Lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients in non-metropolitan areas of Brandenburg, Germany.

Background and aims: In the non-metropolitan region of Brandenburg (Germany), which is characterized by high rates of cardiovascular diseases and underserved medical care, there is a lack of awareness regarding lipoprotein(a) [Lp(a)] as a risk factor. In addition, data from patients with atherosclerotic cardiovascular disease (ASCVD) in diverse regional backgrounds, including the understudied Brandenburg cohort, and various healthcare statuses remain insufficient. Methods: In this WalkByLab study, Lp(a) levels were monitored in a non-metropolitan cohort (n = 850) in Brandenburg, Germany, comprising 533 patients at high cardiovascular risk and 317 healthy controls. Patients underwent a comprehensive angiological screening, which included blood serum analysis, assessment of medical and family history, cardiovascular risk, and disease status, and evaluation of lifestyle and quality of life. All parameters were evaluated with regard to two groups based on Lp(a) levels: low (<50 mg/dl) and high (≥50 mg/dl). Results: Brandenburg patients with cardiovascular diseases showed higher Lp(a) levels than healthy controls (24.2% vs. 14.8%, p = 0.001). Logistic regression analysis with different characteristics revealed that Lp(a) was an independent risk factor significantly associated with ASCVD (OR 2.26, 95% CI 1.32-3.95, p = 0.003). The high-Lp(a) group showed a higher proportion of patients with coronary artery disease, peripheral artery disease, or cerebrovascular disease compared to the low-Lp(a) group (50% vs. 36.8%; 57.7% vs. 45.8%; 17.6% vs. 9.2%; p = 0.004); also, a higher percentage of patients in the high-Lp(a) group had heart failure (72.8% vs. 53.2%, p = 0.014) and myocardial infarction (24.7% vs. 13.9%, p = 0.001). The high-Lp(a) group exhibited higher rates of statins (63.1% vs. 50.4%, p = 0.003), ezetimibe (14.8% vs. 5.5.%, p = 0.001), and beta-blockers (55.7% vs. 40.7%, p = 0.001) use. Lp(a) levels were found to be independent of physical activity or smoking behavior and did not change over time (12 months). Conclusions: Our study highlights the significance of elevated Lp(a) levels in Brandenburg cardiovascular patients and identifies them as an independent risk factor for ASCVD, which has implications for addressing cardiovascular health of non-metropolitan populations.

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease.

Background: We investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD). Methods: In total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis. Results: cf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P < 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (ß = 0.229, P = 0.002) and leu-mtDNA (ß = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (ß = -0.426, P < 0.0001). Conclusion: TL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.

Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease.

BACKGROUND: The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice. METHODS: Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants' plasma. Treadmill testing with Gardner protocol was used to evaluate participants' walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance. RESULTS: A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients' PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity. CONCLUSIONS: Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.

Effect of ACEI and ARB treatment on nitric oxide-dependent endothelial function.

Background: Angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are widely used as a first-line therapy for the treatment of cardiovascular disease. Here, ACEI modulate the bradykinin receptor (BDKRB1 and BDKRB2) system and NO-dependent endothelial function, thus determining cardiovascular health and regenerative arteriogenesis. The current study aims at evaluating nitric oxide-dependent endothelial function, and gene expression of bradykinin receptors in peripheral blood mononuclear cells (PBMC) from patients with ACEI or ARB treatment. Patients and methods: The WalkByLab has been established to screen cardiovascular patients for peripheral artery disease and coronary artery disease. In total 177 patients from WalkByLab with heterogenous disease and risk status were randomly selected, divided according to their medication history into the following groups: 1. ACEI group, 2. ARB group or 3. non-ACE/ARB group. Total plasma nitrite/nitrate (NO) levels were measured, endothelial function was evaluated by assessing flow meditated dilation (FMD). PBMC were isolated from peripheral whole blood, and gene expression (qRT-PCR) of bradykinin receptors and angiotensin converting enzyme were assessed. Results: Plasma total NO concentration in the ACEI group (24.66±16.28, µmol/l) was increased as compared to the ARB group (18.57±11.58, µmol/l, P=0.0046) and non-ACE/ARB group (16.83±8.64, µmol/l, P=0.0127) in patients between 40 to 90 years of age. However, FMD values (%) in the ACEI group (7.07±2.40, %) were similar as compared to the ARB (6.35±2.13, %) and non-ACE/ARB group (6.51±2.15, %), but significantly negatively correlated with age. Interestingly, BDKRB1 mRNA level was significantly higher and BDKRB2 mRNA level lower in the ACEI group (BDKRB1 3.88-fold±1.05, BDKRB2 0.22-fold±0.04) as compared to the non-ACE/ARB group (BDKRB1 1.00-fold±0.39, P<0.0001, BDKRB2 1.00-fold±0.45, P=0.0136). Conclusions: ACEI treatment enhances total nitrite/nitrate concentration, furthermore, upregulates BDKRB1 in PBMC, but downregulates BDKRB2 mRNA expression. FMD is a strong determinant of vascular aging and is sensitive to underlying heterogenous cardiovascular diseases.

Risk Factor Management in Non-Metropolitan Patients with Coronary and Peripheral Artery Disease - A Protocol of a Prospective, Multi-Center, Quality Improvement Strategy.

INTRODUCTION: Coronary artery disease (CAD) and peripheral arterial disease (PAD) account for significant morbidity and mortality in Germany and are more prevalent in rural, non-metropolitan areas. The goal of this study is to screen patients for their current atherosclerotic status, initiate treatment according to the latest scientific findings using a standardised multimodal approach and track their atherosclerotic status over one year. METHODS AND ANALYSIS: This manuscript describes the study protocol of a prospective, multicentre registry of 500 sequential patients with CAD and/or PAD in rural, non-metropolitan regions of Germany. Patients, who visit the "WalkByLab" at the Brandenburg Medical School, Brandenburg, Germany, will be assessed by using our structured, multimodal risk factor management (SMART) tool to evaluate cardiovascular morbidity data, collect information on care and deliver multimodal therapy. The study's primary objective is a cross-sectional examination of the risk profile, diagnostic and therapeutic status in this patient group. Secondary objectives include the assessment of risk factor correlations as well as changes in risk-factor profile and therapy adherence. Patients will be examined at baseline and followed up at three-monthly intervals for one year. Over this time, atherosclerotic risk factors and patient adherence to defined therapeutic strategies will be evaluated. Study completion is estimated to be December 2021. An expansion of this concept into other rural, non-metropolitan neighbouring regions is planned. ETHICS AND DISSEMINATION: This registry was assessed and approved by the ethics committee of the Brandenburg State Medical Association, Brandenburg, Germany, and conducted in accordance with the Declaration of Helsinki. The study findings will be disseminated through usual academic channels including meeting presentations and peer-reviewed publications. PROTOCOL VERSION: 1.0.

Real-world clinical performance of commercial SARS-CoV-2 rapid antigen tests in suspected COVID-19: A systematic meta-analysis of available data as of November 20, 2020.

OBJECTIVES: Rapid antigen tests, or RATs, are a type of lateral flow chromatographic immunoassay utilized to aid the diagnosis of SARS-CoV-2 infection. We performed a systematic meta-analysis to compare the real-world performance of commercially available RATs. METHODS: We searched several databases and websites for manufacturer-independent prospective clinical performance studies comparing SARS-CoV-2 RATs and RT-PCR. Only studies on RATs that did not need a separate reader for result retrieval and that reported data on viral load, patients' symptom status, sample type, and PCR assay used were included. RESULTS: 19 studies utilizing 11,109 samples with 2,509 RT-PCR-positives were included. RAT sensitivity varied between 28.9% (95% CI 16.4-44.3) and 98.3% (95% CI 91.1-99.7), likely dependent upon population characteristics, viral load, and symptom status. RAT specificity varied between 92.4% (95% CI 87.4-95.9) and 100% (95% CI 99.7-100) with one outlier. The RATs by Roche Diagnostics/SD Biosensor and Abbott had the highest pooled sensitivity (82.4% [95% CI 74.2-88.4] and 76.9% [95% CI 72.1-81.2], respectively). Sensitivity in high-viral-load samples (cycle threshold ≤25) showed heterogeneity among the different RATs. CONCLUSION: The RATs offered by Roche Diagnostics/SD Biosensor and Abbott provide sufficient manufacturer-independent, real-world performance data to support their use to detect current SARS-CoV-2 infection, particularly in high-viral-load populations.

Preulcerous Risk Situation in Diabetic Foot Syndrome: Proposal for a Simple Ulcer Prevention Score.

BACKGROUND: Preulcerous risk situations in patients with diabetes are often undiagnosed and care administered too late. Even with regular medical check-ups and status documentation, foot examinations have not been given enough attention. Diagnosing an individual patients' risk of developing diabetic foot ulcers may increase vigilance for diabetic foot syndrome (DFS), and the appropriate prevention measures matching the risk involved may prevent the emergence of diabetic ulcers. The classical DFS risk factors are well established and have been extensively covered in the literature; however, there is a lack of efficient screening tools that could be used for a rapid assessment of diabetic foot ulcer risk. METHODS: A methodical literature search was conducted to assess relevant publications for the preparation of a simple risk score for amputation related to diabetic foot ulcer. We then analyzed the risk factors for predictive value as odds ratios in foot ulcers and/or amputation. We used the available data to deduce a mean value to reflect the authors' consensus. RESULTS: In view of the current literature on the matter, we have developed a semi-quantitative scoring system using just a few items to allow rapid and visual risk assessment for diabetic foot ulcers alongside recommendations for prevention and a sensible follow-up strategy to match the risk. CONCLUSION: This relatively simple score enables rapid risk classification for patients that can ease the way for both physicians and patients in gaining an insight into individual risk situations. The score provides more effective preventative measures for high-risk patients against future complications.

Clinical performance evaluation of a SARS-CoV-2 Rapid Antibody Test for determining past exposure to SARS-CoV-2.

OBJECTIVES: Due to the number of asymptomatic infections and limited access to high-performance antibody tests, the true prevalence and seropositivity of SARS-CoV-2 infection remains unknown. To fill this gap, the clinical performance of a point-of-care SARS-CoV-2 Rapid Antibody Assay, a chromatographic immunoassay for detecting IgM/IgG antibodies, in near patient settings was assessed. METHODS: Forty-two anti-SARS-Cov-2 positive (CoV+) and 92 anti-SARS-Cov-2 negative (CoV-) leftover samples from before December 2019 were assessed; the Elecsys® Anti-SARS-CoV-2 was used as the reference assay. Analytical specificity was tested using leftover samples collected before December 2019 from patients with common cold symptoms. RESULTS: The SARS-CoV-2 Rapid Antibody Test was 100.0% (95% CI 91.59-100.0) sensitive and 96.74% (95% CI 90.77-99.32) specific, with 0.00% assay failure rate. No cross-reactivity was observed against the common cold panel. Method comparison was additionally conducted by two external laboratories, using 100 CoV+ and 275 CoV- samples, also comparing whole blood versus plasma matrix. The comparison demonstrated 96.00% positive and 96.36% negative percent agreement for plasma with the Elecsys Anti-SARS-CoV-2 and 99.20% percent overall agreement between whole blood and EDTA plasma. CONCLUSION: The SARS-CoV-2 Rapid Antibody Test demonstrated similar performance to the manufacturer's data and a centralised automated immunoassay, with no cross-reactivity with common cold panels.

German guideline on the diagnosis and treatment of peripheral artery disease - a comprehensive update 2016.

The prevalence of peripheral artery disease (PAD) is increasing worldwide and is strongly age-related, affecting about 20 % of Germans over 70 years of age. Recent advances in endovascular and surgical techniques as well as clinical study results on comparative treatment methods strengthened the need for a comprehensive review of the published evidence for diagnosis, management, and prevention of PAD. The interdisciplinary guideline exclusively covers distal aorta and atherosclerotic lower extremity artery disease. A systematic literature review and formal consensus finding process, including delegated members of 22 medical societies and two patient self-support organisations were conducted and supervised by the Association of Scientific Medical Societies in Germany, AWMF. Three levels of recommendation were defined, A = "is recommended/indicated", B = "should be considered", C = "may be considered", means agreement of expert opinions due to lack of evidence. Altogether 294 articles, including 34 systematic reviews and 98 RCTs have been analysed. The key diagnostic tools and treatment basics have been defined. In patients with intermittent claudication endovascular and/or surgical techniques are treatment options depending on appropriate individual morphology and patient preference. In critical limb ischaemia, revascularisation without delay by means of the most appropriate technique is key. If possible and reasonable, endovascular procedures should be applied first. The TASC classification is no longer recommended as the base of therapeutic decision process due to advances in endovascular techniques and new crural therapeutic options. Limited new data on rehabilitation and follow-up therapies have been integrated. The article summarises major new aspects of PAD treatment from the updated German Guidelines for Diagnosis and Treatment of PAD. Limited scientific evidence still calls for randomised clinical trials to close the present gap of evidence.

CMR First-Pass Perfusion for Suspected Inducible Myocardial Ischemia.

Cardiovascular magnetic resonance (CMR) has evolved from a pioneering research tool to an established noninvasive imaging method for detecting inducible myocardial perfusion deficits. In this consensus document, experts of different imaging techniques summarize the existing body of evidence regarding CMR perfusion as a viable complement to other established noninvasive tools for the assessment of perfusion and discuss the advantages and pitfalls of the technique. A rapid, standardized CMR perfusion protocol is described, which is safe, clinically feasible, and cost-effective for centers with contemporary magnetic resonance equipment. CMR perfusion can be recommended as a routine diagnostic tool to identify inducible myocardial ischemia.

Prevalence of deep vein thrombosis in acutely admitted ambulatory non-surgical intensive care unit patients.

BACKGROUND: Data on prevalence rates of venous thromboembolism (VTE) in different patient populations are scarce. Most studies on this topic focus on older patients or patients with malignancies, immobilization or thrombophilia. Less is known about the VTE risk profile of non-surgical patients presenting with a variety of medical diseases of differing severity. Aim of the present study was to investigate VTE prevalence in a pospective cohort study of ambulatory medical intensive care unit patients within 24 h after acute admission. METHODS: Prospective cohort study of 102 consecutive patients after acute admission to medical intensive care unit. Ultrasound compression sonography, APACHE-II-Scoring and laboratory examination was performed within 24 hours after admission.Possible determinants of a high risk of VTE were examined. In all patients with a confirmed diagnosis of DVT or suspicion of PE thoracic computer tomography (CT) was performed. RESULTS: VTE was found in 7.8% out of 102 of patients, mean APACHE-II-Score was 14 (mortality risk of about 15%). Thrombus location was femoropopliteal in 5 patients, iliacal in 2 and peroneal in 1 patient. Five VTE patients had concomitant PE (62.5% of VTE, 4.9% of all patients). No predictors of prevalent VTE were identified from univariable regression analysis although relative risk was high in patients with a history of smoking (RR 3.40), immobility (RR 2.50), and elevated D-Dimer levels (RR 3.49). CONCLUSIONS: Prevalent VTE and concomitant PE were frequent in acutely admitted ICU patients.

Clinical impact of patient adherence to a fixed-dose combination of olmesartan, amlodipine and hydrochlorothiazide.

BACKGROUND AND OBJECTIVES: Recent findings from randomized clinical trials indicate an improved patient adherence and blood pressure (BP) control by using fixed-dose combinations (FDCs) in the treatment of hypertension. The aim of the present study was to verify those data in a large real-world sample of hypertensive patients and to cross-check adherence evaluation performed by physicians and patients self-assessment. METHODS: A European multi-center, prospective, 24-week, non-interventional study was conducted including 14,979 patients with essential hypertension and new treatment with olmesartan, amlodipine and hydrochlorothiazide as an FDC. Patients' adherence was measured using the Morisky Medication Adherence Scale (MMAS-8) and a non-standardized questionnaire was used by physicians and patients for self-assessment. RESULTS: The mean age of the patients was 63.9±11.78 years and 46.5% were women. One or more cardiovascular risk factors were present in 71.9% of patients and 94.7% had been treated for hypertension before study entry. Mean adherence to medication by MMAS-8 improved from 6.0 to 6.9 at study end. Corresponding improvements of adherence were seen on physicians' and patients' self-assessments throughout the study. Mean decrease of systolic/diastolic BP was 26.4/12.8 mmHg without a relevant difference between the MMAS-8 adherence levels. BP target achievement improved from 55.3 to 67.7% in patients with low versus high adherence. The overall rate of patients with adverse drug reactions was very low (1.76%) but more frequent in patients with low adherence. CONCLUSIONS: Our data confirm previous clinical trial data on the improvement of medication adherence by switching antihypertensive combination therapy to an FDC and a subsequent improvement in BP target achievement. An observed trend toward a reduction in adverse drug reactions needs to be further investigated in clinical trials.

Prevalence and control of high blood pressure in primary care: results from the German Metabolic and Cardiovascular Risk Study (GEMCAS).

Contemporary epidemiological data on blood pressure readings, hypertension prevalence and control in unselected patient populations covering a broad age range are scarce. The aim here is to report the prevalence of high blood pressure and to identify factors associated with blood pressure control in a large German primary care sample. We used data from the German Metabolic and Cardiovascular Risk Study including 35 869 patients aged 18-99 years. High blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg or using antihypertensive therapy. Factors associated with blood pressure control among patients receiving antihypertensive therapy were examined using multiple logistic regressions to estimate odds ratios and 95% confidence intervals. The prevalence of high blood pressure, uncontrolled high blood pressure and untreated high blood pressure was 54.8%, 21.3% and 17.6%, respectively. Age >50 years (1.52; 1.40-1.65), male sex (1.30; 1.20-1.41), elevated waist circumference (1.55; 1.45-1.65), high cholesterol (1.24; 1.16-1.33), high triglycerides (1.11; 1.04-1.19) and concomitant diabetes (1.29; 1.20-1.40) were independently associated with uncontrolled high blood pressure. In a majority of patients we observed hypertension despite treatment for high blood pressures. Studies examining the reasons for treatment failure are highly warranted.

Candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in unselected patients with high or very high cardiovascular risk: efficacy, safety, and metabolic impact.

BACKGROUND AND OBJECTIVES: Safety and efficacy of the fixed-dose combination candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg has been demonstrated in a number of randomized clinical trials. Because stringent inclusion and exclusion criteria prohibit many high-risk patients from being investigated in clinical trials we aimed to assess the effectiveness, tolerability, and safety in a large unselected cohort of high-risk patients in primary care. The primary objective was the efficacy of candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in lowering the office-based blood pressure (BP). Secondary objectives were changes of metabolic parameters and safety. METHODS: A multicenter, non-interventional study of patients with a BP ≥ 140 mmHg systolic and/or 90 mmHg diastolic and additional cardiovascular risk factors. Patients received the fixed-dose combination of candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg for 24 weeks. RESULTS: A total of 3,390 patients with a mean age of 61.7 ± 10.6 years, 57.8 % being male, and a mean body mass index of 29.7 kg/m(2) were documented. Of these, 70.9 % had at least one additional cardiovascular risk factor such as coronary artery disease (45.5 %) or diabetes mellitus (44.5 %). Baseline BP was 159.6 ± 15.3 over 93.5 ± 9.5 mmHg. BP at 24 weeks was reduced by 32.3 ± 15.8 systolic and 16.1 ± 10.2 mmHg diastolic compared with baseline (p < 0.001 each). Systolic BP (SBP) and diastolic BP (DBP) was normalized (<140/<90 mmHg) in 57.4 % of non-diabetic patients. An SBP <140 mmHg or SBP reduction of ≥ 20 mmHg was achieved by 77.9 % non-diabetic patients. Fasting plasma glucose (-5.9 mg/dL), glycosylated hemoglobin (-0.18 %), low-density lipoprotein cholesterol (-8.5 mg/dL) and triglycerides (-20.3 mg/dL) were reduced significantly, high-density lipoprotein was increased by 0.18 %, while potassium and creatinine levels remained stable. The proportion of patients with adverse drug reactions (ADRs) was 1.3 % (n = 61 events in 45 patients). There were ten serious ADRs in eight patients; four patients died without causal relationship to study drug. CONCLUSIONS: The results confirm previous randomized clinical trial data supporting the effectiveness, tolerability, and safety of this fixed-dose combination in an unselected patient population with high cardiovascular risk.

Daytime systolic ambulatory blood pressure with a two-step switch from candesartan to olmesartan monotherapy and the fixed-dose combination of olmesartan/amlodipine in patients with uncontrolled essential hypertension (SEVICONTROL-2).

The objective of this study was to investigate the efficacy of the fixed-dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single-arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug-related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.

Daytime systolic ambulatory blood pressure with a direct switch between candesartan monotherapy and the fixed-dose combination olmesartan/amlodipine in patients with uncontrolled essential hypertension (SEVICONTROL-1).

A direct switch of candesartan to the fixed-dose combination olmesartan/amlodipine in uncontrolled hypertension is a frequent clinical requirement but is not covered by current labeling. An open-label, prospective, single-arm phase IIIb study was performed in patients with 32 mg candesartan followed by olmesartan/amlodipine 40/10 mg. The primary endpoint was change in mean daytime systolic blood pressure (BP). Mean daytime systolic BP was reduced by 9.2±12.6 mm Hg (P<.0001) after substituting candesartan for olmesartan/amlodipine (baseline BP 140.2±9.7 mm Hg). The reduction in office BP was 9.4±18.4/4.0±9.6 mm Hg; P<.002). Overall, 61.3% of patients achieved a target BP <140/90 mm Hg using office BP and <135/85 mm Hg using ambulatory BP measurement. There were 8 adverse events with a possible relation to study drug and 1 unrelated serious adverse events. In conclusion, patients with uncontrolled moderate arterial hypertension being treated using candesartan monotherapy achieve a further reduction of BP when switched directly to a fixed-dose combination of olmesartan 40 mg/amlodipine 10 mg.

Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice.

BACKGROUND: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ) as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. METHODS: In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. RESULTS: The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19), and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001), but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients, blood pressure was normalized (<140/90 mmHg). No noteworthy differences in baseline characteristics or baseline blood pressure were found between patients with an activity level (sum of weekly energy costs) above or below the median of 9,460.6. A higher versus lower physical activity score had no impact on blood pressure reduction. CONCLUSION: Our data confirm randomized trial data concerning safe and efficient blood pressure reduction using a fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent of physical activity level.

Validation of the Beurer BM 44 upper arm blood pressure monitor for home measurement, according to the European Society of Hypertension International Protocol 2002.

OBJECTIVE: The present study aimed to validate the automated upper arm blood pressure (BP) measuring device BM 44 for home BP monitoring according to the 2002 Protocol of the European Society of Hypertension. The most important new feature of the new device was an integrated 'WHO indicator', which categorizes the patient's individual result within the WHO recommendations for target BP by a coloured scale. METHODS: Systolic and diastolic BPs were measured sequentially in 35 adult participants (16 men, 19 women) using a standard mercury y-tubed reference sphygmomanometer (two observers) and the BM 44 device (one supervisor). Ninety-nine pairs of comparisons were obtained from 15 participants in phase 1 and a further 18 participants in phase 2 of the validation study. RESULTS: The BM 44 device passed phase 1 of the validation study successfully with a number of absolute differences between device and observers of 5, 10 and 15 mmHg for at least 28 out of 25, 35 out of 35 and 40 out of 40 measurements, respectively. The device also achieved the targets for phases 2.1 and 2.2, with 23 and 26 participants having had at least two of three device-observers differences within 5 mmHg for systolic and diastolic BP, respectively. CONCLUSION: The Beurer BM 44 upper arm BP monitor has passed the International Protocol requirements, and hence can be recommended for home use in adults.

Improved survival of patients with coronary artery disease and low ejection fraction with ICD implantation versus conventional therapy in a real world survey.

BACKGROUND: Coronary artery disease (CAD) is associated with an increased risk for sudden cardiac death. Randomized controlled trials have shown that implantable cardioverter defibrillators (ICD) improve life expectancy unless they are implanted within the first days after an acute myocardial infarction and guidelines recommend their use. We aimed to validate that these results also apply to patients of a typical community hospital in Germany. METHODS: This was a retrospective analysis of patients undergoing coronary angiography in the Lippe-Detmold Hospital between 2003 and 2006. They had to have significant CAD and an ejection fraction (EF) ≤ 35% and no acute myocardial infarction within 28 days of implantation and no history of ventricular fibrillation. RESULTS: 213 patients were included; 70 of which received an ICD. Patients with an ICD implantation were younger (64.8 ± 9.9 vs. 67.9 ± 9.8 years; p = 0.034), had single vessel CAD more frequently (22.9 vs. 11.2%; p = 0.025) and a lower EF (26.7 ± 6.3 vs. 29.1 ± 4.6%; p = 0.006). Hospital readmissions were comparable between the ICD and the control group (68.6 vs. 72.0%; p = 0.602). ICD therapy was associated with a considerable survival benefit compared to conventional therapy (HR 0.52; 95%CI 0.29-0.93; p = 0.027) in a Cox-Proportional Hazards Regression analysis. CONCLUSIONS: Appreciating the potential limitations of retrospective studies, we found that ICD use was associated with improved survival in patients with significant CAD and an EF <= 35% typical for a large tertiary hospital.

Health related quality of life in patients with critical limb ischemia.

Critical limb ischemia (CLI) is the terminal stage of peripheral artery disease. Research in recent years has been largely focussed on treatment options such as bypass surgery / endovascular treatment, surgery / primary amputation and additional benefits of supportive pharmacotherapy. Despite this plethora of treatment options, however, patients continue to have a reduced health related quality of life (HRQoL). Aim of the present work was to review the available evidence of improvement of HRQoL with regard to different treatment options. We found that a number of clinical studies have been conducted using HRQoL measures mostly as secondary outcomes in patients with CLI and other less severe forms of peripheral arterial disease. The studies demonstrate a consistent improvement of HRQoL over baseline within the first few months after the intervention. Prostaglandins, but no other pharmacotherapies, appear to be effective in patients without an option for revascularization. Due to a largely differing patient population under investigation and the different degrees of disease progression it appears difficult however to compare different treatment options with respect to their impact on HRQoL. HRQoL improvement as a predefined endpoint of novel therapeutic approach studies should be considered more consequently.