Early vascular damage in retinal microcirculation in arterial hypertension: the Czech post-MONICA study.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Wall-to-lumen ratio (WLR) may represent the earliest step in hypertension-mediated organ damage.Our objective was to compare functional and structural parameters of retinal microcirculation in a randomly selected urban population sample, in hypertensive and normotensive individuals. DESIGN AND METHOD: A total of 398 randomly selected individuals from an urban population aged 25-65 years, residing in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry, with data evaluable in 343 patients. Complete data were available for 342 individuals divided into four groups based on blood pressure and control status of hypertension: normotensive individuals ( n  = 213), treated controlled hypertensive individuals ( n  = 30), treated uncontrolled hypertensive individuals ( n  = 26), and newly detected/untreated hypertensive individuals ( n  = 73). RESULTS: There was a tendency to higher wall thickness in treated but uncontrolled hypertensive patients (compared to normotensive and treated controlled hypertensive individuals). WLR was significantly increased in treated but uncontrolled hypertensive patients as well as in individuals with newly detected thus untreated hypertension or in patients with known but untreated hypertension. There was no difference in WLR in treated, controlled hypertensive patients compared with normotensive individuals. CONCLUSION: Our results show that an increased WLR, reflecting early vascular damage, was found in newly detected individuals with hypertension and in untreated hypertensive patients, reflecting early hypertension-mediated vascular damage. Early initiation of hypertension treatment may be warranted.

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.

Longitudinal Trends in Severe Dyslipidemia in the Czech Population: The Czech MONICA and Czech Post-MONICA Study.

Background: Severe hypercholesterolemia is associated with an increase in the risk of developing atherosclerotic cardiovascular disease. The aim of this analysis was to assess longitudinal trends in severe dyslipidemia (defined as total cholesterol > 8 mmol/L or LDL-cholesterol > 5 mmol/L) in a representative population sample of the Czech Republic and to analyze the longitudinal trends in the basic characteristics of individuals with severe dyslipidemia. Methods: Seven independent cross-sectional surveys were organized in the Czech Republic to screen for major cardiovascular risk factors (from 1985 to 2015-2018). A total of 20,443 randomly selected individuals aged 25-64 years were examined. Results: The overall prevalence of severe dyslipidemia was 6.6%, with a significant downward trend from the fifth survey onwards (2000/2001). Over the study period of 30+ years, the individuals with severe dyslipidemia became older, increased in BMI, and did not change their smoking habits. Total cholesterol and non-HDL-cholesterol decreased significantly in both sexes throughout the duration of the study. Conclusions: Despite a significant improvement in lipids in the Czech Republic from 1985, substantially contributing to the decline in cardiovascular mortality, the number of individuals with severe dyslipidemia remained high, and in most cases, they were newly detected during our screening examinations and were thus untreated.

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.

Enhanced vitamin K expenditure as a major contributor to vitamin K deficiency in COVID-19.

OBJECTIVES: Vitamin K deficiency consistently associates with worse clinical outcome in COVID-19 patients. However, whether this is due to increased expenditure during inflammation or poor vitamin K status prior to infection remained unknown. METHODS: Dp-ucMGP levels of 128 individuals were measured for the post-MONICA study and were compared to SARS-CoV-2 PCR testing results. RESULTS: Dp-ucMGP levels prior to COVID-19 infection were not significantly different comparing PCR-negative, PCR-positive and not hospitalized, and PCR-positive and hospitalized patients. CONCLUSION: In this study, we demonstrate normal vitamin K status prior to infection in SARS-CoV-2 positive patients, supporting the theory of increased utilisation during disease.

Longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in the Czech population. Are there any sex differences?

Background: Hypertension is the most common cardiovascular disease which substantially increases cardiovascular morbidity and mortality. Despite the broad availability of antihypertensive medication, control of hypertension is not satisfactory worldwide. Objective: The study aim was to assess longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in a representative population sample of the Czechia from 1985 to 2016/2017, focusing on sex differences. Methods: A total of 7,606 men and 8,050 women aged 25-64 years were screened for major CV risk factors in seven independent cross-sectional surveys run consistently in the same six country districts of the Czechia between 1985 and 2016/2017. The population samples were randomly selected. Results: Over a study period of 31/32 years, there was a significant decline in systolic and diastolic blood pressure in both sexes, whereas the prevalence of hypertension decreased only in women. There was an increase in hypertension awareness in both sexes over the entire study period with consistently higher rates in women. The proportion of individuals treated with antihypertensive drugs increased significantly in both sexes throughout the study, again with consistently higher rates in women. Control of hypertension increased significantly over the study period with consistently higher rates in women. The age-adjusted trends in blood pressure, prevalence, awareness, and treatment of hypertension were significantly different in men and women, always in favor of women. The age-adjusted trends in control of hypertension in treated patients were equally poor in both sexes. Conclusion: There are significant differences in longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension between men and women, always in favor of women except for the control of hypertension in treated patients, where it is equally poor in both sexes.

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.

Blood pressure response to close or loose contact between physician and patient during attended office blood pressure measurement.

PURPOSE: Compared to unattended office blood pressure (uOBP), attended office blood pressure (aOBP) is higher. It is not known, however, to what extent distance between physician and patient influences blood pressure (BP) values. MATERIALS AND METHODS: Participants were stable hypertensive patients, followed in the university hospital-based out-patient center. During a session, automated office BP was measured three times after a pre-set five-minute pause, using the Omron 907 device; both aOBP and uOBP were done, in a random order. Simultaneously, beat-to-beat BP measurement was performed using the Finapress device. During aOBP, some participants were in close contact with the physician while others were in loose contact where the doctor was sitting in the room about 2.5 m apart. One year later, the second session with the same protocol was organized, but the close and loose contact were interchanged. The data were analyzed using a paired t-test. RESULTS: Complete data were collected in 32 patients, baseline uOBP was 122.8 ± 14.8/69.5 ± 11.7 mmHg. Systolic and diastolic aOBP with close contact was higher by 4.6 ± 6.9 and 1.9 ± 3.4 mmHg (p < 0.0007 and 0.0039, respectively), while aOBP with loose contact was not different from uOBP. Beat-to-beat BP increased during aOBP by 6.5 ± 8.5/3.3 ± 4.8 mmHg. The increase persisted during all the three aOBP measurements (p < 0.0001 for all systolic and diastolic BP values); the results were similar for close and loose contact. The peak increase during uOBP was of similar magnitude as during aOBP but it lasted shorter: it reached the significance level of p < 0.0001 only during the first uOBP measurement. CONCLUSIONS: Compared to uOBP, aOBP values were higher with close, but not with loose contact between physician and patient. These differences were, however, not detected by beat-to-beat BP measurement.

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.

The prognosis and therapeutic management of patients hospitalized for heart failure in 2010-2020.

AIMS: We analyzed the mortality risk and its predictors in patients hospitalized for heart failure (HF). METHODS: Patients discharged from hospitalization for acute decompensation of HF in 2010-2020 and younger than 86 years were followed (n=4097). We assessed the incidence and trends of all-cause death, its main predictors, and the pharmacotherapy recommended at discharge from the hospital. RESULTS: The 30 days all-cause mortality was in discharged patients 3.2%, while 1-year 20.4% and 5-years 55.4%. We observed a modest trend to decreased 1-year mortality risk over time. Any increase of year of hospitalization by one was associated with about 5% lower risk in the fully adjusted model. Regarding predictors of 1-year mortality risk, a positive association was found for age over 65, history of malignancy, and peak brain natriuretic peptide during hospitalization ≥10times higher than normal concentration. In contrast, as protective factors, we identified LDL ≥1.8 mmol/L, treatment with beta-blockers, renin-angiotensin axis blockers, statins, and implanted cardioverter in the same regression model. The ejection fraction category and primary etiology of HF (coronary artery disease vs. others) did not significantly affect the mortality risk in a fully adjusted model. CONCLUSIONS: Despite advances in cardiovascular disease management over the last two decades, the prognosis of patients hospitalized for heart failure remained highly unfavorable.

Low vitamin K status, high sclerostin and mortality risk of stable coronary heart disease patients.

Aim: We explored whether matrix Gla protein (MGP, natural calcification inhibitor) and sclerostin (glycoprotein responsible for osteoblast differentiation) interact in terms of mortality risk in coronary patients. Methods: 945 patients after myocardial infarction and/or coronary revascularization were followed in a prospective study. All-cause death, fatal or nonfatal cardiovascular events and heart failure hospitalizations were registered. Results: Either high desphospho-uncarboxylated MGP (dp-ucMGP) or high sclerostin were independently associated with 5-year all-cause/cardiovascular mortality. However, we observed an additional mortality risk in the coincidence of both factors. Concomitantly high dp-ucMGP (≥884 pmol/l) plus sclerostin (≥589 ng/l) were associated with increased all-cause mortality risk compared with 'normal' concentrations of both factors (HRR 3.71 [95% CI: 2.07-6.62, p < 0.0001]), or if only one biomarker has been increased. A similar pattern was observed for fatal, but not for nonfatal cardiovascular events. Conclusion: Concomitantly high MGP and sclerostin indicate increased mortality risk, which probably reflects their role in cardiovascular calcifications.

A novel nonsense mutation in the ß-subunit of the epithelial sodium channel causing Liddle syndrome.

PURPOSE: Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes coding of the epithelial sodium channel - SCNN1A, SCNN1B and SCNN1G. It is characterised by early onset of hypertension and variable biochemical features such as hypokalaemia and low plasma concentrations of renin and aldosterone. Phenotypic variability is large and, therefore, LS is probably underdiagnosed. Our objective was to examine a family suspected from Liddle syndrome including genetic testing and evaluate clinical and biochemical features of affected family members. MATERIALS AND METHODS: Thirteen probands from the Czech family, related by blood, underwent physical examination, laboratory tests, and genetic testing. Alleles of SCNN1B and SCNN1G genes were examined by PCR amplification and Sanger sequencing of amplicons. RESULTS: We identified a novel mutation in the ß-subunit of an epithelial sodium channel coded by the SCNN1B gene, causing the nonsense mutation in the protein sequence p.Tyr604*. This mutation was detected in 7 members of the family. The mutation carriers differed in the severity of hypertension and hypokalaemia which appeared only after diuretics in most of them; low aldosterone level (< 0.12 nmol/l) was, however, present in all. CONCLUSIONS: This finding expands the spectrum of known mutations causing Liddle syndrome. Hypoaldosteronemia was 100% sensitive sign in the mutation carriers. Low levels are observed especially in the Caucasian population reaching 96% sensitivity. Assessment of plasma aldosterone concentration is helpful for differential diagnosis of arterial hypertension. CONDENSED ABSTRACT: Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes encoding the epithelial sodium channel's α-, ß- and γ-subunit. It is usually manifested by early onset of hypertension accompanied by low potassium and aldosterone levels. We performed a physical examination, laboratory tests and genetic screening in 13 members of a Czech family. We found a new mutation of the SCNN1B gene which encodes the ß-subunit of the epithelial sodium channel. We describe the variability of each family member phenotype and point out the relevance of using aldosterone levels as a high sensitivity marker of Liddle syndrome in Caucasians.

Comparison of four routinely used vitamin D automated immunoassays.

BACKGROUND: To compare four automated immunoassays for the measurement of 25(OH)-vitamin D (25-OHD) and to assess the impact on the results obtained from a healthy population. METHODS: We analysed 100 serum samples on Unicel DxI 800 (Beckman Coulter), Architect i1000 (Abbott), Cobas e411 (Roche) and Liaison XL (DiaSorin). Passing-Bablok regression and Bland-Altman plots were used for method comparison. In order to categorise the obtained values, results were categorised into the following groups: 0-25 nmol/L, 25-50 nmol/L, 50-75 nmol/L and above 75 nmol/L and compared. The percentage of samples below 75 nmol/L, and below 50 nmol/L was then calculated for every method. RESULTS: According to paired comparisons, each method differs from others (p<0.0001) except Cobas vs Architect, which do not show a statistically significant difference (p=0.39). The strongest correlation was found between Liaison and Architect (ρ=0.94, p<0.0001). The percentage of samples below the recommended value of 75 nmol/L were: 70% (Architect), 92% (Liaison), 71% (Cobas) and 89% (Unicel). The percentage of samples below the value of 50 nmol/L were: 17% (Architect), 55% (Liaison), 28% (Cobas) and 47% (Unicel). CONCLUSIONS: The observed differences stem from the use of different analytical systems for 25-OHD concentration analysis and can result in different outcomes. The recommended values should be established for each assay in accordance with the data provided by the manufacturer or in the laboratory, in accordance with proper standardisation.

Uricemia in the acute phase of myocardial infarction and its relation to long-term mortality risk.

Aim: Although uric acid has antioxidant effects, hyperuricemia has been established as an indicator of increased cardiovascular mortality in various patient populations. Treatment of asymptomatic hyperuricemia in patients with acute myocardial infarction (MI) is not routinely recommended, and the efficacy of such treatment in terms of cardiovascular risk reduction remains doubtful. Materials & methods: In a prospective cohort study, we followed 5196 patients admitted for a MI between 2006 and 2018. We assessed the relationship between baseline uricemia and the incidence of all-cause death and cardiovascular mortality and the effect of long-term allopurinol treatment. Hyperuricemia was defined as serum uric acid >450 µmol/l in men and >360 µmol/l in women. Results: In the entire cohort, the 1-year all-cause and cardiovascular mortality rates were 8 and 7.4%, and the 5-year rates were 18.3 and 15.3%, respectively. Using a fully adjusted model, hyperuricemia was associated with a 70% increased risk of both all-cause death and cardiovascular mortality at 1 year, and the negative prognostic value of hyperuricemia persisted over the 5-year follow-up (for all-cause death, hazard risk ratio = 1.45 [95% CI: 1.23-1.70] and for cardiovascular mortality, hazard risk ratio = 1.52 [95% CI: 1.28-1.80], respectively). Treatment of asymptomatic hyperuricemia with allopurinol did not affect mortality rates. Conclusion: Hyperuricemia detected in patients during the acute phase of an MI appears to be independently associated with an increased risk of subsequent fatal cardiovascular events. However, hyperuricemia treatment with low-dose allopurinol did not prove beneficial for these patients.

The prognostic impact of renal function decline during hospitalization for myocardial infarction.

Aim: We analyzed the mortality risk of myocardial infarction (MI) patients according to renal function, observed during hospitalization. Materials & methods: Patients hospitalized for MI between 2006 and 2018 were followed (n = 5659). We divided the sample into four groups by estimated glomerular filtration (eGFR) [ml/min]: normal functions (lowest eGFR during hospitalization >60); transiently moderate insufficiency (lowest eGFR >30 and ≤60, highest >60); permanently moderate insufficiency (highest eGFR >30 and ≤60); severe insufficiency (highest and lowest eGFR ≤30). Results: Permanently moderate renal insufficiency indicates increased 5-years all-cause mortality (hazard risk ratio: 2.27 [95% CIs: 1.87-2.75], p < 0.0001), but a similar risk was found in patients with the only transient decline of renal functions (hazard risk ratio: 2.08 [95% CIs: 1.70-2.55], p < 0.0001). Both moderate insufficiency subgroups (transient/permanent) did not statistically differ regarding mortality risk. Conclusion: Even just fluctuation of eGFR toward moderate insufficiency during hospitalization represents an important prognostic indicator in MI patients.

Serum biomarkers, skin autofluorescence and other methods. Which parameter better illustrates the relationship between advanced glycation end products and arterial stiffness in the general population?

Stiffening of large arteries, clinically manifesting as increased aortic pulse wave velocity (PWV), is an inevitable outcome of aging. Among other mechanisms, impaired glucose metabolism plays an important role, leading to the deposition of advanced glycation end products (AGEs). This process is counterbalanced by the circulating soluble receptor for AGEs (sRAGE). We investigated the association between arterial stiffness on one side and multiple circulating biomarkers and the degree of skin deposition of AGEs on the other. In a cross-sectional design, 867 participants based on a general population sample (Czech post-MONICA studies) were examined. PWV was measured by SphygmoCor device (AtCor Medical Ltd.), while skin AGEs were measured using a dedicated autofluorescence method (AGE Reader mu®). To quantify the circulating status of AGEs, carboxymethyl lysine (CML) and sRAGE concentrations were assessed by ELISA, along with conventional glucose metabolism indicators. When analyzing the whole sample using multiple linear or logistic regression models and after adjustment for potential covariates, a significant association with PWV was found for fasting glycemia, HbA1c, sRAGE, skin AGEs, and the skin AGE-to-sRAGE ratio. Among these parameters, stepwise models identified the strongest association for the skin AGEs and AGE-to-sRAGE ratio, and this was also true when diabetic subjects were excluded. In contrast, neither CML nor its ratio relative to sRAGE showed any association with arterial stiffness. In conclusion, skin AGEs along with their ratio relative to sRAGE were closely associated with arterial stiffness and is a better indicator of the current status of deposited AGEs than other relevant factors.

The Prognostic Importance of Impaired Fasting Glycemia in Chronic Coronary Heart Disease Patients.

OBJECTIVES: Impaired glucose metabolism represents one the most important cardiovascular risk factors, with steeply raising prevalence in overall population. We aimed to compare mortality risk of impaired fasting glycaemia (IFG) and overt diabetes mellitus (DM) in patients with coronary heart disease (CHD). STUDY DESIGN: prospective cohort study METHODS: A total of 1685 patients, 6-24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. Overt DM was defined as fasting glucose ≥ 7 mmol/L and/or use of antidiabetic treatment, while IFG as fasting glucose 5.6-6.99 mmol/L, but no antidiabetic medication. The main outcomes were total and cardiovascular mortality during 5 years of follow-up. RESULTS: During follow-up of 1826 days, 172 patients (10.2%) deceased, and of them 122 (7.2%) from a cardiovascular cause. Both exposures, overt DM (n=623, 37.0% of the whole sample) and IFG (n=436, 25.9%) were associated with an independent increase of 5-year total mortality, compared to normoglycemic subjects [fully adjusted hazard risk ratio (HRR) 1.63 (95%CI: 1.01-2.61)]; p=0.043 and 2.25 (95%CI: 1.45-3.50); p<0.0001, respectively]. In contrast, comparing both glucose disorders one with each other, no significant differences were found for total mortality [HRR 0.82 (0.53-1.28); p=0.33]. Taking 5-years cardiovascular mortality as outcome, similar pattern was observed [HRR 1.96 (95%CI: 1.06-3.63) and 3.84 (95%CI: 2.19-6.73) for overt DM and IFG, respectively, with HRR 0.63 (95%CI: 0.37-1.07) for comparison of both disorders]. CONCLUSIONS: Impaired fasting glycaemia adversely increases mortality of CHD patients in the same extent as overt DM.

The role of advanced glycation end products in vascular aging: which parameter is the most suitable as a biomarker?

Advanced glycation end products (AGEs) are involved in several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of the vessel wall (arterial stiffness). Circulating soluble receptors for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding the natural course of arterial stiffening. In a prospective cohort study, we longitudinally followed 536 general population-based subjects (subsample of Czech post-MONICA study). Aortic pulse-wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE and carboxymethyl lysine (circulating AGEs) were assessed at the follow-up visit by ELISA, while skin AGEs were measured using the autofluorescence-based device AGE Reader. Using multiple regressions, we found significant association between ∆PWV/year as a dependent variable, and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest associations to ∆PWV/year were found for the ratio of these two factors (skin AGEs/sRAGE) [ß coeff = 0.0747 (SE 0.0189), p < 0.0001]. In a categorized manner, subjects with skin AGEs/sRAGE ratio ≥ 3.3 showed about twofold higher risk having ΔPWV/year ≥ 0.2 m/s [adjusted odds ratio was 2.09 (95% CI: 1.35-3.22), p = 0.001]. In contrast, neither circulating AGEs nor circulating AGEs/sRAGE showed any significant relation to ΔPWV/year. In conclusion, skin AGEs/sRAGE ratio seems to be a more sensitive biomarker of vascular aging than these single factors themselves or circulation status of AGEs.

Long-term trends in the incidence, treatment, hospital fatality and subsequent mortality from acute myocardial infarction in the Czech Republic.

AIMS: Studies on the incidence, acute and subsequent mortality from myocardial infarction are limited mostly to selected clinical cohorts and populations and cover relatively short periods. Our aim was to describe and analyse long-term trends on a national scale. METHODS: Acute myocardial infarction (AMI) was defined by the International Classification of Diseases (ICD)10; codes I21 and I22. Our natiowide 1994-2016 data on AMI mortality were obtained from the official mortality statistics (Czech Bureau of Statistics), data on morbidity (hospitalizations) from the National Register of Hospitalizations (Institute for Health Information and Statistics). For further analyses, data from the Czech EUROASPIRE I-V and Czech IMPACT studies were used. RESULTS: Over the 1994-2016 period the total number of AMI cases per year decreased from 34,084 to 19,015, that of patients hospitalized for AMI from 22,373 to 15,419, the total number of deaths due to AMI from 14,834 to 4,673, in those treated because of AMI from 3,794 to 1,137, and hospital fatality in patients treated for AMI decreased from 17% to 7.5%. Over the years 1997-2016, the one-year all-cause mortality rate after AMI declined from 25.1 to 17.9%, cardiovascular (CV) mortality from 22.3 to 14.2%, five-year all-cause mortality from 41.7 to 34%, and CV mortality from 34.1 to 23.6%. CONCLUSION: The Czech Republic has witnessed a pronounced decrease in AMI incidence and fatality and, consequently, long-term mortality. The decreasing incidence and improving course of AMI are due to progress in primary prevention, in acute coronary care and interventional cardiology, and in secondary coronary heart disease (CHD) prevention.

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.