL associou-se à maior gravidade da doença coronária em pacientes com SM e SCA. Combinação de polimorfismos genéticos associou-se à extensão da doença coronariana, sendo a doença mais grave quanto menor o escore genético.

Estudos dos polimorfismos do sistema renina-angiotensina em afrodescendentes hipertensos tratados / Study of renin-angiotensin aldosterone system polymorphisms in treated hypertensive African descendents

A hipertensão arterial (HA) é um dos principais fatores de risco para a morbimortalidade cardiovascular. Os polimorfismos do sistema renina-angiotensina-aldosterona (SRAA) estão envolvidos na fisiopatologia da HA. Estudos mostram que afrodescendentes tendem a ser hipertensos com taxa mais alta de complicações. Este estudo teve por objetivo avaliar a prevalência dos polimorfismos do SRAA - da enzima conversora de angiotensina (ECA I/D), do antagonista do receptor da angiotensina II (AT1R A/C1166) e da aldosterona sintase (CYP11B2-344T/C) - em pacientes hipertensos afrodescendentes em tratamento. Vinte e três pacientes hipertensos afrodescendentes foram avaliados clinicamente (pressão arterial - PA e índice de massa corporal - IMC), laboratorialmente (perfil lipídico, creatinina e glicemia) e foram analisados os polimorfismos da ECA, AT1R e CYP por PCR. Os dados obtidos foram comparados com os de 21 hipertensos não afrodescendentes. Não houve diferença significativa na PA, IMC e perfil metabólico entre os grupos. Entretanto, o estudo dos polimorfismos do SRAA revelou diferenças significativas na distribuição dos genótipos (grupo I afro e II não afro): a frequência para os genes da ECA foi 47,8% DD, 43,5% DI e 8,7% I vs. 14,3% DD, 47,6% DI e 38,1% II (p=0,0017); para genes do AT1R: 100% AA, 0% AC e 0% CC no I vs. 33,3,% AA, 22,2% AC e 44,4% CC no II (p <0,0001); e, para o gene CYP11B2: 56% TT, 21,7% TC e 4,3% CC no I vs. 33% TT, 77,7% TC e 5,5% CC no II (p=0,034) entre os afrodescendentes e controles, respectivamente. Os resultados sugerem diferenças genéticas entre os pacientes hipertensos afrodescendentes no grupo estudado.

Efeitos da terapia combinada atorvastatina e clopidogrel na biodisponibilidade da estatina e na função plaquetária em pacientes com doença coronária estável / Effects of the artovastatin and clopidogrel combination therapy on station bioavailability and platelet function of patients with stable coronary disease

Introdução: Atorvastatina 80 mg é recomendada a pacientes portadores de doença coronária para redução de eventos cardiovasculares, havendo controvérsia sobre as interações farmacocinéticas entre doses elevadas das estatinas e uso concomitante de clopidogrel, por compartilharem a mesma via de biotransformação. Este estudo avaliou os efeitos da terapia combinada atorvastatina/clopidogrel na farmacocinética da estatina e função plaquetária em pacientes com doença coronária estável, sob uso crônico e efetivo de estatina. Método: Os pacientes foram admitidos quatro vezes para internação (V1 a V4) em leito-dia. Sete dias (D) antes da primeira internação a estatina em uso foi suspensa. A seguir, receberam atorvastatina 80 mg (D1 a D22) e clopidogrel 75 mg/dia (D8 a D29). Em todas as V foram obtidas amostras de sangue em jejum para dosagens lipídicas, avaliação da função plaquetária (técnica da placa e cone) e quantificação dos níveis plasmáticos de atorvastatina (cromatografia líquida e espectrometria de massa). Resultados: A suspensão por uma semana da estatina modificou o perfil lipídico (P < 0,05 vs. basal), ocorrendo rápida melhora de todas as frações lipídicas após atorvastatina 80 mg (P < 0,005; V1 > V2, V3 e V4). A adesão plaquetária foi menor com clopidogrel isolado (P = 0,003; V4 < V1, V2 e V3), enquanto para a agregação houve menor valor com tratamento combinado atorvastatina/clopidogrel ou clopidogrel isolado comparado aos demais períodos (P < 0,0001; V3 e V4 < V1 e V2). O clopidogrel não modificou as concentrações de atorvastatina. Conclusão: Atorvastatina em alta dose não afetou as meias respostas plaquetárias ao clopidogrel; entretanto, curto período de suspensão da estatina piorou o perfil lipídico e a função plaquetária.

Background: Atorvastatin 80 mg is recommended in patientswith coronary artery disease to reduce cardiovascular events, however, there is controversy regarding the pharmacokinetic interactions between high doses of statins and the concomitant use of clopidogrel, since they share the same biotransformation pathway. This study evaluated theeffects of the atorvastatin/clopidogrel combination therapy on the pharmacokinetics of statins and on platelet function of patients with stable coronary artery disease receivingchronic statins. Method: Patients were admitted four times (V1 to V4) to a day-clinic. Statin was discontinued sevendays (D) before the first admission. Patients then received atorvastatin 80 mg (D1 to D22) and clopidogrel 75 mg/day (D8 to D29). Fasting blood samples were obtained at all time points for lipid measurements, platelet function tests (cone and plate technique), and quantification of atorvastatin plasma levels (liquid chromatography and mass spectrometry). Results: The discontinuation of statins for one weekchanged the lipid profile (P < 0.05 vs. baseline), with an early improvement of all lipid parameters after the administration of atorvastatin 80 mg (P < 0.005; V1 > V2, V3 and V4). Platelet adhesion was lower with clopidogrel alone (P = 0.003; V4 < V1, V2 and V3), whereas platelet aggregation values were lower following the atorvastatin/clopidogrel combination therapy or clopidogrel alone when compared to the other time points (P < 0.0001; V3 and V4 < V1 and V2). The use of clopidogrel did not affect atorvastatin serum levels. Conclusion: High-dose atorvastatin did not affectplatelet responses to clopidogrel, however the short-term statindiscontinuation worsened the lipid profile and platelet function.

Early increase in autoantibodies against human oxidized low-density lipoprotein in hypertensive patients after blood pressure control.

BACKGROUND: Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of antihypertensive therapeutic regimens. METHODS: Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of antihypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS: Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS: We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.

High circulating autoantibodies against human oxidized low-density lipoprotein are related to stable and lower titers to unstable clinical situation.

BACKGROUND: Oxidized lipoproteins and antibodies anti-oxidized low-density lipoprotein (anti-oxLDL) have been detected in human plasma and in atherosclerotic lesions. However, the role of these autoantibodies in the maintenance of vascular health or in the pathogenesis of acute vascular insults remains unclear. We examined the relationship of human immunoglobulin G (IgG) anti-oxLDL antibodies with cardiovascular disease risk markers in stable subjects and in patients after an acute coronary syndrome (ACS). METHODS: Titers of human anti-oxLDL antibodies were measured in hypertensive subjects in primary prevention (n=94), without other risk factors, and in individuals after a recent ACS event who also had metabolic syndrome (n=116). Autoantibodies against copper ion oxidized LDL were measured by enzyme-linked-immunosorbent assay. RESULTS: Anti-oxLDL titers were higher in hypertensive patients and these subjects presented lower high sensitivity C-reactive protein (hs-CRP) than those with ACS (p<0.0001). We found significant correlations between anti-oxLDL and hs-CRP (r=-0.284), body mass index (r=-0.256), waist circumference (r=-0.368), apolipoprotein B (r=-0.191), glucose (r=-0.303), systolic blood pressure (r=0.319), diastolic blood pressure (r=0.167), high-density lipoprotein cholesterol (r=0.224) and apolipoprotein A1 (r=0.257) (p<0.02 for all). After multiple linear regression hs-CRP, fasting glucose and waist circumference remained independently and inversely associated with anti-oxLDL. CONCLUSIONS: Acute inflammatory and metabolic conditions decrease titers of human antibodies of IgG class against oxidized LDL, and that circulating anti-oxLDL antibodies could be associated with a protective role in atherosclerosis.

Early glucometabolic profile in patients with acute coronary syndromes and metabolic syndrome.

BACKGROUND: Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE: This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS: A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (DeltaI30/DeltaG30). RESULTS: Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION: High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.