Long-term trajectory of renal dysfunction and related risk factors in patients with apparently treatment-resistant and non-resistant arterial hypertension.

Objectives: Evidence suggests that renal function increasingly deteriorates in patients with apparently treatment-resistant hypertension (ATRH) in comparison with those who have non-resistant arterial hypertension (NAH). We aimed to assess the long-term decline in renal function between these patient groups and identify specific risk factors contributing to the progression of renal dysfunction. Methods: Data for 265 patients with ATRH and NAH in a hypertension excellence centre were retrospectively evaluated. Demographic characteristics, co-morbidities, laboratory findings, secondary causes of hypertension, medication and exposure to contrast agents were assessed. To address differences between groups, adjustment with linear mixed-effect models was used. Results: Data from the first 4 years of follow-up were evaluated. After adjustment for age and diabetes, which were identified as independent risk factors for renal dysfunction progression in the study cohort, the mean decrease in estimated glomerular filtration rate per year was steeper with ATRH than with NAH (-1.49 vs. -0.65 mL/min/1.73 m2 per year; difference in slope, 0.83 mL/min/1.73 m2 per year; 95% confidence interval [CI]: 0.25-1.41, p = 0.005). In subgroup analyses, without Holm-Bonferroni correction, the prescription of MRA indicated a faster decline in renal function in ATRH. Following correction, no specific therapeutic risk factor was associated with faster progression of renal dysfunction. Conclusions: Renal function declines twice as fast with ATRH compared with NAH, independently of age and diabetes. Larger studies are needed to reveal risk factors for renal dysfunction in patients with hypertension.

High blood pressure (arterial hypertension) is a significant risk factor for kidney function decline. Resistant hypertension represents a subtype of hypertension that is difficult to treat and requires multiple antihypertensive agents to achieve effective blood pressure control. Recent research suggests that individuals with resistant hypertension are at greater risk of kidney dysfunction.This study analyses data from adult patients with arterial hypertension and resistant hypertension followed-up for a mean duration of 6.4 years.A faster decline in kidney function was observed in patients with resistant hypertension. This suggests that renal function in these patients should be closely monitored.After statistical evaluation, no medication was found to be associated with an increased risk of kidney failure progression. However, two specific medications, spironolactone and eplerenone, raised suspicion and require further exploration in larger prospective studies.

News in cardiology.

The article summarizes new advances in cardiology published in 2022, which have an impact to everyday practice of not only internists and cardiologists. The administration of polypill to patients after myocardial infarction (SECURE study), early pharmacotherapy of hypertension in pregnant women with blood pressure exceeding 140/90 mmHg (CHAP study), or the administration of dapagliflozin to patients with heart failure with preserved or mildly reduced ejection fraction (DELIVER study) have been shown to be effective. Patients with heart failure do not have to limit their sodium intake (SODIUM-HF study), on the contrary, they benefit from up-titration of guideline-recommended drugs to the maximum tolerated doses as quickly as possible (STRONG-HF study). For antihypertensives, it does not matter whether they are taken in the morning or in the evening (TIME study), nor has there been found any difference in the incidence of cardiovascular events with hydrochlorothiazide and chlortalidone (DCP study). In patients with increased cardiovascular risk, highly sensitive troponin should be measured before non-cardiac surgery as well as 24 and 48 hours after surgery to detect perioperative myocardial infarction. Different blood pressure and oxygenation targets in patients after resuscitation for out-of-hospital cardiac arrest do not affect the outcomes of their treatment.

What is new in 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing non­cardiac surgery.

In 2022, the European Society of Cardiology has published updated guidelines for the cardiovascular evaluation and management of patients undergoing non-cardiac surgery. In this article we briefly summarize the most important recommendations with an emphasis on their use in everyday clinical practice - from the complex assessment of cardiovascular risk and prediction of cardiovascular complications, through the indication of basic paraclinical examinations, the importance of biomarkers, adjustments to pharmacotherapy of heart failure, adjustments to anticoagulant and antiplatelet therapy, to other specifics of individual cardiovascular and other diseases and their importance in the perioperative period. Knowledge and use of these recommendations have the potential to improve the prognosis of patients undergoing various types of surgical procedures.

Whats new in 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST segment elevation?

The article sumarizes the 2020 ESC Guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation. The diagnostics of ACS consists in assessment of chest pain, EKG and cardiac troponin. Troponin should be evaluated by high sensitivity assay. 0h/1h algorithms should be used to rule-in or rule-out ACS. Patients with a positive troponin have higher risk of cardivascular events and mortality and the early invasive treatment should be applied in these patients. In the guidelines several antithrombotic stretegies for different clinical conditions are mentioned, where the cornerstone for the length and intensity of antithrombotic treatment is the evaluation of bleeding risk. Further on the revascularization aspects and strategies are debated in the guidelines. Finally there are mentioned two specific conditions of ACS - Myocardioal infarction with non-obstructive coronary arteries and Spontaneous coronary artery dissection.

Whats new in 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice?

2021 ESC Guidelines on cardiovascular disease prevention in clinical practice provides a comprehensive view on preventive cardiology. It presents strategies to reduce the burden of atherosclerotic cardiovascular disease (CVD), both at the individual level and at the population level. Healthy lifestyle and aggressive control of cardiovascular risk factors remain the cornerstone of prevention. Classification of individuals into risk groups based on their clinical characteristics followed by a stepwise treatment-intensification is a novel recommended approach. Updated risk charts - SCORE2 and SCORE2-OP - are intended for estimation of 10-year fatal and non-fatal CVD risk in apparently healthy individuals. Targets and goals for LDL cholesterol, blood pressure, and glycaemic control remain as recommended in recent ESC Guidelines.

Acute infections in kidney transplant recipients.

Immunosuppressed kidney transplant recipients have a high risk of infectious complications. A variety of infections of viral, bacterial, or mycotic etiology, including opportunistic infections, occur in this group of patients, but bacterial infections are primarily responsible for the high infection-related mortality. Of the bacterial infections, urinary tract infections and pneumonia are the most common, often requiring hospitalization and temporary reduction of immunosuppressive therapy after consultation of the transplant center. In addition to symptoms due to the location of the infection, fever is often present. The differential diagnosis of fever and/or high inflammatory activity is specific to patients after kidney transplantation. In addition to infectious causes, we consider drug-related fever, a rejection episode, a relapse of systemic disease or in patients with graft failure in dialysis treatment graft intolerance syndrome (“symptomatic graft”). Saving the patients life, which often requires a significant reduction in immunosuppressive therapy, always takes precedence over preventing a rejection episode. Infection prevention is an integral part of the care of transplant patients, including the recommendation of vaccination where possible.

Use of telemedicine in patients with heart failure.

Chronic heart failure (HF), like any chronic disease, is a medical and socioeconomic burden. The number of patients with HF is increasing and our effort is to apply the most effective way of care in practice, preferably together with using telemedicine. Early diagnosis, therapy establishment and reduction of rehospitalizations play the key role in HF management. For patients for whom we add telemedicine (telephone consultation, physiological data transfer, data transfer from implantable devices, teleconsultation) and especially if we are able to provide the background of a well-functioning telemedicine center that is able to respond promptly to the data, we can recognize and respond to the deterioration in health status in a timely manner. Telemedicine has benefit in all aspects of care mentioned above, but mostly in the reduction of re-hospitalizations, which is related to the reduction of morbidity and mortality. Telemedicine in HF is also cost-effective.

Comprehensive approach to a patient with arterial hypertension and dyslipidemia.

Arterial hypertension together with dyslipidemia, diabetes and smoking are the most severe risk factors for cardiovascular (CV) disease. The Czech Republic is among the countries with a high risk of cardiovascular disease. To reduce cardiovascular mortality and morbidity in our patients, a comprehensive approach to treatment and, in most cases, aggressive control of all risk factors is needed. This article summarizes current diagnostic and therapeutic procedures for arterial hypertension and dyslipidaemia, as well as the concept of vascular age, which can help us to communicate CV risk with patients.

CROP: correlation-based reduction of feature multiplicities in untargeted metabolomic data.

SUMMARY: Untargeted liquid chromatography-high-resolution mass spectrometry analysis produces a large number of features which correspond to the potential compounds in the sample that is analyzed. During the data processing, it is necessary to merge features associated with one compound to prevent multiplicities in the data and possible misidentification. The processing tools that are currently employed use complex algorithms to detect abundances, such as adducts or isotopes. However, most of them are not able to deal with unpredictable adducts and in-source fragments. We introduce a simple open-source R-script CROP based on Pearson pairwise correlations and retention time together with a graphical representation of the correlation network to remove these redundant features. AVAILABILITY AND IMPLEMENTATION: The CROP R-script is available online at www.github.com/rendju/CROP under GNU GPL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Arterial Hypertension and Risk of Recurrent Event in Young Ischemic Stroke Patients.

INTRODUCTION: In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients. METHODS: The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification. RESULTS: Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510-24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000). CONCLUSION: AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.

Hypertension healthcare professional beliefs and behaviour regarding patient medication adherence: a survey conducted among European Society of Hypertension Centres of Excellence.

PURPOSE: Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence. MATERIALS AND METHODS: Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres. RESULTS: Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring. CONCLUSIONS: The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits.

SGLT2 inhibitors - a new pillar for the treatment of heart failure.

DAPA-HF and EMPEROR-REDUCED clinical trials have shown significant benefits of dapagliflozin and empagliflozin in the treatment of heart failure with reduced ejection fraction regardless of the presence or absence of diabetes mellitus. Their results support the implementation of SGLT2 inhibitors into clinical practice in patients with heart failure, due to their efficacy, safety, and minimal side effects. Their mechanism of action does not depend on the state of neurohumoral activation and SGLT2 inhibitors have a simple dosing regimen, without the need for dose titration. In addition to cardioprotective properties, SGLT2 inhibitors also have a very significant nephroprotective effect. Empagliflozin and dapagliflozin have recently been approved by regulatory authorities for the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction and are becoming one of the basic pillars of treatment for these patients.

Blood vessel ageing and vascular memory.

As blood vessels age, their structure and function gradually change. This process is influenced by diet and the presence of modifiable risk factors. Blood vessel status can be clinically evaluated by measuring arterial stiffness or ankle-brachial index. The patients vascular age can be calculated using the SCORE project and indicates what age would have a person with the same calculated cardiovascular risk, whose risk factors were all within the normal range. The vascular age can be positively influenced by nonpharmacological measures, hypolipidemic statin therapy and also by hypertension pharmacotherapy, especially renin-angiotensin-aldosterone system inhibitors. Long-term follow-up of patients enrolled in clinical trials with antihypertensive and hypolipidemic agents suggests the existence of so-called vascular memory, since the beneficial effects of these interventions on reduction of cardiovascular morbidity and mortality persist for many years after completion of these studies. Early initiation of preventive measures has a greater effect.

Plasma levels and leucocyte RNA expression of adipokines in young patients with coronary artery disease, in metabolic syndrome and healthy controls.

OBJECTIVES: Little is known about the role of adipokines in the pathogenesis of coronary artery disease in young patients. The aims of this study were to compare serum levels of adipokines and expression of adipokines in peripheral blood leukocytes in patients with premature coronary artery disease (CAD), metabolic syndrome and healthy individuals. DESIGN AND METHODS: Sixty-five patients with premature CAD (men 18-45years old and women 18-55years old) formed the study group. The control groups were 75 patients with metabolic syndrome and 50 healthy individuals. For each group, RNA expression in peripheral blood leukocytes was determined for 24 different adipokines and 11 adipokines were examined in serum. RESULTS: In individuals with CAD, serum visfatin levels were significantly higher than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7µg/L, P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3µg/L, P<0.001) and ZAG2 (45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating curve (ROC) analysis for testing the validity of these adipokines in the diagnosis of CAD compared to control groups provided the following areas under the curve (AUC): omentin-1 AUC 0.97 (cut-off ≤222µg/L), ZAG2 AUC 0.89 (cut-off ≤51.7mg/L) and visfatin AUC 0.74 (cut-off ≥1.0µg/L) (P<0.001 in all cases). Visfatin and omentin-1 serum levels did not differ between the acute phase of myocardial infarction and the chronic phase of CAD. In patients with CAD, we found no significant relation between mRNA expression and adipokine concentration. CONCLUSION: Serum omentin-1, visfatin and ZAG2 could serve as biomarkers of premature CAD in young apparently healthy people.

Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra.

Specific diagnostic markers are the key to effective diagnosis and treatment of inborn errors of metabolism (IEM). Untargeted metabolomics allows for the identification of potential novel diagnostic biomarkers. Current separation techniques coupled to high-resolution mass spectrometry provide a powerful tool for structural elucidation of unknown compounds in complex biological matrices. This is a proof-of-concept study testing this methodology to determine the molecular structure of as yet uncharacterized m/z signals that were significantly increased in plasma samples from patients with phenylketonuria and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. A hybrid linear ion trap-orbitrap high resolution mass spectrometer, capable of multistage fragmentation, was used to acquire accurate masses and product ion spectra of the uncharacterized m/z signals. In order to determine the molecular structures, spectral databases were searched and fragmentation prediction software was used. This approach enabled structural elucidation of novel compounds potentially useful as biomarkers in diagnostics and follow-up of IEM patients. Two new conjugates, glutamyl-glutamyl-phenylalanine and phenylalanine-hexose, were identified in plasma of phenylketonuria patients. These novel markers showed high inter-patient variation and did not correlate to phenylalanine levels, illustrating their potential added value for follow-up. As novel biomarkers for 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, three positional isomers of 3-methylglutaconyl carnitine could be detected in patient plasma. Our results highlight the applicability of current accurate mass multistage fragmentation techniques for structural elucidation of unknown metabolites in human biofluids, offering an unprecedented opportunity to gain further biochemical insights in known inborn errors of metabolism by enabling high confidence identification of novel biomarkers.

Multianalyte Determination of NOACs Using LC-MS/MS and Comparison with Functional Coagulation Assays.

BACKGROUND: Detection of new oral anticoagulant (NOAC) levels by screening, special and global tests, and liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) is important in clinical situations when the cause of bleeding needs to be determined. METHODS: We compared a routine coagulation test, special function test for NOACs, global coagulation test, and an LC-MS/MS method that enables simultaneous determination of apixaban, dabigatran and rivaroxaban in human plasma within one analysis to determine the optimal indication of the comparison methods, including their limitations and interferences. RESULTS: This study was conducted on a set of blood samples from 116 patients treated with NOACs. The results of both specific dilute thrombin time (dTT) tests for dabigatran provided the same results as the activated partial thromboplastin time (aPTT) screening test in comparison with LC-MS/MS as a reference. The dTT assay HemosIL® showed better results for low concentrations when compared to LC-MS/MS than dTT HYPHEN® as HemosIL® uses a non-linear calibration curve. Results of the specific anti-Xa assay yielded better results than the prothrombin time test in comparison with LC-MS/MS as a reference, especially for apixaban, but also for rivaroxaban. Our LC MS/MS method is simply feasible, but only in a specialized laboratory. The method is easy-to-use for the simultaneous determination of all dabigatran, apixaban and rivaroxaban by LC-MS/MS within three minutes with a concentration range of 1 to 500 µg/L without dilution. CONCLUSIONS: In the normal practice of the coagulation laboratory, it is advisable to use specific tests for NOAC determination as screening and global assays are not sufficiently specific. The dTT test is the optimal choice for dabigatran determination and for xabans to determine anti-Xa activity. The LC-MS/MS method is suitable as an arbitration method for serious conditions.

Ambulatory screening for obstructive sleep apnea in patients with resistant arterial hypertension.

OBJECTIVE: Obstructive sleep apnea (OSA) is one of the most common causes of secondary arterial hypertension. It is important to rule out OSA as a cause of resistant hypertension. The ApneaLink device is a simple and cost-efficient outpatient examination, but its usefulness in screening OSA in resistant hypertension has not yet been evaluated. METHODS: A total of 69 patients with resistant arterial hypertension were enrolled. Patients underwent a physical examination, including the use of ApneaLink, followed by respiratory polygraphy. The presence of OSA was assessed by the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), mean nocturnal desaturation (SpO2), and percentage of sleep time with SpO2 less than 90%. RESULTS: There was no significant difference between the values of AHI found during the use of ApneaLink and respiratory polygraphy (mean 30.4 ± 21.7 vs. 37.2 ± 20.9, P = 0.07). ApneaLink had 77.3% sensitivity and 100% specificity to diagnose OSA with the area under the ROC curve 0.866 (P < 0.001). We also found no significant difference in mean SpO2 (91.3 ± 2.5 vs. 90.9 ± 3.3%, P = 0.22). The ODI evaluated via ApneaLink was significantly lower than by the polygraphy (31.1 ± 18.3 vs. 43.9 ± 24.8, P < 0.001), while the measured percentage of sleep time with SpO2 less than 90% was higher (31.8 ± 23.7 vs. 23.3 ± 24.4, P = 0.001). The severity of OSA was correctly determined by ApneaLink in 50.7% of patients, underestimated in 23.2% and overestimated in 26.1%. CONCLUSIONS: The use of ApneaLink is a suitable method for screening the presence of OSA in patients with resistant hypertension, but to accurately assess the severity of OSA, respiratory polygraphy or polysomnography is required.

[Dyslipidemia and hypertension - what to worry about more?] / Dyslipidemie a hypertenze - ceho se obávat více?

Dyslipidemia is present in every other patient with arterial hypertension. With increasing blood pressure and cholesterol levels, the risk of cardiovascular events increases proportionally. Treatment of dyslipidemia appears to lower cardiovascular mortality to a greater extent than treatment of hypertension. A significant proportion of patients with dyslipidemia indicated for drug therapy are not treated at all or treated insufficiently and do not reach the target values. Concurrent treatment of hypertension and dyslipidemia reduces the incidence of cardiovascular events significantly more than treating only one of these diseases. An even better efficacy of combined treatment of hypertension and dyslipidemia can be achieved by improving patient adherence using fixed drug combinations.Key words: arterial hypertension - cardiovascular events - dyslipidemia - fixed combinations -treatment.

Heart rate is a useful marker of adherence to beta-blocker treatment in hypertension.

OBJECTIVES: Suboptimal medication adherence is common among patients with hypertension. Measurements of plasma or urinary levels of antihypertensive drugs are useful, but not widely available. The aim of our study was to investigate the relation of patients' heart rates to their serum beta-blocker levels. METHODS: We correlated 220 measurements of serum beta-blocker levels in 106 patients with apparently resistant hypertension to their corresponding office heart rate. A significant proportion, 44.6% of patients, were non-adherent to beta-blocker treatment according to serum level measurement. Non-adherent patients had significantly higher heart rates (80.9 vs. 66.6 bpm, p < .001), systolic (157.4 vs. 147.0 mm Hg, p = .002) and diastolic blood pressure (91.1 vs. 87.2 mm Hg, p = .041) in comparison to adherent patients. RESULTS: Heart rate above 75.5 beats per minute predicted non-adherence to beta-blocker treatment with a sensitivity of 62.5%, specificity 86.8% and AUC ROC 0.802 (p < .001). Higher heart rate cutoff might be applicable for nebivolol but was not determined due to the low number of patients treated with nebivolol. CONCLUSIONS: We concluded that heart rate was shown to be a good predictor of non-adherence to beta-blocker treatment, and might become a quick and easy measure to determine patient adherence in hypertensive patients.

Fast and sensitive analysis of beta blockers by ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry.

This paper presents a method for the determination of acebutolol, betaxolol, bisoprolol, metoprolol, nebivolol and sotalol in human serum by liquid-liquid extraction and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. After liquid-liquid extraction, beta blockers were separated on a reverse-phase analytical column (Acclaim RS 120; 100 × 2.1 mm, 2.2 µm). The total run time was 6 min for each sample. Linearity, limit of detection, limit of quantification, matrix effects, specificity, precision, accuracy, recovery and sample stability were evaluated. The method was successfully applied to the therapeutic drug monitoring of 108 patients with hypertension. This method was also used for determination of beta blockers in 33 intoxicated patients.