The Prognostic Impact of Renal Function Decline during Hospitalization for Heart Failure.

INTRODUCTION: We aimed to evaluate the prognostic impact of renal insufficiency and fluctuation of glomerular filtration observed during hospitalization for heart failure (HF). METHODS: We followed 3,639 patients hospitalized for acute HF and assessed the mortality risk associated with moderate or severe renal insufficiency, either permanent or transient. RESULTS: After adjustment, severe renal failure defined as estimated glomerular filtration (eGFR) <30 mL/min indicates ≈60% increase in 5-year mortality risk. Similar risk also had patients with only transient decline of eGFR to this range. In contrast, we did not observe any apparent mortality risk attributable to mild/moderate renal insufficiency (eGFR 30-59.9 mL/min), regardless of whether it was transient or permanent. CONCLUSION: Even transient severe renal failure during hospitalization indicates poor long-term prognosis of patients with manifested HF. In contrast, only moderate renal insufficiency observed during hospitalization has no additive long-term mortality impact.

Does the Case Volume Experience of the Anesthesiologist Influence the Intraoperative Efficiency at All?

This editorial discusses the recent study conducted by Macias et al., revealing that anesthesiologists' case volume history has only a marginal impact on improving operating room efficiency, resulting in minimal clinical significance. The idea that a specific anesthesia team or type of anesthesia could enhance productivity has been previously investigated, yielding similar conclusions. Although the study primarily focuses on the time from patient arrival to the completion of anesthesia induction, excluding the latter part of anesthesia-controlled time, Macias et al. have made a valuable contribution by challenging the prevalent notion that less experienced anesthesiologists adversely affect operating room efficiency.

Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

The Current State and Usage of European Electronic Cross-border Health Services (eHDSI).

INTRODUCTION: European Union intends to enable cross-border health services through a program referred to as "MyHealth@EU". The first main service is the dispensation of medicine by interlinking national electronic prescription systems. The second one is the Patient Summary, which enables providing the basic set of patients' medical data. METHODS: The contemporary technical documentation of the project was studied and selected published Key Performance Indicators of the project were analyzed. Where necessary, data were acquired directly from the European Commission. RESULTS: Data from the start of the project (fourth quarter of 2019) until the second quarter of 2022 were analyzed. During this time both the overall number of EU countries with operational cross-border healthcare and their particular abilities in both services have risen. At present, there are eleven countries with capabilities in at least one of the services, of which nine have reported transactions. More countries are in the test phase now and will join the operational phase of the project shortly. DISCUSSION AND CONCLUSION: Nevertheless, the program is still used mostly for testing purposes. It seems that only electronic prescription and dispensation are commonly and widely used so far and only Estonian and Finnish patients usually get their medication dispensed abroad. The rest of the operational countries is still at present missing country pairs with a strong cross-border use case.

Dosing of basic pharmacotherapy and its effect on the prognosis of patients hospitalized for heart failure.

BACKGROUND: We analyzed the prescription and dosage of essential pharmacotherapy in chronic heart failure (HF) at the time of discharge from the hospitalization for cardiac decompensation and how it may have influenced the prognosis of the patients. METHODS: We followed 4097 patients [mean age 70.7, 60.2% males] hospitalized for HF between 2010 and 2020. The vital status we ascertained from the population registry, other circumstances from the hospital information system. RESULTS: The prescription of beta-blockers (BB) was 77.5% (or only 60.8% of BB with evidence in HF), 79% of renin-angiotensin system (RAS) blockers, and 45.3% of mineralocorticoid receptor antagonists (MRA). Almost 87% of patients were treated with furosemide at the time of discharge, while only ≈53% of patients with ischemic etiology of HF took a statin. The highest target dose of BB was recommended in ≈11% of patients, RAS blockers in ≈ 24%, and MRA in ≈ 12% of patients. In patients with concomitant renal insufficiency, the prescription of BB and MRA was generally less frequent and on a significantly lower dosage. In contrast, the opposite was true for the RAS blocker (however statistically insignificant). In patients with EF ≤ 40%, the prescription of BB and RAS blockers were more frequent but in a significantly lower dosage. On the contrary, MRAs were recommended in these patients more often and in higher doses. In terms of mortality risk, patients treated only with a reduced dose of RAS blockers showed a 77% higher risk of death within one year (or 42% within five years). A significant relationship was also found between mortality and the recommended dose of furosemide. CONCLUSIONS: The prescription and dosage of essential pharmacotherapy are far from optimal, and in the case of RAS blockers, this affected the patient's prognosis as well.

High leptin status indicates an increased risk of mortality and heart failure in stable coronary artery disease.

BACKGROUND AND AIMS: Leptin is an adipocyte-derived peptide involved in energy homeostasis and body weight regulation. The position of leptin in cardiovascular pathophysiology remains controversial. Some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as a neutral or even protective factor. We have explored whether high leptin affects the mortality and morbidity risk in patients with stable coronary heart disease. METHODS AND RESULTS: We followed 975 patients ≥6 months after myocardial infarction or coronary revascularization in a prospective study. All-cause or cardiovascular death, non-fatal cardiovascular events (recurrent myocardial infarction, stroke, or any revascularization), and hospitalizations for heart failure (HF) we used as outcomes. High serum leptin concentrations (≥18.9 ng/mL, i.e., 4th quartile) were associated with worse survival, as well as with a higher incidence of fatal vascular events or hospitalizations for HF. Even after full adjustment for potential covariates, high leptin remained to be associated with a significantly increased 5-years risk of all-cause death [Hazard risk ratio (HRR) 2.10 (95%CIs:1.29-3.42), p < 0.003], CV death [HRR 2.65 (95%CIs:1.48-4.74), p < 0.001], and HF hospitalization [HRR 1.95 (95% CIs:1.11-3.44), p < 0.020]. In contrast, the incidence risk of non-fatal CV events was only marginally and non-significantly influenced [HRR 1.27 (95%CIs:0.76-2.13), p = 0.359]. CONCLUSIONS: High leptin concentration entails an increased risk of mortality, apparently driven by fatal CV events and future worsening of HF, on top of conventional CV risk factors and the baseline status of left ventricular function.

Anaesthesia for non-cardiac surgical procedures in patients after heart transplantation.

Over the last 5 years, around 75 heart transplantations a year have been performed in the Czech Republic. According to these data and longer survival of these patients, it is obvious that non-cardiac surgical procedures in this particular group of patients are not rare. In the patients after heart transplantation, there is a significantly higher risk of undergoing elective and emergency surgical procedures due to various reasons. Appropriate anaesthesia and perioperative care are fundamentally affected by the knowledge of pathophysiological and pharmacological differences of transplanted heart. An equally important aspect is a lifetime immunosuppressive therapy in these patients.

The mortality risk of patients hospitalized for ischemic stroke between 2003 and 2019.

BACKGROUND: Stroke represents an essential part of the burden of cardiovascular diseases. Despite specific mortality from cerebrovascular diseases decreasing in the Czech Republic since the 80s, the trends in case fatality and individual risk of patients who suffered from stroke remain questionable. In patients hospitalized for ischemic stroke, we evaluated the mortality trends in the last two decades. METHODS: 9076 patients (mean age 71.8, 51.9% males) hospitalized for ischemic stroke between 2003 and 2019 were followed. The vital status we ascertained up to 31.12.2020, other circumstances from the hospital information system Results: In total, 5583 patients died during follow-up. The in-hospital fatality was 9.1%, 30-day mortality 14.2%, and 1-year mortality 28.4%. In patients hospitalized from 2003 to 2015, the 5-year mortality was 49.8%. No significant changes were noted for in-hospital fatality, 30-days, 1-year mortality, as well as 5-years mortality risk across more extensive periods (2003-07, 2008-11, 2012-15 and 2016-19). As expected, any decade of patient´s age was associated with about two-fold higher mortality risk. Intravenous thrombolysis, as part of initial management, markedly increased over time (from 2.4% in 2003-07 to 48.1% in 2016-19). However, this procedure affected beneficially only 1-year mortality risk, while regarding 5-years mortality was its effect neutral. CONCLUSIONS: Despite favorable trends in cerebrovascular events from a population perspective, the individual prognosis of patients who have suffered a stroke remains very poor.

Reference values of retinal microcirculation parameters derived from a population random sample.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found. Therefore, reference values for retinal microcirculation parameters have been established by age groups. Unattended automated office systolic BP, after adjusting for age, correlated significantly with wall-to-lumen ratio (WLR) and wall thickness (WT). Moreover, after adjusting for age and mean BP, a positive relationship has been found between carotid femoral pulse wave velocity and WT, WLR and wall cross-sectional area, indicating the interaction between micro- and macro-vasculature. In conclusion, our study is the first to provide reference values of retinal microcirculation parameters in a random Caucasian population sample. Our results have shown that, at the population level, the first structural changes in retinal microcirculation are those in lumen diameters. Of note, a close relationship between BP and vascular remodeling of retinal arterioles and between aortic stiffness and WLR of retinal arterioles suggests an interaction between micro- and macro-vasculature.

Medical Treatment in Coronary Patients: Is there Still a Gender Gap? Results from European Society of Cardiology EUROASPIRE V Registry.

PURPOSE: This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). METHODS: Analyses were based on the ESC EORP EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) survey. Consecutive patients between 18 and 80 years, hospitalized for a coronary event, were included in the study. Information on cardiovascular medication intake at hospital discharge and at follow-up (≥ 6 months to < 2 years after hospitalization) was collected. RESULTS: Data was available for 8261 patients (25.8% women). Overall, no gender differences were observed in the prescription and use of cardioprotective medication like aspirin, beta-blockers, and ACE-I/ARBs (P > 0.01) at discharge and follow-up respectively. However, a statistically significant difference was found in the use of statins at follow-up, in disfavor of women (82.8% vs. 77.7%; P < 0.001). In contrast, at follow-up, women were more likely to use diuretics (31.5% vs. 39.5%; P < 0.001) and calcium channel blockers (21.2% vs. 28.8%; P < 0.001), whereas men were more likely to use anticoagulants (8.8% vs. 7.0%; P < 0.001). Overall, no gender differences were found in total daily dose intake (P > 0.01). Furthermore, women were less likely than men to have received a CABG (20.4% vs. 13.2%; P < 0.001) or PCI (82.1% vs. 74.9%; P < 0.001) at follow-up. No gender differences were observed in prescribed (P = 0.10) and attended (P = 0.63) cardiac rehabilitation programs. CONCLUSION: The EUROASPIRE V results show only limited gender differences in the medical management of CHD patients. Current findings suggest growing awareness about risk in female CHD patients.

The coincidence of low vitamin K status and high expression of growth differentiation factor 15 may indicate increased mortality risk in stable coronary heart disease patients.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whether these two circulating biomarkers jointly influenced morbidity and mortality risk in patients with chronic coronary heart disease (CHD). METHODS AND RESULTS: 894 patients ≥6 months after myocardial infarction and/or coronary revascularization at baseline were followed in a prospective study. All-cause and cardiovascular mortality, non-fatal cardiovascular events (myocardial infarction, stroke, any revascularization), and hospitalization for heart failure (HF) were followed as outcomes. Desphospho-uncarboxylated MGP (dp-ucMGP) was used as a biomarker of vitamin K status. Both, increased concentrations of dp-ucMGP (≥884 pmol/L) and GDF-15 (≥1339 pg/mL) were identified as independent predictors of 5-year all-cause or cardiovascular mortality. However, their coincidence further increased mortality risk. The highest risk was observed in patients with high dp-ucMGP plus high GDF-15, not only when compared with those with "normal" concentrations of both biomarkers [HR 5.51 (95% CI 2.91-10.44), p < 0.0001 and 6.79 (95% CI 3.06-15.08), p < 0.0001 for all-cause and cardiovascular mortality, respectively], but even when compared with patients with only one factor increased. This pattern was less convincing with non-fatal cardiovascular events or hospitalization for HF. CONCLUSIONS: The individual coincidence of low vitamin K status (high dp-ucMGP) and high GDF-15 expression predicts poor survival of stable CHD patients.

Software used in emergency medical services.

Management of documentation in emergency medical services poses specific challenges due to its mode of operation. Electronic aids are already being used in this field. This article identifies four key systems: documentation management software, software for diagnostic devices, software for county emergency dispatches and navigational software. Each county emergency services provider in the Czech Republic is now equipped with all aforementioned systems. Most of these providers are also able to perform remote ECG consultations.

Role of inflammation and imunity in atherosclerosis and possible ways of their control.

Atherosclerosis and its clinical manifestations are characterised by ongoing arterial wall inflammation. Innate and adaptive imunity patterns are involved in all stages of atherosclerosis. Intensity of inflammation, more advanced proatherogenic imunity activity enhance development of cardiovascular (CV) disease. Efforts to control inflammation and imune proatherogenic patterns face considerable problems, but recent clinical studies offer promissing results. Statins have antiinflammatory effect, but PCSK9 monoclonal antibodies not. SGLT2 inhibitors (gliflozins) have a proven antiinflammatory effect and this might partly explain their protective CV effect. Recent clinical studies, COLCOT with colchicine and CANTOS with cinakinumab decreased inflammatory activity, CV mortality and incidence of defined CV endpoints. Other approaches to control inflammation in atherosclerosis are considered, namely blocation of proatherogenic cytokins by specific antibodies and intervention of metabolism of inflammatory cells. Vaccination against PCSK9 is being developed. Further studies may aim on active IL-1beta - IL-6 axis blocation nad on blocation of proatherogenic cytosins. Patients with signs of persistent inflammation, with specified inflammatory stage and with atherosclerotic leasion more precisely defined will be included.

Is There Really an Association of High Circulating Adiponectin Concentration and Mortality or Morbidity Risk in Stable Coronary Artery Disease?

Adiponectin has several beneficial properties, namely, on the level of glucose metabolism, but paradoxically, its high concentrations were associated with increased mortality. We aimed to clarify the impact of high serum adiponectin on mortality and morbidity in patients with stable coronary artery heart disease (CAD). A total of 973 patients after myocardial infarction and/or coronary revascularization were followed in a prospective cohort study. All-cause and cardiovascular (CV) death, non-fatal cardiovascular events, and hospitalizations for heart failure (HF) were registered as outcomes. High serum adiponectin levels (≥8.58 ng/ml, i. e., above median) were independently associated with increased risk of 5-year all-cause, CV mortality or HF [with HRR 1.57 (95% CI: 1.07-2.30), 1.74 (95% CI: 1.08-2.81) or 1.94 (95% CI: 1.20-3.12), respectively] when adjusted just for conventional risk factors. However, its significance disappeared if brain natriuretic peptide (BNP) was included in a regression model. In line with this, we observed strong collinearity of adiponectin and BNP. Additionally, major adverse cardiovascular event (i. e., CV death, non-fatal myocardial infarction or stroke, coronary revascularization) incidence risk was not associated with high adiponectin. In conclusion, the observed inverse association between adiponectin concentrations and mortality risk seems to be attributable to concomitantly increased BNP, rather than high adiponectin being a causal factor.

Longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease in hypertensive and normotensive adults.

The purpose: To evaluate longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease (CKD) in Czech adults with and without arterial hypertension (HT).Materials and methods: Two independent cross-sectional surveys were performed in 2006-2009 and 2015-2018, each screening involving 1% population random sample of the general population of nine districts of the Czech Republic aged 25-64 years, stratified by age and gender. Hyperuricaemia was defined as serum uric acid ≥ 420 µmol/l in men, and ≥ 360 µmol/l in women. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 and/or albumin/creatinine ratio ≥ 3 mg/mmol.Results: Final analyses included 3504 individuals examined in 2006-2009, and 2309 in 2015-2018. The overall prevalence of hyperuricaemia increased from 16.4% to 25.2% in men (p < 0.001), and from 7.6% to 10.9% in women (p < 0.001), whereas the overall prevalence of CKD declined from 6.8% to 3.6% in men (p = 0.001), and from 7.6% to 4.8% in women (p < 0.001). There was no interaction between HT and hyperuricaemia in either gender; the increase in hyperuricaemia prevalence was observed both in hypertensive and normotensive adults and was accompanied by the increased prevalence of abdominal obesity. Contrarily, there was an interaction between HT and CKD in both men (p < 0.001) and women (p = 0.011); the CKD prevalence declined only in hypertensive individuals, specifically in those using antihypertensive medication and was accompanied by the increased use of renin-angiotensin-aldosterone system (RAS) inhibitors and calcium channel blockers (CCBs).Conclusions: Over the period of 10 years, the overall prevalence of hyperuricaemia increased, while the prevalence of CKD decreased. An increase in the prevalence of hyperuricaemia was observed both in hypertensive and normotensive individuals and was accompanied by an increase in the prevalence of abdominal obesity. A decline in the prevalence of CKD was only observed in hypertensive individuals and was accompanied by the increased use of RAS inhibitors and CCBs.

Primary aldosteronism in a general population sample. The Czech post-MONICA study.

Purpose: Primary aldosteronism (PA) is considered the most common form of secondary hypertension, however, its prevalence, particularly in a general population, is still a matter of debate. The aim of our study was to evaluate the prevalence of PA in a randomly selected general population sample.Materials and methods: A total of 1940 individuals (1% population random sample) aged 25-64 years were screened for major cardiovascular risk factors in six districts of the Czech Republic. Hypertension was defined as a mean of two blood pressure readings ≥140/90 mmHg at one visit or taking antihypertensive medication. Within this population, 740 individuals were labelled as hypertensives and 650 of them sampled for the analysis of direct plasma renin and serum aldosterone. The diagnosis of PA was based on elevated serum aldosterone, low plasma renin and high aldosterone/renin (ARR) ratio and was also verified by a confirmatory test with saline infusion.Results: Positive ARR was found in 52 (8%) individuals (64% women, 36% men, however, due to substatntial proportion of reluctatnt participants to undergo a further work-up (27%), we could confirm the diagnosis of PA only in 13 of them (2%). Aldosterone-producing adenoma was found in one case only, seven patients had idiopathic type and five individuals refused potential surgical treatment therefore, adrenal venous sampling was not performed.Conclusion: Elevated serum aldosterone together with low renin and high ARR were found in 52 (8%) of hypertensives selected from a general population sample, however, the diagnosis of PA was confirmed only in 13 of them (2%). This study based on a general population survey highlighted the difficulty of conducting epidemiological studies on primary aldosteronism in a relatively healthy cohort part of whom did not provide the level of collaboration that is necessary to assess the true prevalence of this condition.

Anesthesia Information Management Systems in the Czech Republic from the Perspective of Early Adopters.

Although theoretical studies on Anesthesia Information Management Systems (AIMS) have proved their benefits, much less attention has been paid to researching the actual adoption of AIMS. Only a few studies from the USA and Western Europe have been published up to now. The purpose of this article is to assess the adoption, motivation for, and barriers to, usage of AIMS from the perspective of early Czech adopters of these systems. A questionnaire was used to gather adopters' views on motivating factors, benefits encountered after introduction and obstacles perceived to adopting AIMS. Data about usage, costs and functionalities of each of the AIMS was obtained using semi-structured telephone interviews prior to sending out the questionnaire. Five AIMS from three different vendors in four academic hospitals (20% of Czech hospitals of this type) were identified. Improved clinical documentation and convenience for anesthesiologists was reported from every site. Lack of funds, however, was identified as the primary barrier to further adoption. The cost of introduction of AIMS per operating room varied between 1000 and 40,000 US dollars. Although the number of AIMS in the Czech Republic is limited, findings suggest that benefits have been experienced on every site. Findings corroborate previous studies from the USA and Western Europe.

Adherence to cardiovascular prevention principles in subjects at high risk.

BACKGROUND: Asymptomatic high-risk individuals represent one of the highest priorities of cardiovascular prevention, in clinical practice frequently overlooked. We analyzed the real adherence to recommended principles of cardiovascular prevention in primary care subjects. METHODS: Our analysis is based on random general population sample, examined in the frame of post-MONICA survey in 2016/17. Each subject was categorized with regard to its individual cardiovascular risk (based on Sixth Joint European Guidelines) and the real adherence to recommended targets was ascertained. RESULTS: In total 898 subjects aged 25-75 years (47% males) were analyzed. Of them, 16.7% were classified into “very high risk“ and 36.8% into “high risk“ subgroup; remaining 46.5% were only at moderate or low risk. Regarding adherence to recommended principles, in “very high risk“ category only 58.7% abstain from any form of tobacco, 38% reported appropriate physical activity (150 minutes of at least moderate activity weekly), 16.7% had recommended body constitution (BMI 20-25 kg/m2 ), 39.3% appropriate blood pressure (.

Incidence of cardiovascular events in patients with stabilized coronary heart disease: the EUROASPIRE IV follow-up study.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.

ß-N-Acetylhexosaminidases-the wizards of glycosylation.

ß-N-Acetylhexosaminidases (EC 3.2.1.52) are a unique family of glycoside hydrolases with dual substrate specificity and a particular reaction mechanism. Though hydrolytic enzymes per se, their good stability, easy recombinant production, absolute stereoselectivity, and a broad substrate specificity predestine these enzymes for challenging applications in carbohydrate synthesis. This mini-review aims to demonstrate the catalytic potential of ß-N-acetylhexosaminidases in a range of unusual reactions, processing of unnatural substrates, formation of unexpected products, and demanding reaction designs. The use of unconventional media can considerably alter the progress of transglycosylation reactions. By means of site-directed mutagenesis, novel catalytic machineries can be constructed. Glycosylation of difficult substrates such as sugar nucleotides was accomplished, and the range of afforded glycosidic bonds comprises unique non-reducing sugars. Specific functional groups may be tolerated in the substrate molecule, which makes ß-N-acetylhexosaminidases invaluable allies in difficult synthetic problems.