Reinhard G. Ketelhut

Regular exercise as an effective approach in antihypertensive therapy.

PURPOSE Exercise has been well documented to exert a beneficial effect on cardiovascular health. The effective control of arterial pressure (BP) is essential from the standpoint of cardiovascular prevention. So far, no study has determined the long-term effect of regular training as a monotherapy on both BP at rest and during exercise. METHODS Therefore, 10 subjects with hypertension (aged 43 +/- 3 yr) were studied in order to define BP response to long-term aerobic training. BP measurements were obtained at rest and during ergometry (50-100 W). Patients were instructed to exercise weekly (2 x 60 min aerobic exercise). RESULTS BP during exercise (100 W) did fall already after 6 months of regular training from 184 +/- 10/107 +/- 6 to 170 +/- 10/100 +/- 7, and this was associated with a 14% decrease in the rate-pressure product (at 100 W). After 18 months of training, there were further reductions in BP, at rest from 139 +/- 9/96 +/- 6 to 133 +/- 14/91 +/- 7 (P < 0.05) and during ergometry (100 W) from 184 +/- 10/107 +/- 6 to 172 +/- 8/96 +/- 6 mm Hg (P < 0.001). During a 3-yr follow-up, BP continued to decrease significantly to 130 +/- 13/87 +/- 7 mm Hg at rest and 167 +/- 9/92 +/- 6 mm Hg during exercise. No significant changes in body weight were documented during the training period. CONCLUSION The data demonstrate that long-term aerobic exercise is associated with a decrease in BP at rest and during exercise, which is comparable to that of drug therapies. This antihypertensive effect of regular training can be maintained as long as 3 yr.

Effectiveness and tolerability of a fixed-dose combination of olmesartan and amlodipine in clinical practice

Objectives: To assess the efficacy and tolerability of a fixed-dose combination of olmesartan and amlodipine in an unselected population of patients in primary care and to compare the results with recent randomized controlled trial evidence. Methods: A multicenter, noninterventional, noncontrolled observational study with 8241 hypertensive patients seen by 2187 physicians in daily practice. Blood pressure (BP) reduction, comorbid disease, pharmacotherapy, and tolerability were documented over a 12–18-week observational period. Results: Patients had a mean age of 62.8 ± 11.8 years (48.1% female), and 74.8% had at least one comorbid risk factor or condition. In total, 51.3% received olmesartan-amlodipine 20/5 mg, 30.6% received 40/5 mg, and 17.9% received 40/10 mg at baseline, mostly because of lack of efficacy on prior antihypertensive therapy (73.8%). BP at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg (39.8% had Grade 2 hypertension), and the observed BP reduction was −29.0 ± 17.1/−13.5 ± 10.9 mmHg (P < 0.0001), with a significant correlation between BP at baseline and BP reduction (Spearman’s Rho −0.811 for systolic BP and −0.759 for diastolic BP). BP reduction appeared to be dependent on dose and prior antihypertensive therapy, but not on age, gender, body mass index, duration of hypertension, or the presence of diabetes. At the final visit, 69.4% (4.3% at baseline) were controlled (<140/90 mmHg). Adverse drug reactions were observed in 2.76% of the study population; 94.25% of these adverse drug reactions were judged as nonserious events, and 31.5% of all adverse drug reactions reported were peripheral edema. Conclusion: The fixed-dose olmesartan-amlodipine combination was effective and well tolerated in an unselected population of patients in primary care practice. These results confirm prior randomized controlled trial evidence.

Improving quality of life in hypertension management using a fixed-dose combination of olmesartan and amlodipine in primary care.

Objectives. To assess quality of life (QoL) in unselected patients in primary care treated with a fixed-dose combination of olmesartan and amlodipine. Research design and methods. Multicenter, noninterventional, noncontrolled observational study in 8241 patients seen by 2187 physicians over 12 – 18 weeks. Main outcome measures. Changes in QoL were assessed by using the Short Form 12 (SF-12) questionnaire completed by 5434 patients (65.9%) at baseline and 4924 patients (59.8%) at the follow-up visit. Results. Patients had a mean age of 62.8 ± 11.8 years (48.1% female), mean blood pressure [BP] at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg and 74.8% had at least one co-morbid risk factor or condition. All 12 items of the SF-12 improved over the observational period (p < 0.0001) as did the physical (46.8 vs 40.4; p < 0.0001) and mental summary scores (52.4 vs 47.5; p < 0.0001). Correlations of changes in systolic and diastolic BP, pulse pressure and heart rate with scores were significant, although weak (maximum -0.2055 for physical health and changes in systolic blood pressure). Conclusions. The fixed-dose combination of olmesartan and amlodipine significantly improves QoL in an unselected population of patients in primary-care practice. This might translate into improved patient compliance and improved long-term antihypertensive efficacy.

Candesartan Cilexetil/Hydrochlorothiazide Treatment in High-Risk Patients with Type 2 Diabetes Mellitus and Microalbuminuria

AbstractBackground: Arterial hypertension complicated by the presence of diabetes mellitus and microalbuminuria is a particularly hazardous risk-factor combination. Blockers of the renin-angiotensin system have been shown to be beneficial with respect to these risk factors in randomized clinical trials. Objective: To provide proof of effectiveness for a fixed-dose combination such as candesartan cilexetil 16mg/hydrochlorothiazide (HCTZ) 12.5 mg in clinical practice within the context of a variety of concomitant diseases and medications. Methods: CHILI T2D was a non-interventional, open-label, non-controlled, multicentre study in clinical practice that evaluated 4110 patients with type 2 diabetes, uncontrolled hypertension and microalbuminuria who were being prescribed a fixed-dose combination of candesartan cilexetil 16mg/HCTZ 12.5 mg (Biopress®). Documented outcomes included blood pressure (BP) reductions, metabolic changes, changes in albuminuria, and adverse events throughout the 12-week treatment period. Results: Patients had a mean ±SD age of 64.0 ±10.3 years, 54.0% were male and the mean ±SD body mass index was 29.6 ±5.8 kg/m2. Coronary heart disease (34.3%), diabetic neuropathy (23.8%), retinopathy (18.6%) and heart failure (20.2%) were frequent co-morbidities. The use of candesartan cilexetil 16mg/HCTZ 12.5mg in patients with a mean ±SD baseline BP of 158.5±14.2/92.5 ±9.1 mmHg resulted in a substantial further reduction of office BP by a mean ±SD of −27.1 ±14.4/-13.1±9.5mmHg (p<0.001). The reduction was particularly pronounced in patients with severe hypertension (mean reduction of −44.7/−19.9 mmHg). Glucose (glycosylated haemoglobin [HbA1c], fasting blood glucose) as well as lipid parameters (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) were significantly improved (p< 0.001). Microalbuminuria, indicative of renal and cardiovascular risk, was significantly reduced by 28.8% (p< 0.001). Tolerability was excellent with only 16 out of 4110 patients experiencing any adverse event, of which six were considered to be serious. Conclusions: The fixed-dose combination of candesartan cilexetil 16 mg/HCTZ 12.5 mg is highly effective in lowering blood pressure in type 2 diabetic patients with all stages of hypertension and microalbuminuria. The data indicate that low-dose HCTZ can safely be added to an existing drug regimen in this patient group to increase the BP-lowering effect, without compromising tolerability and the favourable metabolic profile of candesartan cilexetil monotherapy.

Candesartan Cilexetil/Hydrochlorothiazide Treatment in High-Risk Patients with Type 2 Diabetes Mellitus and Microalbuminuria The CHILI T2D Study

BACKGROUND Arterial hypertension complicated by the presence of diabetes mellitus and microalbuminuria is a particularly hazardous risk-factor combination. Blockers of the renin-angiotensin system have been shown to be beneficial with respect to these risk factors in randomized clinical trials. OBJECTIVES To provide proof of effectiveness for a fixed-dose combination such as candesartan cilexetil 16 mg/hydrochlorothiazide (HCTZ) 12.5 mg in clinical practice within the context of a variety of concomitant diseases and medications. METHODS CHILI T2D was a non-interventional, open-label, non-controlled, multicentre study in clinical practice that evaluated 4110 patients with type 2 diabetes, uncontrolled hypertension and microalbuminuria who were being prescribed a fixed-dose combination of candesartan cilexetil 16 mg/HCTZ 12.5 mg (Blopress). Documented outcomes included blood pressure (BP) reductions, metabolic changes, changes in albuminuria, and adverse events throughout the 12-week treatment period. RESULTS Patients had a mean +/- SD age of 64.0 +/- 10.3 years, 54.0% were male and the mean +/- SD body mass index was 29.6 +/- 5.8 kg/m2. Coronary heart disease (34.3%), diabetic neuropathy (23.8%), retinopathy (18.6%) and heart failure (20.2%) were frequent co-morbidities. The use of candesartan cilexetil 16 mg/HCTZ 12.5 mg in patients with a mean +/- SD baseline BP of 158.5 +/- 14.2/92.5 +/- 9.1 mmHg resulted in a substantial further reduction of office BP by a mean +/- SD of -27.1 +/- 14.4/-13.1 +/- 9.5 mmHg (p < 0.001). The reduction was particularly pronounced in patients with severe hypertension (mean reduction of -44.7/-19.9 mmHg). Glucose (glycosylated haemoglobin [HbA(1c)], fasting blood glucose) as well as lipid parameters (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) were significantly improved (p < 0.001). Microalbuminuria, indicative of renal and cardiovascular risk, was significantly reduced by 28.8% (p < 0.001). Tolerability was excellent with only 16 out of 4110 patients experiencing any adverse event, of which six were considered to be serious. CONCLUSIONS The fixed-dose combination of candesartan cilexetil 16 mg/HCTZ 12.5 mg is highly effective in lowering blood pressure in type 2 diabetic patients with all stages of hypertension and microalbuminuria. The data indicate that low-dose HCTZ can safely be added to an existing drug regimen in this patient group to increase the BP-lowering effect, without compromising tolerability and the favourable metabolic profile of candesartan cilexetil monotherapy.

Favorable effect of aerobic exercise on arterial pressure and aortic pulse wave velocity during stress testing

BACKGROUND Increased central pulse wave velocity is a major risk factor for cardiovascular disease. The favorable influence of exercise on arterial stiffness (AS) and blood pressure (BP) has been reported exclusively at rest. The present study investigated the influence of a single bout of acute cycling on AS and BP during recovery and, moreover, during cold pressor stress testing. PROBANDS AND METHODS 32 healthy men (33.7 ± 8 years, BMI 24 ± 2.5 kg/m²) performed a 60 minute endurance exercise on a bicycle ergometer (45 % VO2max). Before and after exercise aortic pulse wave velocity (aPWV) as well as central and peripheral BP were measured non-invasively at rest and at the end of a 2 minute cold pressor test (CPT). RESULTS Even after 60 minutes of recovery aPWV (- 0.22 ± 0.3 m / sec) was significantly reduced (p < 0.01). Exercise decreased peripheral (- 8 ± 7 mmHg) and central (- 7 ± 8 mmHg) systolic BP as well as peripheral (- 3 ± 5 mmHg) and central (- 4 ± 7 mmHg) diastolic BP (p < 0.01). In comparison to measurements during CPT pre-exercise, there was a significant reduction in aPWV (- 0.19 ± 0.3 m / sec), peripheral (- 6 ± 10 mmHg) and central (- 5 ± 8 mmHg) systolic BP as well as peripheral (- 3 ± 6 mmHg) and central (- 3 ± 6 mmHg) diastolic BP during CPT after exercise (p < 0.01). CONCLUSIONS The present study suggests that acute endurance exercise leads not only to decreased BP but even more reduces aPWV as a measure of AS even after 60 minutes of recovery. In particular, the investigation provides evidence that acute moderate-intensity exercise has a favorable effect on BP and aPWV during stress testing.

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.

Influence of a high-intensity interval training session on peripheral and central blood pressure at rest and during stress testing in healthy individuals

BACKGROUND Regular physical activity is known to reduce arterial pressure (BP). In a previous investigation, we could prove that even a single bout of moderate-intensity continuous exercise (MICE) causes a prolonged reduction in BP. Whether high-intensity interval training (HIIT) has a favourable influence on BP, and therefore may be followed subjects and methods by a prolonged BP reduction, should be examined on the basis of blood pressure response after exercise and during a subsequent stress test. PATIENTS AND METHODS In 39 healthy men (aged 34 ± 8 years, BMI 24 ± 2), peripheral and central BP were measured noninvasively at rest and at the end of a 2-min cold pressor test (CPT) using a Mobil-O-Graph (24 PWA monitor, IEM). Following HIIT (6 x 1 min at 98% of the previously determined maximum wattage, 4-min rest between intervals) BP was measured again throughout 60 min of rest and thereafter during a CPT. The results were compared with those obtained before HIIT. RESULTS Similar to MICE, peripheral and central BPs were significantly (p < 0.05) lower 45 min after HIIT. When analysing peripheral BP during a CPT before and after exercise, significantly lower systolic (p < 0.001) and diastolic (p = 0.008) pressures were established after HIIT. This was true for systolic (p = 0.002) and diastolic (p = 0.006) central BP as well. Although there were no more significant differences between pressures at rest before and 60 min after exercise, the increase in peripheral systolic pressure due to CPT was significantly slower after HIIT (p = 0.019) when compared with BP during CPT before exercise. This was true for central systolic BP as well (p = 0.017). CONCLUSION HIIT leads to a BP reduction, which can still be detected up to 45 min after completion of the training. Even 60 min after exercise, pressures during a CPT showed a reduced augmentation, indicating an attenuated hemodynamic response to stress testing after HIIT.

Hypertonie bei Marathonläufern

R Ausdauertraining kann nicht nur den Blutdruck von Hypertonikern senken [1], sondern auch der Entwicklung einer arteriellen Hypertonie bzw. altersbedingten Blutdruckanstieges entgegenwirken [2]. So ist bei gut trainierten Ausdauersportlern eher ein normaler bzw. niedriger Blutdruck zu erwarten als bei untrainierten Personen. Nachfolgend berichten wir über einen Marathonläufer, der in unserer Hochdrucksprechstunde vorstellig wurde.

Daily Physical Activity Improves Vascular Function and Motor Skills in Children

The literature is consistent that regular physical activity in children has to be increased in order to compensate the negative health effects resulting from growing sedentary lifestyle. Thus, we analyzed in 45 students (aged 6.6 ± 0.7 years) the effects of a regular exercise intervention, on top of the normal physical education classes, on motor performance (MP) and hemodynamic parameters. The students were randomized either to an intervention (INT) (n = 23) or a control (CON) (n = 22) group. Throughout a 9 months period, INT received additional exercise interventions two days a week for 45 minutes. The main outcome measures were MP, peripheral and central blood pressure (BP), augmentation index (Alx) and aortic pulse wave velocity (aPWV). After the exercise intervention, we found significant (P < 0.05) positive effects on various test items of MP and significant decreases in peripheral and central systolic BP in INT. In contrast, in CON the respective parameters increased in CON after the observation period. Moreover, aPWV decreased significantly in INT (P = 0.047) and increased in CON, thus resulting in a significant difference in the mean change (P = 0.043). There were no considerable changes in AIx in both groups. In conclusion, we demonstrated that an increase in regular physical activity has a positive influence on development of MP and hemodynamic parameters even in early childhood. The findings of this study suggest that an increase in exercise time should be initiated as early as possible to improve motor ability and prevent future cardiovascular risk.