Levels of endothelial substances in patients with newly identified hypertension compared with healthy controls.

INTRODUCTION: Endothelial dysfunction occurs at the very beginning of hypertension. The primary goal of our study was to determine plasmatic levels of multiple endothelial substances in otherwise healthy patients with primary hypertension and compare them to healthy individuals. Secondary goals were to determine the change in NOx levels after initiation of treatment and to compare the NOx levels in patients with established resistant hypertension. MATERIALS AND METHODS: 87 consecutive patients were enrolled. In the exploratory cohort of 22 healthy and 28 hypertensive individuals, plasmatic levels of big endotelin-1, asymmetric dimethylarginin, osteopontin, oxidized LDL, 3-nitro-L-tyrosine, growth/differentiation factor 15, intercellular adhesion molecule, vascular cell adhesion molecule, tumor necrosis factor-α, vascular endothelial growth factor, interleukins -1ß, -6 and nitric oxide levels (NO, expressed as NOx) were determined. The remaining 27 individuals were used as a validation cohort. Ten patients with established resistant hypertension were enrolled from our Hypertension Clinic. RESULTS: There was a statistically significant difference in NOx levels between healthy controls and hypertensive patients/resistant hypertensive patients: 45.164 µmol/L ± 48.627 vs 17.763 µmol/L ± 10.333 (P=0.00004)/14.36 µmol/L ± 7.194 (P=0.00007). CONCLUSION: We identified a decrease in total NOx plasmatic levels in otherwise healthy patients with primary hypertension that was more profound in patients with resistant hypertension. Plasmatic levels of other determined endothelial substances did not differ among the groups. However, due to the significant variability of plasmatic NOx levels even in healthy controls and many factors that affect it, we cannot recommend it to be used to assess endothelial function routinely.

Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

Endothelial function, its relation to arterial hypertension and the possibility of its modulation.

Endothelium has both a protective and a very complex para-, endo- and autocrine functions. Vascular tone is determined as a balance between the production of vasodilating and vasoconstrictive substances. Among the most important vasodilators are nitric oxide (NO), PGI2, endothelial-derived hyperpolarizing factor (EDHF), adenosine and others, among the most important vasoconstrictors, endothelin-1 and angiotensin-2. Therapeutic goal of improving endothelial secretory function should be maximizing production of vasodilators and minimizing production of vasoconstrictors. Improvement of endothelial function can be achieved most effectively by following a healthy lifestyle (changing the diet to a Mediterranean type, sufficient physical activity, weight reduction and smoking cessation) and by initiating the treatment with ACE inhibitors and statins, when indicated. Large number of trials have shown that all of these interventions improve the prognosis of patients and a part of this effect may be mediated by improving endothelial dysfunction. Key words: endothelial dysfunction - endothelium - hypertension.

A multicentre study on unattended automated office blood pressure measurement in treated hypertensive patients.

AIMS: Unattended automated office blood pressure (uAutoOBP) may eliminate white-coat effect. In the present study, we studied its relationships to attended office blood pressure (BP) and ambulatory BP monitoring (ABPM). MATERIAL AND METHODS: Stable treated hypertensive subjects were examined in four Czech academic hypertension centres. uAutoOBP was measured with the BP Tru device; attended BP was measured six times: three times with auscultatory method (AuscOBP) by the physician followed optionally by three oscillometric measurements (OscOBP). ABPM was performed within one week from the clinical visit. RESULTS: Data on 172 subjects aged 63.7 ± 12.4 years with AuscOBP 127.6 ± 12.1/77.6 ± 10.0 mm Hg are reported. uAutoOBP was by 8.5 ± 9.0/3.0 ± 6.1 mm Hg lower than AuscOBP. The AuscOBP-uAutoOBP difference increased with the AuscOBP level and it did not depend on any other factor. OscOBP differed by 8.6 ± 8.6/1.9 ± 5.7 mm Hg from uAutoOBP. 24-hour mean BP was by 4.2 ± 12.1/3.5 ± 7.8 mm Hg lower than AuscOBP and by 4.3 ± 11.0/0.5 ± 6.9 mm Hg higher than uAutoOBP; the correlation coefficients of 24-hour mean BP with AuscOBP and with uAutoOBP did not differ (p for difference ≥.13). In the lowest BP group (systolic AuscOBP <120 mm Hg or diastolic AuscOBP <70 mm Hg), both AuscOBP and uAutoOBP were lower than 24-hour mean BP, while in the highest BP group (systolic AuscOBP ≥140 mm Hg or diastolic AuscOBP ≥90 mm Hg), they were higher. CONCLUSIONS: Compared to uAutoOBP, attended BP measurement gives higher values, both when measured with auscultatory or oscillometric method. Inter-individual variability of AutoOBP - uAuscOBP difference, as well of uAutoOBP - ABPM difference, is large. We did not prove that uAutoOBP would be associated to 24-hour ambulatory BP more closely than attended BP.

Worse prognosis of real-world patients with acute heart failure from the Czech AHEAD registry in comparison to patients from the RELAX-AHF trial.

AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial. METHODS AND RESULTS: A total of 5856 patients from the AHEAD registry (Czech registry of AHF) were divided into two groups according to RELAX-AHF criteria: relax-comparable (n = 1361) and relax-non-comparable (n = 4495). As compared with the relax-non-comparable group, patients in the relax-comparable group were older, had higher levels of systolic and diastolic blood pressure, lower creatinine clearance, and a higher number of comorbidities. Relax-comparable patients also had significantly lower short-term as well as long-term mortality rates in comparison to relax-non-comparable patients, but a significantly higher mortality rate in comparison to the placebo group of patients from the RELAX-AHF trial. Using AHEAD score, we have identified higher-risk patients from relax-comparable group who might potentially benefit from new therapeutic approaches in the future. CONCLUSIONS: Only about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin. AHF patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial.

[Clinical significance of natriuretic peptides in the differential diagnosis of dyspnea]. / Klinický význam natriuretických peptidu v diferenciální diagnostice dusnosti.

Acute dyspnea is one of the most common emergency department symptoms. But early diagnosis and treatment could be e challenging because of multiple potential causes. The gold standard biomarkers in cardiac dyspnea are B-type natriuretic peptide (BNP) and N-terminal pro-B-type (natriuretic peptide NT-pro BNP), which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. The purpose of this review is to analyze diagnostic potential of BNP and NT-pro BNP biomarkers use in patients with acute dyspnea. BNP and NT-proBNP are markers of cardiac stress but are not cardiac-specific. They have comparable clinical utility, and both help in excluding acute cardiac dyspnea but they cannot reliably discriminate systolic from diastolic HF.Key word: acute dyspnea - natriuretic peptide - heart failure.

Positive influence of being overweight/obese on long term survival in patients hospitalised due to acute heart failure.

BACKGROUND: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking. METHODS: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. RESULTS: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. CONCLUSION: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry.

AIMS: We analysed the contemporary incidence, outcomes, and predictors of heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) before discharge in patients with acute myocardial infarction (MI). The baseline presence of HF or LVSD, or its development during hospitalisation, increases short- and long-term risk after MI, yet its incidence, predictors, and outcomes have not been well described in a large, international, general MI population. METHODS AND RESULTS: The VALIANT registry included 5573 consecutive MI patients at 84 hospitals in nine countries from 1999 to 2001. A multivariable logistic survival model was constructed using baseline variables to determine the adjusted mortality risk for those with in-hospital HF and/or LVSD. Baseline variables were also tested for associations with in-hospital HF and/or LVSD. Of the 5566 patients analysed, 42% had HF and/or LVSD during hospitalisation. Their in-hospital mortality rate was 13.0% compared with 2.3% for those without HF and/or without LVSD. After adjustment for other baseline risk factors, in-hospital HF and/or LVSD carried a hazard ratio for in-hospital mortality of 4.12 (95% confidence interval: 3.08-5.56). Patients with HF and/or LVSD also had disproportionately higher rates of other cardiovascular events. CONCLUSIONS: HF and/or LVSD is common in the general contemporary MI population and precedes 80.3% of all in-hospital deaths after MI. Survivors of early MI-associated HF and/or LVSD have more complications, longer hospitalisations, and are more likely to die during hospitalisation. Although baseline variables can identify MI patients at highest risk for HF and/or LVSD, such patients are less likely to receive indicated procedures and medical therapies.