Comparison of office, home and ambulatory blood pressure measurements in hypertensive and suspected hypertensive SWICOS participants.

PURPOSE: Hypertension should be confirmed with the use of home BP measurement (HBPM) or 24h ambulatory BP measurement (ABPM). The aim of our study was to compare measurements obtained by OBPM, HBPM and ABPM in individuals with elevated OBPM participating in the population-based Swiss Longitudinal Cohort Study (SWICOS). MATERIAL AND METHODS: Participants with OBPM ≥140/90 mmHg assessed their BP using HBPM and ABPM. The cut-off for hypertension was ≥135/85 mmHg for HBPM, ≥130/80 mmHg for ABPM. White-coat hypertension (WCH) was defined as normal HPBM and ABPM in participants not taking antihypertensive drugs. Uncontrolled hypertension was defined as hypertension in HBPM or ABPM despite antihypertensive treatment. RESULTS: Of 72 hypertensive subjects with office BP ≥140/90 mmHg and valid measurements of HBPM and ABPM, 39 were males (aged 62.8 ± 11.8y), 33 were females (aged 57.4 ± 14.2y). Hypertension was confirmed with HBPM and ABPM in 17 participants (24%), with ABPM only in 24 further participants (33%), and with HBPM only in 2 further participants (3%). Participants who had hypertension according to ABPM but not HBPM were younger (59 ± 11 y versus 67 ± 16 y; p < 0.001) and more frequently still working (83% versus 23%; p < 0.001). The prevalence of WCH was 28%. Among the 32 subjects taking antihypertensive drugs, uncontrolled hypertension was found in 49%. CONCLUSION: This population-based study found a high prevalence of WCH and potential uncontrolled hypertension among individuals with elevated OBPM. This study, therefore, supports the ESH recommendations of complementing OBPM by ABPM or HBPM. The use of HBPM instead of ABPM for the confirmation of hypertension in individuals with elevated OBPM might lead to underdiagnosis and uncontrolled hypertension, in particular in the younger working population. In these individuals, this study suggests using ABPM instead of HBPM.

What is already known?Comparing blood pressure measurements in the doctor's office or clinic (OBPM) with out-of-office measurements (either self-measurement at home (HBPM) or ambulatory over 24 hours during both day and night times (ABPM)) improves the accuracy of hypertension diagnosis.Why was the study done?This study was done to provide additional information by comparing HBPM and ABPM in individuals with elevated OPBMs (≥140/≥90mmHg), who participated in the Swiss Longitudinal Cohort Study (SWICOS)What was found?Our study confirmed differences between office and out-of-office measurements. In 60% of the study participants, ABPM or HBPM confirmed the elevated OBPM but only around half of these participants were treated with antihypertensive drugs. A high proportion of the participants (28%) had white coat hypertension.What does this study add?Our study adds to the literature already available on this issue by reporting on data obtained from a cohort of individuals living in a countryside area of Southern Switzerland.This study also showed that HBPM might underestimate BP in the younger working population.How might this impact on clinical practice?The findings of this population-based study support the European Society of Hypertension recommendations for wider use of out-of-office blood pressure measurement for the confirmation of hypertension in individuals with elevated OBPM to avoid underdiagnosis and uncontrolled hypertension.In the young working population, ABPM should be used instead of only HBPM to confirm hypertension.

Trigeminal cardiac reflex: new thinking model about the definition based on a literature review.

Trigeminocardiac reflex (TCR) is a brainstem reflex that manifests as sudden onset of hemodynamic perturbation in blood pressure (MABP) and heart rate (HR), as apnea and as gastric hypermotility during stimulation of any branches of the trigeminal nerve. The molecular and clinical knowledge about the TCR is in a constant growth since 1999, what implies a current need of a review about its definition in this changing context. Relevant literature was identified through searching in PubMed (MEDLINE) and Google scholar database for the terms TCR, oculocardiac reflex, diving reflex, vasovagale response. The definition of the TCR varies in clinical as well as in research studies. The main difference applies the required change of MABP and sometimes also HR, which most varies between 10% and 20%. Due to this definition problem, we defined, related to actual literature, 2 major (plausibility, reversibility) and 2 minor criteria (repetition, prevention) for a more proper identification of the TCR in a clinical or research setting. Latest research implies that there is a need for a more extended classification with 2 additional subgroups, considering also the diving reflex and the brainstem reflex. In this review, we highlighted criteria for proper definition and classification of the TCR in the light of increased knowledge and present a thinking model to overcome this complexity. Further we separately discussed the role of HR and MABP and their variation in this context. As another subtopic we gave attention to is the chronic TCR; a variant that is rarely seen in clinical medicine.

A magnetic force sensor on a catheter tip for minimally invasive surgery.

This paper presents a magnetically guided catheter for minimally invasive surgery (MIS) with a magnetic force sensing tip. The force sensing element utilizes a magnetic Hall sensor and a miniature permanent magnet mounted on a flexible encapsulation acting as the sensing membrane. It is capable of high sensitivity and robust force measurements suitable for in-vivo applications. A second larger magnet placed on the catheter allows the catheter to be guided by applying magnetic fields. Precise orientation control can be achieved with an external magnetic manipulation system. The proposed device can be used in many applications of minimally invasive surgery (MIS) to detect forces applied on tissue during procedures or to characterize different types of tissue for diagnosis.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

T-cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells in vitro and is associated with malignant transformation of cutaneous SCC in vivo.

BACKGROUND: Cadherins play important roles in controlling keratinocyte growth, differentiation and survival. Atypical glycosylphosphatidylinositol-anchored T-cadherin (T-cad) is highly expressed in the basal keratinocyte layer of skin. The role of T-cad in keratinocyte biology and pathology is unclear. OBJECTIVES: To define the role of T-cad in the pathogenesis of cutaneous squamous cell carcinoma (SCC) through gain-of-function and loss-of-function studies in vitro and through examination of T-cad expression patterns in human cutaneous SCC specimens in relation to histological classification of degree of tumour differentiation. METHODS: In vitro studies employed lentiviral-mediated overexpression/silencing of T-cad in normal human keratinocyte (HaCaT) and SCC (A431) cell lines, monolayer and multicellular spheroid culture models, cell morphology analyses and assays of random motility and invasion. Immunohistochemistry was performed on skin specimens from patients with actinic keratosis, Bowen disease or SCC. RESULTS: In vitro, silencing of T-cad induced a morphologically elongated and disorganized cell phenotype, increased random motility and markedly enhanced invasive potential. Overexpression of T-cad induced a morphologically spread and compact cell phenotype and blunted invasive potential. In vivo, regional loss of T-cad expression was more frequent and prominent in SCC classified as moderately-to-poorly differentiated than in SCC classified as well differentiated. However, in both categories aberrant and/or absence of T-cad expression was associated with histological features of a potentially more malignant and invasive phenotype of cutaneous SCC. CONCLUSIONS: T-cad is a controlling determinant of SCC phenotype and invasive behaviour and its loss is associated with the process of malignant transformation from noninvasive to invasive SCC.

Is pretreatment with Beta-blockers beneficial in patients with acute coronary syndrome?

OBJECTIVES: The role of beta-blockers in the treatment of hypertension is discussed controversially and the data showing a clear benefit in acute coronary syndromes (ACS) were obtained in the thrombolysis era. The goal of this study was to analyze the role of pretreatment with beta-blockers in patients with ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) registry, we analyzed outcomes of patients with beta-blocker pretreatment in whom they were continued during hospitalization (group A), those without beta-blocker pretreatment but with administration after admission (group B) and those who never received them (group C). Major adverse cardiac events defined as composed endpoint of re-infarction and stroke (during hospitalization) and/or in-hospital death were compared between the groups. RESULTS: A total of 24,709 patients were included in the study (6,234 in group A, 12,344 in group B, 6,131 in group C). Patients of group B were younger compared to patients of group A and C (62.5, 67.6 and 68.4, respectively). In the multivariate analysis, odds ratio for major adverse cardiac events was 0.59 (CI 0.47-0.74) for group A and 0.66 (CI 0.55-0.83) for group B, while group C was taken as a reference. CONCLUSIONS: beta-Blocker therapy is beneficial in ACS and they should be started in those who are not pretreated and continued in stable patients who had been on chronic beta-blocker therapy before.

Simple point-of-care risk stratification in acute coronary syndromes: the AMIS model.

BACKGROUND: Early risk stratification is important in the management of patients with acute coronary syndromes (ACS). OBJECTIVE: To develop a rapidly available risk stratification tool for use in all ACS. DESIGN AND METHODS: Application of modern data mining and machine learning algorithms to a derivation cohort of 7520 ACS patients included in the AMIS (Acute Myocardial Infarction in Switzerland)-Plus registry between 2001 and 2005; prospective model testing in two validation cohorts. RESULTS: The most accurate prediction of in-hospital mortality was achieved with the "Averaged One-Dependence Estimators" (AODE) algorithm, with input of seven variables available at first patient contact: age, Killip class, systolic blood pressure, heart rate, pre-hospital cardiopulmonary resuscitation, history of heart failure, history of cerebrovascular disease. The c-statistic for the derivation cohort (0.875) was essentially maintained in important subgroups, and calibration over five risk categories, ranging from <1% to >30% predicted mortality, was accurate. Results were validated prospectively against an independent AMIS-Plus cohort (n = 2854, c-statistic 0.868) and the Krakow-Region ACS Registry (n = 2635, c-statistic 0.842). The AMIS model significantly outperformed established "point-of-care" risk-prediction tools in both validation cohorts. In comparison to a logistic regression-based model, the AODE-based model proved to be more robust when tested on the Krakow validation cohort (c-statistic 0.842 vs 0.746). Accuracy of the AMIS model prediction was maintained at 12-month follow-up in an independent cohort (n = 1972, c-statistic 0.877). CONCLUSIONS: The AMIS model is a reproducibly accurate point-of-care risk stratification tool for the complete range of ACS, based on variables available at first patient contact.

Beyond auscultation--acoustic cardiography in the diagnosis and assessment of cardiac disease.

Auscultation has long been an important part of the evaluation of patients with known and suspected cardiac disease. The subsequent development of phonocardiography provided an analogue visual display that permitted a more detailed analysis of the timing and acoustical characteristics of heart sounds, murmurs, clicks and rubs. In addition, the measurement of systolic time intervals enabled a valuable non-invasive assessment of left ventricular function. Acoustic cardiography, a much more recently developed technology, has enabled the simultaneous acquisition of ECG and cardiac acoustical data. This user-friendly and cost-effective technology permits acquisition of detailed information regarding systolic and diastolic left ventricular function and provides both a computerized interpretation and a visual display of the findings. Its clinical applications include the evaluation of patients with suspected heart failure, ischaemia and cardiac arrhythmias and the optimization of cardiovascular drug and device therapies. It can also be used in a wide variety of ambulatory and inpatient monitoring applications.

S100A1 deficiency results in prolonged ventricular repolarization in response to sympathetic activation.

S100A1 is a Ca(2+)-binding protein and predominantly expressed in the heart. We have generated a mouse line of S100A1 deficiency by gene trap mutagenesis to investigate the impact of S100A1 ablation on heart function. Electrocardiogram recordings revealed that after beta-adrenergic stimulation S100A1-deficient mice had prolonged QT, QTc and ST intervals and intraventricular conduction disturbances reminiscent of 2 : 1 bundle branch block. In order to identify genes affected by the loss of S100A1, we profiled the mutant and wild type cardiac transcriptomes by gene array analysis. The expression of several genes functioning to the electrical activity of the heart were found to be significantly altered. Although the default prediction would be that mRNA and protein levels are highly correlated, comprehensive immunoblot analyses of salient up- or down-regulated candidate genes of any cellular network revealed no significant changes on protein level. Taken together, we found that S100A1 deficiency results in cardiac repolarization delay and alternating ventricular conduction defects in response to sympathetic activation accompanied by a significantly different transcriptional regulation.

Serum procalcitonin has the potential to identify Staphylococcus aureus endocarditis.

The role of procalcitonin (PCT) in the diagnosis of infective endocarditis (IE) remains unclear. The aim of our study was to test the accuracy of PCT in the early diagnosis of IE and analyse if the accuracy of PCT is dependent on the type of pathogen causing IE. We carried out a prospective analysis of hospitalised patients referred for transthoracic echocardiography to search for an IE. The plasma PCT value was measured at the time of echocardiography. The diagnosis of IE was made using the modified Duke criteria. A total of 77 patients were included. IE was confirmed in 15 patients. The mean PCT values were 6.9 (+/-21.6) ug/l in patients without IE and 6.4 (+/-11.7) ug/l in patients with confirmed IE (p=0.92). IE patients with Staphylococcus aureus bacteraemia (n=7) had significantly higher PCT values compared to IE patients with other types of bacteraemia (n=8) (13.1 vs. 0.435, p=0.0299). This study demonstrates that PCT levels markedly differ at the time when IE is diagnosed. While PCT values are very high in patients with S. aureus bacteraemia, they are surprisingly low in patients with Streptococcus viridans bacteraemia, which are common offenders of endocarditis. We conclude that serum PCT has the potential to be used in the early diagnosis of S. aureus endocarditis.

Is transesophageal echocardiography still necessary to exclude patent foramen ovale?

OBJECTIVES: Current guidelines still recommend transesophageal echocardiography (TEE) as reference method to diagnose interatrial shunts. The aim was to test the accuracy of high-end transthoracal echocardiography (TTE) to exclude inter-atrial shunts. METHODS: Prospective TTE and TEE study with second harmonic imaging to determine left-to-right shunt (L/R) by both colour Doppler or R/L by contrast echocardiography in patients with unexplained cerebrovascular incidents or newly detected valvular or myocardial disease. RESULTS: An inter-atrial shunt was diagnosed in 200 of 438 analyzed patients (117 males). Colour Doppler echocardiography visualized a shunt in 67 patients (34%) on TTE vs. 84 (42%) patients on TEE (p <0.0001). However injection of agitated blood with a valsalva maneuver detected 190 (95%) interatrial shunts by both TTE and TEE, but 10 shunts (5%) only by TTE. CONCLUSIONS: Our study shows that patent foramen ovale can safely be demonstrated with high-end transthoracic contrast- echocardiography. If additional studies confirm our results, TTE has the potential to become the method of choice in the diagnosis of PFO.

Pt(x)Ru(1-x)/Ru(0001) surface alloys-formation and atom distribution.

The formation of PtRu surface alloys by deposition of submonolayer Pt films on a Ru(0001) substrate and subsequent annealing to about 1350 K and the distribution of the Pt atoms in the surface layer were investigated by scanning tunneling microscopy. Quantitative statistical analysis reveals (i) negligible losses of Pt into subsurface regions up to coverages close below 1 monolayer, (ii) a homogeneous distribution of the Pt atoms over the surface, and (iii) the absence of a distinct long-range or short-range order in the surface layer. In addition, the density of specific adsorption ensembles is analyzed as a function of Pt surface content. Possible conclusions on the process for surface alloy formation are discussed. The results are compared with the properties of PtRu bulk alloys and the findings in previous adsorption studies on similar surface alloys (H. Rauscher, T. Hager, T. Diemant, H. Hoster, F. Bautier de Mongeot and R. J. Behm, Surf. Sci., 2007, 601, 4608; T. Diemant, H Rauscher and R. J. Behm, J. Phys. Chem. C, in press).

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring.

Approximate entropy (ApEn) of blood pressure (BP) can be easily measured based on software analysing 24-h ambulatory BP monitoring (ABPM), but the clinical value of this measure is unknown. In a prospective study we investigated whether ApEn of BP predicts, in addition to average and variability of BP, the risk of hypertensive crisis. In 57 patients with known hypertension we measured ApEn, average and variability of systolic and diastolic BP based on 24-h ABPM. Eight of these fifty-seven patients developed hypertensive crisis during follow-up (mean follow-up duration 726 days). In bivariate regression analysis, ApEn of systolic BP (P<0.01), average of systolic BP (P=0.02) and average of diastolic BP (P=0.03) were significant predictors of hypertensive crisis. The incidence rate ratio of hypertensive crisis was 14.0 (95% confidence interval (CI) 1.8, 631.5; P<0.01) for high ApEn of systolic BP as compared to low values. In multivariable regression analysis, ApEn of systolic (P=0.01) and average of diastolic BP (P<0.01) were independent predictors of hypertensive crisis. A combination of these two measures had a positive predictive value of 75%, and a negative predictive value of 91%, respectively. ApEn, combined with other measures of 24-h ABPM, is a potentially powerful predictor of hypertensive crisis. If confirmed in independent samples, these findings have major clinical implications since measures predicting the risk of hypertensive crisis define patients requiring intensive follow-up and intensified therapy.

The impact of statin treatment on presentation mode and early outcomes in acute coronary syndromes.

OBJECTIVES: The role of statin use in the treatment of acute coronary syndromes (ACS) is not clear. The aim of our study was to evaluate the role of statins in ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) Project, we compared the effects of chronic statin use, statin therapy after admission and no statin therapy on presentation mode and outcomes in ACS. RESULTS: Available data from the period 2001-2006 including 11,603 patients were analyzed. Major cardiac event rates and in-hospital mortality were more common in statin-naive patients compared to patients who received statins. CONCLUSIONS: Our results support the importance of statin treatment in ACS. Chronic statin therapy seems to alter the initial presentation of ACS but it is questionable whether it provides an additional effect on early outcomes compared to the establishment of statin therapy after admission in statin-naive patients.