Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 2.

BACKGROUND: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. METHODS: Generation of evidence and search of literature have been described in part 1. RESULTS: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. CONCLUSIONS: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.

[Hypertensive emergencies]. / Der hypertensive Notfall.

Hypertensive urgency and hypertensive emergency are associated with sudden, massive rise in blood pressure. An acute increase in blood pressure to values above 180/120 mmHg is considered critical. If not treated in time, it can quickly enter a life-threatening hypertensive emergency. The symptoms or organ damage determine the assessment as a crisis or an emergency. Rapid action is required. The therapy depends on the severity and the organ involvement. However the general principal is to avoid therapeutically induced hypotension.

Exercise-based cardiac rehabilitation in twelve European countries results of the European cardiac rehabilitation registry.

AIM: Results from EuroCaReD study should serve as a benchmark to improve guideline adherence and treatment quality of cardiac rehabilitation (CR) in Europe. METHODS AND RESULTS: Data from 2.054 CR patients in 12 European countries were derived from 69 centres. 76% were male. Indication for CR differed between countries being predominantly ACS in Switzerland (79%), Portugal (62%) and Germany (61%), elective PCI in Greece (37%), Austria (36%) and Spain (32%), and CABG in Croatia and Russia (36%). A minority of patients presented with chronic heart failure (4%). At CR start, most patients already were under medication according to current guidelines for the treatment of CV risk factors. A wide range of CR programme designs was found (duration 3 to 24weeks; total number of sessions 30 to 196). Patient programme adherence after admission was high (85%). With reservations that eCRF follow-up data exchange remained incomplete, patient CV risk profiles experienced only small improvements. CR success as defined by an increase of exercise capacity >25W was significantly higher in young patients and those who were employed. Results differed by countries. After CR only 9% of patients were admitted to a structured post-CR programme. CONCLUSIONS: Clinical characteristics of CR patients, indications and programmes in Europe are different. Guideline adherence is poor. Thus, patient selection and CR programme designs should become more evidence-based. Routine eCRF documentation of CR results throughout European countries was not sufficient in its first application because of incomplete data exchange. Therefore better adherence of CR centres to minimal routine clinical standards is requested.

Efficacy and tolerability of combination therapy with valsartan plus hydrochlorothiazide compared with amlodipine monotherapy in hypertensive patients with other cardiovascular risk factors: the VAST study.

BACKGROUND: Recent antihypertensive treatment guidelines recommend greater use of combination therapies. OBJECTIVES: The primary objective of this study was to determine whether combination therapy with valsartan 160 mg plus hydrochlorothiazide (HCTZ) 25 mg OD would be more effective than monotherapy with amlodipine 10 mg OD in reducing systolic blood pressure (SBP) in patients with moderate (stage II) hypertension and > or =1 other cardiovascular risk factor or concomitant condition. A secondary objective was to assess the effects of the study treatments on circulating markers of endothelial dysfunction and vascular inflammation. METHODS: This was a multicenter, randomized, double-blind, active-controlled, 24-week study. After a 2-week, single-blind, placebo run-in period, patients were randomized to 3 groups, 2 of them receiving valsartan 160 mg OD and 1 receiving amlodipine 5 mg OD. At week 4, HCTZ 12.5 mg OD was added to valsartan in one of the treatment groups (V+HCTZ12.5), HCTZ 25 mg OD was added to the other (V+HCTZ25), and the amlodipine dose was force-titrated to 10 mg OD (A10). The primary efficacy variable was change in mean sitting SBP at week 24. Other variables were changes in mean sitting diastolic blood pressure (DBP) and mean pulse pressure (PP) from baseline, and response rate (systolic response defined as mean sitting SBP <140 mm Hg or a reduction in mean sitting SBP of > or =20 mm Hg from baseline; diastolic response defined as mean sitting DBP <90 mm Hg or a reduction in mean sitting DBP of > or =10 mm Hg from baseline). Changes in the following markers of endothelial dysfunction were determined at baseline and weeks 4, 12, and 24 in all randomized patients from the participating European and South African centers: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), vascular tissue plasminogen activator (t-PA) antigen, and oxidized low-density lipoprotein (LDL). RESULTS: The study enrolled 1088 patients with moderate hypertension (mean age, 61 years; 82% white; 53% women). The intent-to-treat population consisted of 1079 patients: 357 in the V+HCTZ12.5 group, 363 in the V+HCTZ25 group, and 359 in the A10 group. At baseline, the groups were comparable in terms of blood pressure and most other characteristics; the only statistically significant difference between groups was in the proportion of patients aged > or =65 years, which was lower in the amlodipine group (P = 0.01). At the end of the study, the least squares mean (SD) changes from baseline in mean sitting SBP were 27.1 (13.7), 29.7 (13.7), and 27.6 (13.8) mm Hg in the V+HCTZ12.5, V+HCTZ25, and A10 groups, respectively, with corresponding percent changes of 16%, 18%, and 17% (P < 0.05, V+HCTZ25 vs A10). The changes in mean sitting DBP did not differ significantly between groups. The reductions in PP were 17.5 (11.3), 18.7 (11.3), and 16.9 (11.3) mm Hg, with percent changes of 24%, 26%, and 23% (P < 0.05, V+HCTZ25 vs A10). Significant reductions in t-PA antigen were observed in both combination-therapy groups compared with the amlodipine monotherapy group at week 12 (P < 0.05); the reductions remained significant through the end of the study in the V+HCTZ12.5 group. There was a significant reduction in IL-6 and hs-CRP at week 12 with V+HCTZ25 compared with A10 (P < 0.05). Oxidized LDL values were reduced by approximately 10% with all treatments. Rates of total adverse events were significantly lower with the valsartan-based treatments compared with amlodipine monotherapy (49.7%, 49.6%, and 67.5% with V+HCTZ12.5, V+HCTZ25, and A10, respectively; P < 0.05). Rates of total discontinuations were a respective 10.1%, 9.0%, and 24.5%, and discontinuation rates due to AEs were 4.2%, 3.5%, and 18.2%. Leg edema was more common with amlodipine monotherapy than with the valsartan-based combinations (P < 0.05). CONCLUSION: In this group of patients with moderate hypertension and > or =1 other cardiovascular risk factor or concomitant condition, similar and greater antihypertensive effects were seen with the fixed-dose combinations of valsartan 160 mg and HCTZ 12.5 and 25 mg OD, respectively, compared with amlodipine 10 mg OD, with significantly lower rates of treatment-related adverse events and possible beneficial effects on vascular markers.

Long-acting blood pressure reduction by candesartan cilexetil in patients with hypertension.

Candesartan cilexetil is a highly potent and long-acting angiotensin II type I (AT1) receptor antagonist. This short review summarises results of clinical studies focusing on the duration of action of candesartan cilexetil. Results of previous clinical studies indicate that candesartan has the property to maintain a sustained blood pressure reduction for up to 48 h after dosing. Since lack of compliance is a known problem in patients with hypertension, these findings could be of particular clinical relevance.

Risk factors for, and prevalence of, sleep apnoea in cardiac rehabilitation facilities in Germany: The Reha-Sleep registry.

AIM: To determine the prevalence of, and the risk factors for, sleep apnoea in cardiac rehabilitation (CR) facilities in Germany. METHODS: 1152 patients presenting for CR were screened for sleep-disordered breathing with 2-channel polygraphy (ApneaLink™; ResMed). Parameters recorded included the apnoea-hypopnoea index (AHI), number of desaturations per hour of recording (ODI), mean and minimum nocturnal oxygen saturation and number of snoring episodes. Patients rated subjective sleep quality on a scale from 1 (poor) to 10 (best) and completed the Epworth Sleepiness Scale (ESS). RESULTS: Clinically significant sleep apnoea (AHI ≥15/h) was documented in 33% of patients. Mean AHI was 14 ± 16/h (range 0-106/h). Sleep apnoea was defined as being of moderate severity in 18% of patients (AHI ≥15-29/h) and severe in 15% (AHI ≥30/h). There were small, but statistically significant, differences in ESS score and subjective sleep quality between patients with and without sleep apnoea. Logistic regression model analysis identified the following as risk factors for sleep apnoea in CR patients: age (per 10 years) (odds ratio (OR) 1.51; p<0.001), body mass index (per 5 units) (OR 1.31; p=0.001), male gender (OR 2.19; p<0.001), type 2 diabetes mellitus (OR 1.45; p=0.040), haemoglobin level (OR 0.91; p=0.012) and witnessed apnoeas (OR 1.99; p<0.001). CONCLUSIONS: The findings of this study indicate that more than one-third of patients undergoing cardiac rehabilitation in Germany have sleep apnoea, with one-third having moderate-to-severe SDB that requires further evaluation or intervention. Inclusion of sleep apnoea screening as part of cardiac rehabilitation appears to be appropriate.

Fixed combination of candesartan with hydrochlorothiazide in patients with severe primary hypertension.

OBJECTIVE: The new guidelines for treatment of hypertension by the JNC VII in 2003 permit the initial use of a combination therapy, if blood pressure has to be lowered more than 20/10 mmHg. The aim of this investigation was to document the efficacy and safety of a combination therapy with candesartan cilexetil and hydrochlorothiazide in severe hypertension. METHODS: 116 patients freshly diagnosed as having severe primary hypertension (Grade III) and untreated for this condition were enrolled. The study was performed without a placebo control group for ethical reasons. Thus, all patients were treated for 6 weeks with 16 mg candesartan cilexetil plus 12.5mg hydrochlorothiazide daily after forced titration with 8 and 16 mg candesartan cilexetil each for

Candesartan cilexetil/hydrochlorothiazide combination treatment versus high-dose candesartan cilexetil monotherapy in patients with mild to moderate cardiovascular risk (CHILI Triple T).

BACKGROUND: Candesartan cilexetil has been shown to effectively reduce blood pressure and cardiovascular risk. Whether it is advantageous to combine candesartan cilexetil with low-dose hydrochlorothiazide (HCTZ) or uptitrate it in cases of insufficient blood pressure control has not been fully investigated under routine clinical conditions. METHODS: CHILI Triple T is a prospective, noninterventional, observational study. Patients with uncontrolled hypertension and added cardiovascular risk received a fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg (combination therapy group) or high-dose monotherapy with candesartan cilexetil 32 mg (high-dose monotherapy group). RESULTS: A total of 4600 patients with a mean age of 63.1 ± 11.0 years, of which 44.7% were female, was included. The combination therapy group had 3337 patients, and the high-dose monotherapy group 1263 patients. Patients in both treatment groups were comparable with respect to age and gender, but patients receiving high-dose monotherapy had a slightly higher mean systolic blood pressure, more prior revascularizations, renal insufficiency, diabetic nephropathy, peripheral artery disease, and a lower ankle brachial index. The use of combination therapy resulted in a blood pressure reduction of -28.5 ± 13.8/-14.2 ± 9.4 mm Hg (P < 0.001 vs 160.2 ± 13.3/94.5 ± 8.2 mm Hg at baseline). The use of high-dose monotherapy reduced blood pressure by -29.73 ± 15.3/-14.1 ± 9.6 mm Hg (P < 0.001 vs 162.4 ± 14.7/94.7 ± 8.7 mm Hg at baseline). Differences in subgroups of patients defined by age, gender, body mass index, dyslipidemia, waist circumference, smoking, prior cardiovascular event, glomerular filtration rate, and microalbuminuria were minor, although partially significant. Tolerability was excellent, with only 28 out of 3358 patients (0.8%) in the combination therapy group and 15 out of 1273 patients (1.2%) in the high-dose monotherapy group experiencing any adverse event, of which one in each group was considered to be serious (<0.1%). CONCLUSIONS: Both the fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg and high-dose monotherapy with candesartan 32 mg were highly effective in lowering blood pressure in patients at increased cardiovascular risk. Tolerability was excellent. The choice of either strategy therefore largely depends on the principal aim: blood pressure reduction with pronounced volume restriction or pronounced additional end-organ protection.

Antihypertensive efficacy and tolerability of candesartan-hydrochlorothiazide 32/12.5 mg and 32/25 mg in patients not optimally controlled with candesartan monotherapy.

AIM: To evaluate the efficacy and tolerability of candesartan cilexetil 32 mg in combination with hydrochlorothiazide (HCT) 12.5 mg or 25 mg in hypertensive patients not optimally controlled with candesartan monotherapy. PATIENTS AND METHODS: A total of 3521 patients with treated or untreated hypertension and sitting diastolic blood pressure (DBP) 90-114 mmHg, entered a single-blind run-in phase with candesartan (16 mg for 2 weeks, followed by 32 mg for 6 weeks). At the end of the run-in phase, 1975 patients who still had DBP 90-114 mmHg were randomized to 8 weeks' double-blind treatment with either candesartan 32 mg (n=654), or candesartan-HCT 32/12.5 mg (n=656), or candesartan-HCT 32/ 25 mg (n=665). PRINCIPAL RESULTS: At randomization, the mean blood pressure was similar in the three treatment groups (approximately 153/97 mmHg). It was reduced during the double-blind treatment phase by 6.1/5.6 mmHg in the candesartan 32 mg group, by 13.0/8.8 mmHg in the candesartan-HCT 32/12.5 mg group, and by 15.5/10.0 mmHg in the candesartan-HCT 32/25 mg group (p<0.01 for all between treatment comparisons). All study treatments were generally well tolerated. CONCLUSION: Candesartan-HCT 32/12.5 mg and candesartan-HCT 32/25 mg are highly effective and provide improved blood pressure reduction and blood pressure control relative to candesartan 32 mg monotherapy, with maintained tolerability, in hypertensive patients whose blood pressure is not optimally controlled with candesartan monotherapy. Furthermore, candesartan-HCT 32/25 mg is more effective than candesartan-HCT 32/12.5 mg in this population.

[The role of adiposity and inactivity in primary prevention of cardiovascular disease]. / Bedeutung von Adipositas und Bewegungsmangel in der kardiovaskulären Primärprävention.

The important role of obesity and inactivity in the pathogenesis of cardiovascular diseases is generally accepted. In Germany, 75% of men and 59% of women at the age of 25-69 years are overweight or obese. The prevalence of inactivity in Germany is 30% for all age groups, and only 13% of the population achieves a level of physical activity known to have cardioprotective effects. Overweight and inactivity have shown to be associated with several cardiovascular risk factors such as hypertension, diabetes mellitus type 2 and dyslipoproteinemia. It has been demonstrated that obesity (body mass index > 30 kg/m2) considerably increases the risk for cardiovascular diseases (by up to 50%). Comparable findings have been observed in a meta-analysis when the effects of inactivity on cardiovascular morbidity or mortality have been investigated. Compared to regular physical activity, inactivity increased the relative risk for myocardial infarction or death by 60% and 90%, respectively. Therapeutic lifestyle changes (TLC) by increased physical activity and dietary intervention have shown to reduce cardiovascular risk factors and the incidence and prevalence of cardiovascular disease. Therefore, TLC should be the primary intervention in inactive overweight or obese subjects. This recommendation is specifically important for patients with the metabolic syndrome.