Andrzej Tykarski

Valsartan/hydrochlorothiazide is effective in hypertensive patients inadequately controlled by valsartan monotherapy.

Objective: This double-blind parallel-group randomized trial compared the efficacy and safety of fixed combination valsartan 160 mg/hydrochlorothiazide 12.5 mg (Val 160/HCTZ 12.5) once daily (o.d.) and Val 160/hydrochlorothiazide 25 mg (Val 160/HCTZ 25) o.d. vs Val 160 o.d. monotherapy in patients with mild-to-moderate essential hypertension not adequately controlled with valsartan monotherapy. Method: A total of 2002 patients whose BP was inadequately controlled with 4 weeks of Val 160 mg o.d. monotherapy were randomized to treatment for 8 weeks with Val 160 (n = 666), Val 160/HCTZ 12.5 (n = 670) or Val 160/HCTZ 25 (n = 666). Results: Active treatment significantly reduced BP in all groups over the 12 weeks of the study (p < 0.001). The greatest reductions were achieved with Val 160/HCTZ 25. Reductions were 10.8, 12.8 and 14.2 mmHg (sitting diastolic blood pressure) and 15.7, 19.4 and 21.8 mmHg (sitting systolic blood pressure), for the Val 160, Val 160/HCTZ 12.5 and Val 160/HCTZ 25 groups, respectively. Responder rates were high in all groups (49%, 62% and 68%). In elderly patients (≥65 years) responder rates of 70% were achieved with Val 160/HCTZ 25. All treatments were well tolerated, in all patient groups. Conclusions: The combination of Val 160 plus HCTZ 12.5 or HCTZ 25 provides effective and well-tolerated treatment in patients inadequately controlled after 4 weeks of monotherapy. In elderly patients a responder rate of 70% was achieved with Val 160/HCTZ 25.

Main results of the Ouabain and Adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin

BackgroundThe Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans.MethodsOASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed).ResultsAmong 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo.ConclusionsIn 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose.Trial RegistrationClinicalTrials (NCT): NCT00415038

Socio-demographic and lifestyle correlates of commuting activity in Poland.

OBJECTIVES The aim of this study is to analyse the epidemiology of active transportation and to investigate the relationship between commuting physical activity (PA) and socio-demographic and lifestyle characteristics in Poland. METHODS A cross sectional analysis was conducted among 7280 randomly selected individuals (3747 men and 3533 women) aged 20-74 years participating in the National Multicentre Health Survey WOBASZ (2002-2005). Socio-demographic, smoking and physical activity details were assessed by an interviewer-administered questionnaire. RESULTS Only 36% of the participants (30% men and 42% of women) are active commuters. Moreover, 55.4% of them spend less than 15 min/day on walking or cycling. The highest risk of commuting inactivity was noticed among residents of large urban settings, with university education, the highest income and low occupational PA in both genders. Smoking and leisure-time PA were not significantly associated with commuting activity. CONCLUSIONS Active commuting is not common in Poland. There are several differences in commuting patterns as compared with the US or Western European populations. Due to important differences between various socio-demographic groups, future interventions should be specific for the targeted subpopulations.

Commuting physical activity and prevalence of metabolic disorders in Poland

OBJECTIVES The aim of this study was to examine the relationship between walking or cycling to work and prevalence of metabolic syndrome (MetS) and its components. METHODS Cross-sectional analysis of 6401 randomly selected individuals (3297 men and 3104 women) aged 20-74 years, who participated in the National Multicentre Health Survey WOBASZ, Poland (2002-2005). Commuting physical activity (PA) was assessed by asking about type and time spent on transportation to/from work using an interviewer-administered questionnaire. Weight, height, waist circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), triglycerides (TG) and high-density cholesterol, (HDL-C) were measured by standard methods. MetS was defined according to the NCEP-ATP III and IDF criteria. RESULTS Active commuting was associated with decreased likelihood of abdominal obesity (WC≥94 cm), lower HDL-C and elevated TG in men and abdominal obesity (WC≥80 cm) in women. In a subgroup of postmenopausal women (n=317) active commuting was favourably associated with abdominal obesity, low HDL-C and elevated FPG. Prevalence of MetS was significantly lower among those who spent above 30 min/day daily on walking/cycling to work than among other gender subgroups. CONCLUSION Increasing of commuting PA level may have an important influence on reducing the prevalence of metabolic disorders.

Smoking status, the menopausal transition, and metabolic syndrome in women.

ObjectiveData on the relationship between tobacco use and metabolic risk among women with regard to their menopause status are scarce. This study assessed the prevalence of metabolic disorders in relation to smoking status in premenopausal and postmenopausal women. MethodsA cross-sectional analysis of 7,462 randomly selected women aged 20 to 74 years who are participating in the WOBASZ (Polish National Multicentre Health Survey) was carried out. Lifestyle and menopause status details were collected via an interviewer-administered questionnaire. Weight, height, waist circumference, blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels were measured by standard methods. Metabolic syndrome (MetS) was defined according to the International Diabetes Federation criteria. ResultsThe prevalence of MetS was 3.3-fold higher among postmenopausal than premenopausal women. Regardless of menopause status, the prevalence of central obesity was significantly higher among never and past smokers versus current smokers (P < 0.001). Past smoking was associated with a significantly higher probability of elevated blood pressure, fasting plasma glucose, and MetS (P < 0.05). However, premenopausal never and past smokers had a substantially lower prevalence of decreased HDL-C than did current smokers. Among postmenopausal nonsmoking women, high levels of leisure time and commuting physical activity were associated with a reduced likelihood of MetS (P < 0.01). Making an additional adjustment for calorie consumption did not substantially influence the results. ConclusionsExcept for HDL-C level, not smoking is associated with an unfavorable metabolic profile in women, regardless of menopause status. High level of physical activity may reduce the prevalence of MetS among never and past smokers after the menopausal transition.

Characterization of insomnia in patients with essential hypertension.

Introduction. Insomnia may increase risk of cardiovascular events. There is little data available reporting the prevalence and clinical relevance of insomnia in patients with essential hypertension. Therefore, the aim of the study was to investigate the relationship between insomnia and different clinical and biochemical parameters in essential hypertension patients. Methods. Four hundred and thirty‐two patients (mean age: 47±13 years; 253 male, 179 female) with essential hypertension were screened for insomnia using the Athens Insomnia Scale (AIS). Several variables including age, sex, known duration of hypertension, body mass index, creatinine, left ventricular mass index, coexisting disorders, smoking status and alcohol use were analysed. Twenty‐four‐hour ambulatory blood pressure measurements (ABPM) were performed. Results. Among patients included in the study, 207 subjects (mean age: 49±13 years; 47.9%) had an AIS score of 15 or higher and were identified as insomniacs. Insomnia was more frequent in women than in men (60.9% vs 38.7%, p<0.001) and was reported more frequently in patients with coronary artery disease. Subjects with insomnia were older and had longer duration of hypertension. There were no differences between insomniacs and non‐insomniacs in ABPM parameters. A relationship was found between the number of antihypertensive drugs and insomnia frequency. There were correlations between AIS score and age (r = 0.21; p<0.001) and duration of hypertension (r = 0.22; p<0.001). In the sub‐group of untreated essential hypertension patients, there were negative correlations between AIS score and night fall in systolic and diastolic blood pressure. Conclusion. Our results showed that insomnia is common in patients with essential hypertension and indicate an association between insomnia and gender, known duration of hypertension and number of antihypertensive drugs taken. Untreated essential hypertension insomniacs were characterized by less pronounced nocturnal fall in both systolic and diastolic blood pressure compared with non‐insomniacs.

A marked fall in nocturnal blood pressure is associated with the stage of primary open-angle glaucoma in patients with arterial hypertension

Abstract Introduction. The aim of this study was to assess blood flow in the vessels of the eyeball and changes in the optic nerve in patients with arterial hypertension and primary open-angle glaucoma. Material and Methods. The patients were divided into groups: 1 (night blood pressure, BP, fall, NBPF, not more than 10%; non-dippers); 2 (NBPF 10–15%, dippers) and 3 (NBPF>15%; extreme dippers). Results. In the group of dippers and extreme dippers, perfusion pressure was significantly lower than that in the non-dippers group, there was reduced thickness of the nerve fibers and a greater decrease in the visual field. Significant relationships between peak systolic, end-diastolic flow in the ophthalmic and central retinal arteries and night perfusion pressure, thickness of nerve fibers, and a loss of visual field were observed. Conclusion. In patients with glaucoma and well-controlled hypertension, a nocturnal BP fall of more than 10% is associated with a greater visual field defect and greater degeneration of the optic nerve fibers. Low minimum diastolic pressure and the level of nocturnal BP fall, but not the absolute value of average arterial BP at night, should be included in the group of specific risk factors in patients with hypertension and open-angle glaucoma. These findings also suggest avoiding excessive lowering of BP at night in this group.

Effect of allopurinol on blood pressure and aortic compliance in hypertensive patients

Abstract Background. Arterial hypertension is commonly associated with hyperuricemia. Several studies have shown that allopurinol reduces arterial blood pressure in animal models and in adolescent patients with newly diagnosed hypertension. Moreover, allopurinol has shown beneficial effects on endothelial function and arterial wave reflection in contrast to uricosuric agents. Antihypertensive drugs produce different effects on serum uric acid levels. Objective. The aim of the study was to evaluate the influence of allopurinol on blood pressure and aortic compliance in patients with arterial hypertension depending on hypotensive therapy with angiotensin-converting enzyme inhibitor (ACE-I) or thiazide diuretic, hypotensive drugs with distinct effects on serum uric acid levels and conversely, a positive influence on pulse wave velocity (PWV) in the aorta. Material and Methods. Sixty-six patients aged 25–70 (mean age 46.17 ± 10.89) with mild and moderate arterial hypertension diagnosed on the basis of office blood pressure, were studied. They were randomized to antihypertensive therapy on either perindopril (n = 35) or hydrochlorothiazide (n = 31). After 8 weeks of antihypertensive therapy, 150 mg of allopurinol daily was added for the next 8 weeks. Measurement of the serum uric acid level, PWV and 24-h ambulatory blood pressure monitoring (ABPM) were performed at baseline, after 8 weeks antihypertensive therapy and again after the final 8 weeks with the additional allopurinol. Results. No significant changes in systolic (SBP) and diastolic blood pressure (DBP) or ABPM were observed after allopurinol treatment in either of the subgroups receiving ACE-I or thiazide-based antihypertensive therapy. The mean PWV decreased from 10.7 ± 1.4 m/s to 10.0 ± 1.2 m/s (p = 0.00008) in the ACE-I-based therapy subgroup and from 11.5 ±1.7 m/s to 10.4 ± 1.5 m/s (p = 0.00002) in the thiazide-based therapy subgroup after treatment with allopurinol. However, significant correlations were found between PWV changes and the basic PWV (r = −0.52; p < 0.001) or SBP changes (r = 0.29; p < 0.019) after allopurinol treatment. Conclusions. Allopurinol does not produce additional antihypertensive effects in patients with treated arterial hypertension. Allopurinol increases aortic compliance independently of ACE-I or thiazide-based, antihypertensive therapy. However, this effect is significantly dependent on the initial PWV in the aorta and on SBP changes during allopurinol therapy.

Multi-centre National Population Health Examination Survey (WOBASZ II study): assumptions, methods, and implementation.

BACKGROUND Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in developed countries. Despite the progress in diagnostics and treatment, it is expected that CVD will still be the main cause of death worldwide until at least 2030. From 1991 CVD mortality in Poland systematically decreased, but it is still higher than the average in Western Europe. In 2013 CVDs were the cause of 46% of all deaths in Poland (40.9% in men and 51.1% in women) and 26.9% of deaths among persons under 65 years of age. The epidemiologic assessment of prevalence, control and treatment of CVD risk factors, and monitoring of healthy behaviour and morbidity due to diseases like coronary artery disease, hypertension and diabetes is very important for health policy planning. The WOBASZ II is the newest Polish population based survey, performed in 2013-2014 to evaluate prevalence, control, treatment, and morbidity. The study was the continuation of WOBASZ (2003-2005). AIM To describe the goals and methods of the WOBASZ II study and to present the results of the recruitment. METHODS The WOBASZ II study was planned as a cross-sectional survey of a random sample of Polish residents aged over 20 years. The selection, using the National Identity Card Registry of the Ministry of Internal Affairs, was made as a three-stage sampling, stratified according to administrative units (voivodeships), type of urbanisation (commune), and gender. The study protocol consisted of a questionnaire used in face-to-face interviews, physical examination, and blood samples. WOBASZ II was coordinated by the Department of Epidemiology, Cardiovascular Diseases Prevention and Health Promotion of the Institute of Cardiology in Warsaw in cooperation with medical universities in Gdansk, Katowice, Krakow, Lodz, and Poznan. RESULTS Out of 15,120 persons, 1557 persons were not eligible. Out of eligible persons, 6170 (2760 men and 3410 women) were examined (the response rate 45.5%). The highest response rates were observed in Warminsko-Mazurskie (64.2%), Zachodniopomorskie (58.1%), and Kujawsko-Pomorskie (53.1%). CONCLUSIONS The importance of the WOBASZ study for the monitoring of the health state of Polish society, and for the as-sessment of prophylaxis efficiency and treatment of CVD and metabolic diseases, as well as for the evaluation of the actions in the field of health promotion, is difficult to overstate.

Current possibilities of ACE inhibitor and ARB combination in arterial hypertension and its complications

The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in blood pressure regulation and hypertension-related complications. Angiotensin-converting enzyme inhibitors (ACEIs) were the first to be used to block the RAAS and now have many compelling indications in the treatment of hypertension and its cardiovascular and renal complications. Angiotensin II receptor blockers (ARBs), introduced 20 years later, have been shown to be equally as effective as antihypertensive treatment and are also associated with a lower number of side effects. Furthermore, in clinical trials ARBs and ACEIs were associated with comparable benefits for their most typical indications. This was confirmed in the 2007 New European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines for the management of hypertension by comparable specific recommendations for ARB and ACEI treatment. There is sufficient theoretical background and, in some cases, also clinical evidence that combination therapy with ACEIs and ARBs may be more beneficial than monotherapy with either of the groups alone, both in uncomplicated hypertension and with concomitant heart failure or renal dysfunction. However, the combination of ACEI and ARB was not recommended in the ESH/ESC 2007 Guidelines. This may change after the publication of the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) study, the preliminary results of which have just been presented. In heart failure, recent studies have shown that the combination of ACEI and ARB decreases cardiovascular mortality and the number of hospitalizations due to aggravation of heart failure. These results have been reflected in the newest ESC guidelines of the heart failure treatment. Nephroprotective properties of the combination of ACEs and ARBs have been proved both in studies on nondiabetic and diabetic nephropathy. The potential benefits, indications in prespecified groups of patients, the most recent data from clinical trials and latest research regarding dual blockade of RAAS will be reviewed in this article.