Csaba Farsang

Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document.

Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit

Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document

Reappraisal of European guid elines on hypertension management: a European Society of Hypertension Task Force document Giuseppe Mancia, Stephane Laurent, Enrico Agabiti-Rosei, Ettore Ambrosioni, Michel Burnier, Mark J. Caulfield, Renata Cifkova, Denis Clement, Antonio Coca, Anna Dominiczak, Serap Erdine, Robert Fagard, Csaba Farsang, Guido Grassi, Hermann Haller, Anthony Heagerty, Sverre E. Kjeldsen, Wolfgang Kiowski, Jean Michel Mallion, Athanasios Manolis, Krzysztof Narkiewicz, Peter Nilsson, Michael H. Olsen, Karl Heinz Rahn, Josep Redon, Jose Rodicio, Luis Ruilope, Roland E. Schmieder, Harry A.J. Struijker-Boudier, Pieter A. van Zwieten, Margus Viigimaa and Alberto Zanchetti

Study on COgnition and Prognosis in the Elderly (SCOPE)

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by <10 mmHg since the randomization visit, or DBP is >85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged.

Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT

To investigate the effect of valsartan in the Valsartan‐Heart Failure Trial (Val‐HeFT) when added to angiotensin‐converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF).

Increased prevalence of metabolic syndrome in uncontrolled hypertension across Europe: the Global Cardiometabolic Risk Profile in Patients with hypertension disease survey.

Objectives The Global Cardiometabolic Risk Profile in Patients with hypertension disease survey investigated the cardiometabolic risk profile in adult outpatients with hypertension in Europe according to the control of blood pressure (BP) as defined in the European Society of Hypertension and of the European Society of Cardiology (ESH/ESC) guidelines. Methods Data on BP control and cardiometabolic risk factors were collected for 3370 patients with hypertension in 12 European countries. Prevalence was analyzed according to BP status and ATP III criteria for metabolic syndrome. Results BP was controlled (BP < 140/90 mmHg for nondiabetic patients; BP < 130/80 mmHg for diabetic patients) in 28.1% of patients. Patients with uncontrolled BP had significantly higher mean weight, BMI, waist circumference, fasting blood glucose, total cholesterol and triglycerides and high-density lipoprotein cholesterol levels were significantly lower (women only) compared with patients with controlled BP (P < 0.05). The prevalence of metabolic syndrome and type 2 diabetes was also significantly higher in patients with uncontrolled BP compared with controlled BP (P < 0.001) (metabolic syndrome: 66.5 versus 35.5%; diabetes 41.1 versus 9.8%, respectively). 95.3% of patients with both metabolic syndrome and type 2 diabetes had uncontrolled BP. In a multivariate analysis, diabetes and metabolic syndrome were found to be associated with a high risk of poor BP control: odds ratio, 2.56 (metabolic syndrome); 5.16 (diabetes). Conclusion In this European study, fewer than one third of treated hypertensive patients had controlled BP. Metabolic syndrome and diabetes were important characteristics associated with poor BP control. Thus, more focus is needed on controlling hypertension in people with high cardiometabolic risk and diabetes.

Increased Soluble Fas Plasma Levels in Subjects at High Cardiovascular Risk Atorvastatin on Inflammatory Markers (AIM) Study, a Substudy of ACTFAST

Objectives—Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment. Methods and Results—ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk >20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides ≤600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL. Conclusions—sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.

Valsartan in combination with lisinopril versus the respective high dose monotherapies in hypertensive patients with microalbuminuria: The VALERIA trial

Objectives Microalbuminuria is known as an independent predictor for stroke, myocardial infarction, and death. The purpose of the VALERIA trial was a comparison of the efficacy and safety of combination therapy of valsartan and lisinopril with valsartan and lisinopril high-dose monotherapy in patients with hypertension and microalbuminuria. Methods This was a randomized, double-blind, interventional, parallel-group study. After a washout/placebo- run-in phase of 3 weeks, 133 patients were randomized to treatment (1: 1:1) with either lisinopril 40 mg, valsartan 320 mg, or a combination of valsartan/lisinopril 320/20 mg for 30 weeks. Results At baseline, the urine albumin creatinine ratio was similar for the three treatment groups (geometric means, lisinopril 9.6 mg/mmol, valsartan 9.1 mg/mmol, and valsartan/lisinopril 9.5 mg/mmol). After 30 weeks of treatment, the geometric mean urine albumin creatinine ratio had decreased in all three groups by 41, 51, and 62% to 5.7 mg/mmol (lisinopril), 4.5 mg/mmol (valsartan), and 3.6 mg/mmol (valsartan/lisinopril). The decrease for valsartan/lisinopril was statistically significantly greater compared with lisinopril [adjusted ratio 60%, confidence interval (38–94%), P = 0.029]. Normalization of microalbuminuria was greatest with valsartan and valsartan/lisinopril (lisinopril 17%, valsartan 31%, and valsartan/lisinopril 38% of patients) and was statistically significant for lisinopril in contrast with valsartan/lisinopril (P = 0.034). Differences in blood pressure reduction between the groups were not statistically significant. All treatments were safe and well tolerated. Conclusion The combination of valsartan and lisinopril provided a significantly better reduction of urine albumin creatinine ratio and more than doubled the rate of patients with normalized urine albumin creatinine ratio compared with lisinopril alone. All treatments were safe and well tolerated.

Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk

Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension

Objective To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the β-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment. Methods A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160–205 mmHg, and a sitting diastolic blood pressure (SiDBP) <90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP ⩾ 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. Results Similar significant reductions in SiSBPs (mean ± SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 ± 10.3 and 173.5 ± 10.7 mmHg at baseline to 149.0 ± 15.5 and 148.2 ± 15.3 mmHg after 16 weeks of losartan or atenolol treatment, respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P = 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029). Conclusion It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.

Blood pressure control and components of the metabolic syndrome: the GOOD survey

BackgroundThe GOOD (Global Cardiometabolic Risk Profile in Patients with Hypertension Disease) survey showed that blood pressure control was significantly worse in hypertensive patients with metabolic syndrome and/or diabetes mellitus than in those with essential hypertension only. This analysis aimed to investigate which components of the metabolic syndrome are primarily associated with poor blood pressure control.MethodsThe GOOD survey was designed as an observational cross-sectional survey in 12 European countries to assess the cardiometabolic risk profile in patients with essential hypertension. Investigators were randomly selected from a list of general practitioners (70% of investigators) and a list of specialists such as internists, cardiologists and hypertension specialists (30% of investigators). Data from 3,280 outpatients with hypertension, aged at least 30 years who were receiving antihypertensive treatment or had newly diagnosed hypertension according to the European Society of Hypertension and the European Society of Cardiology criteria, were included in the analyses. Blood pressure control, body mass index (BMI), waist circumference, serum triglycerides, total and high density lipoprotein (HDL) cholesterol measurements were compared in patients with diabetes mellitus and metabolic syndrome, with diabetes mellitus only, with metabolic syndrome only, and with neither metabolic syndrome nor diabetes mellitus.ResultsThe highest blood pressure values were found in patients with metabolic syndrome with or without diabetes mellitus. Blood pressure was significantly lower in patients with diabetes mellitus only. The highest BMI, waist circumference and serum triglycerides, and the lowest HDL cholesterol levels among the groups studied occurred in patients with metabolic syndrome, either with or without diabetes mellitus.ConclusionAmong the components of the metabolic syndrome, it is not impaired glucose tolerance which is associated with the poor response to antihypertensive treatment. Instead, visceral obesity and dyslipidemia components of the metabolic syndrome, i.e. hypertriglyceridemia and low HDL cholesterol levels, are associated with resistance to antihypertensive treatment.