A High-Protein and Low-Glycemic Formula Diet Improves Blood Pressure and Other Hemodynamic Parameters in High-Risk Individuals.

Low-caloric formula diets can improve hemodynamic parameters of patients with type 2 diabetes. We, therefore, hypothesized that persons with overweight or obesity can benefit from a high-protein, low-glycemic but moderate-caloric formula diet. This post-hoc analysis of the Almased Concept against Overweight and Obesity and Related Health Risk- (ACOORH) trial investigated the impact of a lifestyle intervention combined with a formula diet (INT, n = 308) compared to a control group with lifestyle intervention alone (CON, n = 155) on hemodynamic parameters (systolic and diastolic blood pressure (SBP, DBP), resting heart rate (HR), and pulse wave velocity (PWV)) in high-risk individuals with prehypertension or hypertension. INT replaced meals during the first 6 months (1 week: 3 meals/day; 2−4 weeks: 2 meals/day; 5−26 weeks: 1 meal/day). Study duration was 12 months. From the starting cohort, 304 (68.3%, INT: n = 216; CON: n = 101) participants had a complete dataset. Compared to CON, INT significantly reduced more SBP (−7.3 mmHg 95% CI [−9.2; −5.3] vs. −3.3 mmHg [−5.9; −0.8], p < 0.049) and DBP (−3.7 mmHg [−4.9; −2.5] vs. −1.4 mmHg [−3.1; 0.2], p < 0.028) after 12 months. Compared to CON, INT showed a pronounced reduction in resting HR and PWV after 6 months but both lost significance after 12 months. Changes in SBP, DBP, and PWV were significantly associated positively with changes in body weight and fat mass (all p < 0.05) and resting HR correlated positively with fasting insulin (p < 0.001) after 12 months. Combining a lifestyle intervention with a high-protein and low-glycemic formula diet improves hemodynamic parameters to a greater extent than lifestyle intervention alone in high-risk individuals with overweight and obesity.

Meal replacement by formula diet reduces weight more than a lifestyle intervention alone in patients with overweight or obesity and accompanied cardiovascular risk factors-the ACOORH trial.

BACKGROUND: As formula diets have demonstrated to be effective in reducing weight, we hypothesised that in patients with overweight or obesity and accompanied cardiovascular risk factors, combining a liquid formula diet with a lifestyle intervention is superior in reducing weight and improving cardiovascular risk factors than lifestyle intervention alone. METHODS: In this multicenter RCT 463 participants with overweight or obesity (BMI: 27-35 kg/m²; at least one additional co-morbidity of the metabolic syndrome) were randomised (1:2) into either a control group with lifestyle intervention only (CON, n = 155) or a lifestyle intervention group including a liquid meal replacement (INT, n = 308). Both groups used telemonitoring devices (scales and pedometers), received information on healthy diet and were instructed to increase physical activity. Telemonitoring devices automatically transferred data into a personalised online portal and acquired data were discussed. INT obtained a liquid meal replacement substituting three meals/day (~1200 kcal) within the first week. During weeks 2-4, participants replaced two meals/day and during weeks 5-26 only one meal/day was substituted (1300-1500 kcal/day). Follow-up was conducted after 52 weeks. Intention-to-treat analyses were performed. Primary outcome was weight change. Secondary outcomes comprised changes in cardiometabolic risk factors including body composition and laboratory parameters. RESULTS: From the starting cohort 360 (78%, INT: n = 244; CON: n = 116) and 317 (68%, INT: n = 216; CON: n = 101) participants completed the 26-weeks intervention phase and the 52-weeks follow-up. The estimated treatment difference (ETD) between both groups was -3.2 kg [-4.0; -2.5] (P < 0.001) after 12 weeks and -1.8 kg [-2.8; -0.8] (P < 0.001) after 52 weeks. CONCLUSIONS: A low-intensity lifestyle intervention combined with a liquid meal replacement is superior regarding weight reduction and improvement of cardiovascular risk factors than lifestyle intervention alone.

Epidemiological and economic burden of metabolic syndrome and its consequences in patients with hypertension in Germany, Spain and Italy; a prevalence-based model.

BACKGROUND: The presence of metabolic syndrome in patients with hypertension significantly increases the risk of cardiovascular disease, type 2 diabetes and mortality. Our aim is to estimate the epidemiological and economic burden to the health service of metabolic syndrome in patients with hypertension in three European countries in 2008 and 2020. METHODS: An age, sex and risk group structured prevalence based cost of illness model was developed using the United States Adult Treatment Panel III of the National Cholesterol Education Program criteria to define metabolic syndrome. Data sources included published information and public use databases on disease prevalence, incidence of cardiovascular events, prevalence of type 2 diabetes, treatment patterns and cost of management in Germany, Spain and Italy. RESULTS: The prevalence of hypertension with metabolic syndrome in the general population of Germany, Spain and Italy was 36%, 11% and 10% respectively. In subjects with hypertension 61%, 22% and 21% also had metabolic syndrome. Incident cardiovascular events and attributable mortality were around two fold higher in subjects with metabolic syndrome and prevalence of type 2 diabetes was around six-fold higher. The economic burden to the health service of metabolic syndrome in patients with hypertension was been estimated at €24,427, €1,900 and €4,877 million in Germany, Spain and Italy and forecast to rise by 59%, 179% and 157% respectively by 2020. The largest components of costs included the management of prevalent type 2 diabetes and incident cardiovascular events. Mean annual costs per hypertensive patient were around three-fold higher in subjects with metabolic syndrome compared to those without and rose incrementally with the additional number of metabolic syndrome components present. CONCLUSION: The presence of metabolic syndrome in patients with hypertension significantly inflates economic burden and costs are likely to increase in the future due to an aging population and an increase in the prevalence of components of metabolic syndrome.

Prediabetes Conversion to Normoglycemia Is Superior Adding a Low-Carbohydrate and Energy Deficit Formula Diet to Lifestyle Intervention-A 12-Month Subanalysis of the ACOORH Trial.

Lifestyle interventions have been shown to reverse hyperglycemia to normoglycemia. However, these effects are not long-lasting and are accompanied with high dropout rates. As formula diets have been shown to be simple in usage and effective in improving glycemic control, we hypothesised that adding a low-carbohydrate and energy deficit formula diet to a low-intensity lifestyle intervention is superior in reversing prediabetes compared with lifestyle intervention alone. In this predefined subanalysis of an international, multicenter randomised controlled trial (Almased Concept against Overweight and Obesity and Related Health Risk (ACOORH) study (ID DRKS00006811)), 141 persons with prediabetes were randomised (1:2) into either a control group with lifestyle intervention only (CON, n = 45) or a lifestyle intervention group accompanied with a formula diet (INT, n = 96). Both groups were equipped with telemonitoring devices. INT received a low-carbohydrate formula diet substituting three meals/day (~1200 kcal/day) within the first week, two meals/day during week 2-4, and one meal/day during week 5-26 (1300-1500 kcal/day). Follow-up was performed after 52 weeks and 105 participants (75%, INT: n = 74; CON: n = 31) finished the 26-week intervention phase. Follow-up data after 52 weeks were available from 93 participants (66%, INT: n = 65; CON: n = 28). Compared with CON, significantly more INT participants converted to normoglycemia after 52 weeks (50% vs. 31%; p < 0.05). The risk reduction led to a number-needed-to-treat of 5.3 for INT. Lifestyle intervention with a low-carbohydrate formula diet reduces prediabetes prevalence stronger than lifestyle intervention alone and is effective for type 2 diabetes prevention.

Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study.

BACKGROUND: Current guidelines for the treatment of hypertension do not provide specific recommendations for obese hypertensive patients. To identify an optimal treatment regimen for obese hypertensive patients, we studied the interactions between a drug-based weight loss approach by sibutramine and different antihypertensive drug regimens. METHODS AND RESULTS: This was a prospective, 16-week double-blind placebo-controlled randomized multicenter study in 171 obese hypertensive patients. After a 2-week run-in period, patients receiving 1 of the 3 antihypertensive combination therapies (felodipine 5 mg/ramipril 5 mg [n=57], verapamil 180 mg/trandolapril 2 mg [n=55], or metoprolol succinate 95 mg/hydrochlorothiazide 12.5 mg [metoprolol/hydrochlorothiazide; n=59]) were assigned randomly to sibutramine (15 mg) or placebo. Sibutramine treatment resulted in a significantly greater decrease in body weight, body mass index, and waist circumference and a significant increase in diastolic blood pressure during 24-hour blood pressure monitoring compared with placebo treatment. Sibutramine-induced weight loss and reduction of visceral obesity were markedly attenuated in the metoprolol/hydrochlorothiazide group compared with the other groups. Consistently, improvement in glucose tolerance and hypertriglyceridemia by sibutramine was abrogated in the cohort treated with metoprolol/hydrochlorothiazide compared with the other groups. CONCLUSIONS: The present study demonstrates for the first time that an antihypertensive combination therapy regimen with angiotensin-converting enzyme inhibitors and calcium channel blockers is more advantageous than a beta-blocker/diuretic-based regimen in supporting the weight-reducing actions and concomitant metabolic changes induced by sibutramine in obese hypertensive patients. These data may help to develop future comprehensive treatment strategies and guidelines for this high-risk patient population.

An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole.

OBJECTIVE: The purpose of this study was to determine the efficacy of standard treatment with oral metronidazole in the eradication of the bacterial vaginosis biofilm. STUDY DESIGN: We conducted an interventional follow-up study in which 18 patients with bacterial vaginosis were treated with oral metronidazole during 1 week and subsequently had a single random follow-up assessment at 1-week intervals, up to 5 weeks, with 3 patients representing each point in time. Follow-up assessment included conventional scoring of the vaginal microflora and determination of bacterial biofilm characteristics on a vaginal biopsy through bacterial 16/23S recombinant DNA-based fluorescence in-situ hybridization. RESULTS: Although all patients recovered, we consistently observed the resurgence with treatment cessation of a dense and active bacterial biofilm on the vaginal mucosa, primarily consisting of Gardnerella vaginalis and Atopobium vaginae. CONCLUSION: A large reservoir of the core bacteria to bacterial vaginosis persists as a biofilm after metronidazole treatment.

Single-Pill Triple Fixed Dose Combination Therapy with Single Component Drug Monitoring in Treatment-Resistant Hypertension: A Pilot Study.

BACKGROUND: Single-pill fixed dose combination (FDC) therapies are widely used in the treatment of arterial hypertension. OBJECTIVE: This pilot study aimed to evaluate the effects of a FDC therapy combined with therapeutic drug monitoring (TDM) on blood pressure (BP) in patients with treatment resistant hypertension. METHOD: The study population included patients with suspected treatment-resistant hypertension during treatment with at least 3 antihypertensive drugs. We evaluated the effect of switching all patients to a regime including a single-pill triple FDC containing olmesartan, amlodipine and hydrochlorothiazide. Adherence was evaluated by measuring serum concentrations of amlodipine in a single-blinded fashion. RESULTS: We enrolled 13 patients (mean age 57.2±9.1 years, 8 males) with resistant hypertension (office systolic and diastolic BP 158.3±17.3 and 94.8±11.1 mmHg); mean use of antihypertensive drugs was 3.8±1.1. Medication intake of FDC was confirmed in all patients at 18 weeks. Systolic and diastolic office BP were significantly lower (-22.8 and -13.6 mmHg) after 18 weeks of treatment with triple FDC (135.5±20.1 and 81.2±6.3 mmHg, p<0.01, respectively); mean use of antihypertensive drugs was 3.8±0.9. In 9 patients with 24-h ambulatory BP monitoring (ABPM) both at baseline and after 18 weeks, 24-h mean arterial pressure decreased (-9.3 mmHg, p=0.055). Overall, 9 (69%) patients achieved BP control in office BP and 4 (31%) in 24-h ABPM. CONCLUSION: Our results support the use of single-pill triple FDC therapy in combination with TDM for the management of patients with suspected treatment-resistant hypertension and further testing in clinical studies.

Effects of the angiotensin II type 1 receptor antagonist telmisartan on monocyte adhesion and activation in patients with essential hypertension.

Circulating monocytes from hypertensive patients show elevated secretion patterns of pro-inflammatory cytokines, an increased expression of adhesion molecules, and an increased adhesion to vascular endothelial cells. We tested the hypothesis that telmisartan, an angiotensin II type 1 (AT(1)) receptor antagonist, reduces the activation of circulating monocytes from hypertensive patients and diminishes the monocyte-endothelial cell adhesion. Monocytes of 20 hypertensive patients and 20 normotensive controls were isolated by density gradient centrifugation and Dynabeads, and the monocyte adhesion to human aortic endothelial cell monolayers was measured by adhesion assays. To characterize monocyte activation we assessed the expression of activity-related cell surface markers that are also involved in monocyte adhesion to endothelial cells, such as CD11a/b and CD54, as well as the chemokine receptors CCR1, CCR2 and CCR5 before and after telmisartan therapy using flow cytometry. Spontaneous adhesion of monocytes from hypertensive patients and the adhesion after stimulation with angiotensin II were significantly increased compared with those in normotensive controls (p<0.05). Treatment of hypertensive patients with the AT(1) receptor antagonist telmisartan significantly diminished the adhesion of circulating monocytes to human endothelial cells (p=0.02) despite the increase in the expressions of CD11b, CD54 and CCR5 after telmisartan therapy. Reducing monocyte adhesion may be a novel beneficial effect of the AT(1) receptor antagonist telmisartan helping to prevent vascular alterations in hypertension. The mechanism of action remains to be elucidated, since reduction in monocyte adhesion was not attributable to changes in adhesion molecule expression.

[Cardiometabolic high risk patients with abdominal obesity. Frequency and risk factor profile in primary care]. / Kardiometabolische Hochrisikopatienten bei abdominalerAdipositas. Häufigkeit und Risikofaktorenprofil in der niedergelassenen Praxis.

OBJECTIVE: A large abdominal girth is a measure for abdominal obesity that is associated with many cardiometabolic risk factors and ultimately with an unfavourable prognosis. In this context, the objective of this survey was, to document the frequency of concomitant cardiometabolic risk factors such as diabetes and dyslipidaemia in primary care, to quantify the cross-section of all three risk factors and to investigate the medical care situation of the patients. METHODS: For the survey, an open surveillance study design was chosen. Privately practicing physicians of different specializations documented the comorbidities and the medications taken in patients with abdominal obesity (based on waist circumference [men > or = 102, women > or = 88 cm]). The data were evaluated qualitatively and assessed exploratively. RESULTS: A total of 3,945 participating doctors documented 53,147 patients with large abdominal girth. In 71% of the cases, these patients also had type 2 diabetes mellitus. In 76% of the cases, the patients had dyslipidaemia and in 35% of the cases, all three risk factors occurred concomitantly. Taking multiple medications such as antihypertensives, antidiabetic and lipid-lowering agents and thrombocyte aggregation inhibitors, was common. However, the target values, for example, for blood sugar (HbA1c < 6.5 or < 7.0%) frequently could not be achieved with the conventional strategies. CONCLUSION: Abdominal obesity (based on abdominal girth) is an important risk factor for cardiovascular disease. It often occurs together with type 2 diabetes mellitus, (atherogenic) dyslipidaemia and arterial hypertension. Available therapeutic strategies are not always sufficient for achieving the recommended metabolic values.

Efficacy and Safety of Cathine (Nor-Pseudoephedrine) in the Treatment of Obesity: A Randomized Dose-Finding Study.

OBJECTIVE: To investigate the efficacy and safety of increasing doses of cathine (nor-pseudoephedrine) as a weight-lowering agent in patients with obesity. METHODS: Overweight and obese patients (n = 241, mean BMI 34.6 ± 3.4 kg/m²) were randomly allocated to one of three doses of cathine (16 mg, 32 mg, 53.3 mg) or placebo in addition to a multimodal lifestyle intervention program in a multicenter, double-blind, controlled, dose-finding study for 24 weeks. Primary outcome was weight loss. RESULTS: Treatment with the 3 doses of cathine resulted in a significantly greater weight loss compared to placebo over 24 weeks: 6.5 ± 4.2 kg for 16 mg cathine, 6.2 ± 4.7 kg for 32 mg cathine, and 9.1 ± 5.4 kg for 53.3 mg cathine versus 2.4 ± 4.4 kg for placebo (each p < 0.01, ANCOVA). The percentage of patients losing > 5% / >10% of initial body weight was significantly greater for all doses of cathine than for placebo (each p < 0.01, chi-square test). Heart rate increased dose-dependently (by 1.2 bpm under 16 mg, 5.8 bpm under 32 mg, and 6.2 bpm under 53.3 mg cathine), but no suspected unexpected serious adverse reactions were noted. The overall dropout rate was 24.9%, with the highest rate in the placebo group (42.3%). CONCLUSION: Cathine appears to be an effective weight-lowering agent for adjunct treatment of obesity, but additional clinical studies on its efficacy and safety are required.

Adding Hydrochlorothiazide to Olmesartan/Amlodipine Increases Efficacy in Patients With Inadequate Blood Pressure Control on Dual-Combination Therapy.

This randomized, parallel-group study in patients inadequately controlled on olmesartan medoxomil/amlodipine (OLM/AML) 40/10 mg assessed the effects of adding hydrochlorothiazide (HCTZ) 12.5 mg and 25 mg, using seated blood pressure (SeBP) measurements and ambulatory blood pressure (BP) monitoring. Enrolled patients were screened and tapered off of therapy if required. All patients received OLM/AML 40/10 mg and those with mean seated BP (SeBP) ≥140/90 mm Hg after 8 weeks (n=808) were randomized (1:1:1) to continue with OLM/AML 40/10 mg or receive OLM/AML/HCTZ 40/10/12.5 or 40/10/25 mg for a further 8 weeks. The primary endpoint was the change in seated diastolic BP (SeDBP) from the start to the end of the randomized treatment period. The addition of HCTZ 25 mg significantly reduced SeDBP (-2.8 mm Hg; P<.0001), lowered seated systolic BP (SeSBP) and ambulatory DBP and SBP, and improved BP goal rates. In patients uncontrolled on OLM/AML 40/10 mg, adding HCTZ led to further BP reductions, particularly in ambulatory BP.

Agonistic AT(1) receptor autoantibodies and monocyte stimulation in hypertensive patients.

BACKGROUND: Agonistic AT(1) receptor autoantibodies (AT(1)-AA) have been described in hypertensive and preeclamptic patients. Furthermore, monocytes are activated in hypertensive patients. We investigated and compared the ability of angiotensin II (Ang II) and AT(1)-AA to stimulate monocytes from hypertensive and normotensive persons. The adhesiveness of the monocytes to endothelial cell layers, tissue factor expression, and chemiluminescence were determined. METHODS: Blood samples were obtained from 17 patients with essential hypertension and from 20 normotensive subjects. Peripheral blood monocytes were isolated by Dynabeads and used in adhesion experiments. Adherence assays, Western blotting, and reactive oxygen species release by chemiluminescence were done. RESULTS: Monocyte adhesion to human aortic or umbilical vein endothelial cell layers was significantly higher after stimulation with AT(1)-AA, compared to Ang II or no stimulation. The effect was blocked with tissue factor antibody or epitope peptide preincubation. Eposartan was partially effective in blocking the effects. Western blotting after AT(1)-AA or Ang II stimulation showed that the monocytes expressed tissue factor. The AT(1)-AA and Ang II induced significantly higher chemiluminescence in monocytes from hypertensive than control subjects. Endothelial cells, on the other hand, showed much less chemiluminescence. CONCLUSIONS: These data show that monocytes can be stimulated by AT(1)-AA and Ang II to adhere, produce tissue factor, and probably reactive oxygen species. They underscore the importance of monocyte activation in hypertensive patients. The relevance of AT(1)-AA in hypertension will require further studies.

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.

Impact of socio-economic factors on the long-term effectiveness of antihypertensive treatment with an angiotensin II receptor blocker: an observational study.

OBJECTIVE: To investigate the role of socio-economic factors on the therapeutic effectiveness of and therapeutic adherence to the angiotensin II receptor blocker (ARB) olmesartan (OM) alone or in combination with hydrochlorothiazide in the treatment of arterial hypertension. RESEARCH DESIGN AND METHODS: In a multi-center, open-label, prospective and long-term observational study, data from hypertensive patients treated with OM were analyzed at baseline, month 3 and month 12 within the context of patients' socio-economic status (SES), determined using pre-defined criteria by physicians in outpatient practices and including multivariate analysis. RESULTS: Overall, 7724 patients were assigned to three subgroups representing low, medium and high socio-economic status. Baseline conditions differed significantly between the subgroups. Patients of low SES had worse nutritional habits, less physical activity and more concomitant medication compared to patients of high SES. Cardiovascular risk factors were more common in the low SES group as were concomitant diseases such as heart failure, coronary heart disease, atherosclerosis and renal failure. OM therapy led to a significant decrease in blood pressure (23.0/11.6 mmHg) in all patients. The blood pressure target of <140/90 mmHg was achieved in about 70% of the documented population. Effectiveness was comparable between patients with low, medium or high SES. Treatment adherence was high in the overall population with only minor differences between the subgroups. In total the incidence of adverse events (AEs) was 1.6% documented in 98 patents (1.3%) during the course of the study. Of this total number only 1.0% was related to the drug, matching the percentage expressed in the Summary of Product Characteristics (SmPC). CONCLUSIONS: The ARB OM is effective and well tolerated in all patients, irrespective of their socio-economic status. The risk status and the established cardiovascular disease of hypertensive patients are strongly influenced by the SES. To validate these interesting data a randomized controlled trial is needed.

Endothelial progenitor cells in systemic lupus erythematosus.

BACKGROUND AND AIM: Systemic lupus erythematosus (SLE) is an autoimmune-mediated disease, characterized by inflammation of small arteries and arterioles. Patients with SLE suffer from a 17-fold higher risk for developing atherosclerosis than healthy individuals. Endothelial progenitor cells (EPCs) have been shown to be critically involved in microvascular repair under both physiological and pathological conditions. The aim of the present study was to analyze EPC regeneration and mobilization in SLE patients with variable disease activity and undergoing different treatment regimens. METHODS: Forty-eight patients with SLE were analyzed. Healthy, age- and sex-matched individuals served as controls. Total circulating EPCs were enumerated by FACS analysis, and regenerative activity of the cells was analyzed by a colony-forming assay. Vasomodulatory mediators were quantified by ELISA. RESULTS: SLE patients did not show lower or higher percentages of total circulating EPCs, but they displayed significantly lower colony numbers as compared with healthy controls, indicating impaired EPC regeneration and mobilization. Low and high disease activity were associated with decreased EPC regeneration, while moderate disease activity was not. Hypertension and, to some extent, renal involvement were associated with reduced colony formation. Patients not receiving hydroxychloroquine (HCQ) treatment and those undergoing glucocorticoid therapy showed impaired EPC regeneration as well. CONCLUSIONS: SLE patients suffer from both defective regeneration and mobilization of EPCs. Such an impairment of the EPC system, as one key regulatory element in the process of vasorepair, could potentially promote microvascular damage in SLE. Long-term glucocorticoid therapy may further suppress the EPC system, while HCQ may prevent regeneration of the cells.

Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines.

BACKGROUND: Melatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients. METHODS: Patients (n=605, mean age 56.2±9.4years, 82.3% male) with arterial hypertension and cardiac ejection fraction (EF) ≥40% were studied. Cardiac parameters were assessed by echocardiography. RESULTS: The cohort comprised subjects with coronary heart disease (73.1%) and myocardial infarction (48.1%) with a mean EF of 63.7±8.9%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4mmHg, 95% confidence interval (CI): 0.3 to 4.5mmHg, p=0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8% (CI: 0.45 to 3.14%) in carriers versus non-carriers (p=0.009). CONCLUSION: Genetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target.

Safety and efficacy of olmesartan: an observational pooled-analysis of 156,682 hypertensive patients.

BACKGROUND: Angiotensin type 1 receptor blockers are recommended for first-line antihypertensive treatment. METHODS: We performed a pooled-analysis of 20 post-authorization surveys of olmesartan involving 156,682 hypertensive patients. Olmesartan was used as monotherapy or in combination with other antihypertensive drugs, for example, hydrochlorothiazide. OBJECTIVES: We assessed the safety of olmesartan by monitoring adverse drug reactions (ADRs). The number of patients achieving systolic and diastolic blood pressure (BP) targets (< 140/90 mmHg in the overall population, < 130/80 mmHg in high-risk patients) or responding to treatment (BP decrease of ≥ 20/10 mmHg) was also determined. RESULTS: In all, 43.8% of patients received olmesartan monotherapy, 29% olmesartan with hydrochlorothiazide and 27.2% olmesartan in combination with other antihypertensives. The frequency of ADRs was 0.4% and not altered by dose, age ≥ 65 years or presence of co-morbidities. About 90% of patients were responders. Blood pressure targets were achieved in 52.8 and 35.7% of patients without risk factors and in the overall cohort, but only in 8.1 and 27.5% of patients with renal dysfunction or taking NSAIDs. CONCLUSION: Olmesartan was very well tolerated. Responder rates to olmesartan were high, although BP targets were only achieved in a minority of patients at high risk, with renal dysfunction or taking NSAIDs.