Peter Bramlage

High prevalence and poor control of hypertension in primary care: cross-sectional study.

Objective To report: (1) on the background, design and methods of the Hypertension and Diabetes Risk Screening and Awareness (HYDRA) study, (2) on the point prevalence of hypertension in primary care and (3) on the proportion of treated, controlled, and uncontrolled hypertension. Design Cross-sectional point prevalence study. Setting Representative nationwide sample of 1912 primary care practices in Germany. Participants A total of 45 125 unselected primary care attendees. Main outcome measures Prevalence of hypertension based on doctors diagnosis, self-reported diagnosis, and blood pressure (BP) measurements. Results A total of 39% of all patients and 67% of patients aged 60 years or older, respectively, were diagnosed by their doctors as having hypertension. Eighty-four percent of diagnosed patients were on antihypertensive medication, 57% of which were rated by the physician as well controlled. When hypertension was defined as either current BP levels ⩾ 140/90 mmHg and/or current antihypertensive medication, the total point prevalence increased to 50%, while treatment and control rates (BP < 140/90 mmHg) dropped to 64 and 19%, respectively. Conclusions Extrapolation of these findings to the entire primary care patient population seen in the over 20 000 primary care practices in Germany suggests that on an average day, over 700 000 patients with elevated BP are seen by primary care physicians, but that only around 132 000 of these patients are well controlled. Thus, this study not only documents the enormous burden of hypertensive patients in the primary health system, but also highlights the alarming lack of BP control in the vast majority of hypertensive patients.

Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal.

Atherosclerotic peripheral artery disease (PAD) is a common manifestation of atherosclerosis. The occlusion of large limb arteries leads to ischaemia with claudication which can progress to critical limb ischaemia (CLI) with pain at rest, and to tissue loss. At present, common therapy for CLI is either surgical or endovascular revascularisation aimed at improving blood flow to the affected extremity. However, major amputation and death are still frequent complications. Exploring new strategies for revascularisation of ischaemic limbs is thus of major importance. Bone marrow (BM)-derived stem and progenitor cells have been identified as a potential new therapeutic option to induce therapeutic angiogenesis. Encouraging results of preclinical studies have rapidly led to several small clinical trials, in which BM-derived mononuclear cells were administered to patients with limb ischaemia. Clinical benefits were reported from these trials including improvement of ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcPO2), reduction of pain, and decreased need for amputation. Nonetheless, large randomised, placebo-controlled, double-blind studies are necessary and currently ongoing (BONMOT-CLI, JUVENTUS and NCT00498069). Further research relates to the optimal cell type and dosage, the isolation method, the role of colony-stimulating factors, administration route, and the supportive stimulation of cells with reduced functioning due to advanced PAD. Autologous stem cell therapy for ischaemic peripheral disease seems to be a promising new tool for the treatment of severe limb ischaemia. Preliminary evidence has established its safety, feasibility and effectiveness on several important endpoints. Several large endpoints studies are underway to further consolidate this evidence.

Treatment of peripheral arterial disease using stem and progenitor cell therapy

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome associated with significant morbidity and mortality. PAD is most commonly caused by atherosclerosis obliterans (ASO) and thromboangiitis obliterans (TAO), and can lead to claudication and critical limb ischemia (CLI), often resulting in a need for major amputation and subsequent death. Standard treatment for such severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for such interventions, due to high operative risk or unfavorable vascular involvement. Therefore, new strategies are needed to offer these patients a viable therapeutic option. Bone-marrow derived stem and progenitor cells have been identified as a potential new therapeutic option to induce angiogenesis. These findings prompted clinical researchers to explore the feasibility of cell therapies in patients with peripheral and coronary artery disease in several small trials. Clinical benefits were reported from these trials including improvement of ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcO(2)), reduction of pain, and decreased need for amputation. Nonetheless, large randomized, placebo-controlled, double-blind studies are necessary and currently ongoing to provide stronger safety and efficacy data on cell therapy. Current literature is supportive of intramuscular bone marrow cell administration as a relatively safe, feasible, and possibly effective therapy for patients with PAD who are not subjects for conventional revascularization.

β1-Adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

Abstract.A substantial body of evidence suggests involvement of the human β1-adrenoceptor (β1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. β1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49–Gly, Ala-59–Ser, Gly-389–Arg, Arg-399–Cys, His-402–Arg, Thr-404–Ala, and Pro-418–Ala. These mutations resulted in 11 different β1-AR genotypes. Importantly, the genotypes carrying the Ser-49–Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.

Low-grade albuminuria and cardiovascular risk : what is the evidence?

Microalbuminuria (MA), conventionally defined as a urinary albumin excretion (UAE) of 30–300 mg/day, is recognised as a marker of endothelial dysfunction. Furthermore, it represents an established risk factor for cardiovascular morbidity and mortality and for end-stage renal disease in individuals with an adverse cardiovascular risk profile. It is common in the general population, particularly in patients with diabetes mellitus or arterial hypertension. There is growing evidence from prospective observational trials that UAE levels well below the current MA threshold (“lowgrade MA”) are also associated with an increased risk of incident cardiovascular disease and allcause mortality. Even in apparently healthy individuals (without diabetes or hypertension), such an association has been shown. As albuminuria screening assays that are reliable even in the lower ranges are commercially available, there may be an important clinical role for MA in disease screening, comparable to the role of blood pressure and lipid screening. MA is modifiable, and the inhibition of the renin-angiotensin system by ACE inhibitors and AT1 receptor antagonists has been shown to result in a lower incidence of cardiovascular events.

Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation: The Prospective, Randomized, Controlled, Noninferiority FreezeAF Study

Background— There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Methods and Results— In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, −0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, −0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002). Conclusion— This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774566.

Impact of 4 different definitions used for the assessment of the prevalence of the Metabolic Syndrome in primary healthcare:The German Metabolic and Cardiovascular Risk Project (GEMCAS)

BackgroundThe metabolic syndrome (MetSyn) places individuals at increased risk for type 2 diabetes and cardiovascular disease. Prevalence rates of the population of the MetSyn are still scarce. Moreover, the impact of different definitions of the MetSyn on the prevalence is unclear. Aim here is to assess the prevalence of the MetSyn in primary health care and to investigate the impact of four different definitions of the MetSyn on the determined prevalence with regard to age, gender and socio-economic status.MethodsThe German-wide cross-sectional study was conducted during two weeks in October 2005 in 1.511 randomly selected general practices. Blood samples were analyzed, blood pressure and waist circumference assessed, data on lifestyle, medication, chronic disorders, and socio-demographic characteristics collected. MetSyn prevalence was estimated according to the definitions of NCEP ATP III (2001), AHA/NHLBI (2004, 2005), and IDF (2005). Descriptive statistics and prevalence rate ratios using the PROG GENMOD procedure, were calculated. Cohens kappa was used as measure for interreliability between the different prevalence estimates.ResultsData of 35,869 patients (age range: 18–99, women 61.1%) were included. The prevalence was lowest using the NCEP ATP III- (all: 19.8%, men 22.7%, women: 18.0%), highest according to the IDF-definition (32.7%, 40.3%, 28.0%). The increase in prevalence with recent definitions was more pronounced for men than for women, and was particularly high for men and women aged 60–79 years. The IDF-definition resulted in a higher prevalence especially in those with the highest educational status. Agreement (kappa) between the NCEP ATP III- and IDF-definition was 0.68 (men 0.61, women 0.74), between the updated the AHA/NHLBI- (2005) and IDF-definition 0.85 (men 0.79, women 0.89).ConclusionThe prevalence of metabolic syndrome is associated with age, gender, and educational status and increases considerably with each newly published definition. Our data highlight the need for a better evidence regarding thresholds of the components of the metabolic syndrome, especially with regard to the IDF-definition – according to which in some populations a majority of subjects are diagnosed with the metabolic syndrome.

A Global Perspective on Blood Pressure Treatment and Control in a Referred Cohort of Hypertensive Patients

J Clin Hypertens (Greenwich). 2010;12:666–677. ©2010 Wiley Periodicals, Inc.

Association of cardiovascular risk factors with microalbuminuria in hypertensive individuals: the i-search global study

Objectives To define the prevalence of microalbuminuria (MAU) in hypertensive outpatients attending a cardiologist or internist (i-SEARCH A) and to compare hypertensive outpatients with or without coronary artery disease (CAD; i-SEARCH B). A secondary objective was to establish a correlation between MAU and known cardiovascular risk factors. Methods i-SEARCH was an international, observational study. which enrolled consecutive outpatients with hypertension. Patients with reasons for a false-positive MAU test were excluded. Main outcome measures were the prevalence of MAU as assessed using a dipstick test, hypertension co-morbidities, co-medication and presence of known cardiovascular risk factors. Results A total of 21 050 patients, from 26 countries, were included in the primary analysis. Overall prevalence of MAU was 58.4% (men > women), although there was considerable variation in prevalence across countries and continents (maximum 71% in Vietnam/Indonesia; minimum 53% in Germany/Switzerland). In multivariate analyses, predictors of MAU were identified to be male gender, high waist circumference, systolic blood pressure ≥ 120 mmHg, diastolic blood pressure ≥ 100 mmHg, creatinine clearance ≥ 50 ml/min, and the presence of diabetes, congestive heart failure, CAD, history of cerebral pathology, peripheral arterial disease, dyspnoea or palpitations. MAU was present more often in patients with CAD than in patients without. Conclusions MAU is extremely common in hypertensive outpatients worldwide, especially in patients with known cardiovascular risk factors. Given its importance as a strong, early and independent marker of increased cardiovascular risk in hypertension, the results of i-SEARCH mandate more rigorous MAU screening of hypertensive patients in clinical practice.

Abdominal obesity is associated with microalbuminuria and an elevated cardiovascular risk profile in patients with hypertension.

Background Overweight and obesity are frequently associated with preventable death and have emerged as a major challenge to public health. There is an ongoing debate on the role of abdominal obesity and its value in predicting cardiovascular and renal outcomes. The present analysis evaluates the prevalence of microalbuminuria (MAU) and conventional cardiovascular risk factors in relation to measures of general and abdominal obesity. Methods In this multinational, observational study, 20828 hypertensive out-patients from 26 countries including Europe, North and Latin America, Middle East, and Asia were analyzed. Urinary dipstick screening for MAU was performed as well as data on patient demographics, anthropometric measures, cardiovascular risk factors, comorbid conditions, and cardiovascular drug therapy collected. MAU prevalence was determined by a stepwise logistic regression analysis with cardiovascular risk factors as univariate. Results In the univariate analysis, MAU prevalence systematically increased with body mass index (BMI) from 54.4% (1st tertial) to 62.1% (3rd tertial) (p < 0.0001), an increase which was also observed for waist circumference (WC). At any level of BMI, MAU increased with WC from 53.5%, 54.8%, and 55.0% (1st tertial of WC in all three BMI tertials) to 61.4%, 62.1%, and 64.0% (3rd tertial of WC in all BMI tertials) (p < 0.0001). In the multivariate analysis, WC, but not BMI was independently associated with MAU. Furthermore, overweight/obesity were associated with the presence of modifiable and nonmodifiable risk factors. Conclusion An abnormal WC, but not BMI appears to be independently associated with MAU, an early marker of cardiovascular and renal risk. Increasing WC confers an incremental risk for MAU at any level of BMI, underlining the prognostic importance of abdominal fat accumulation beyond general obesity.