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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 GDF15 expression predicts poor survival of stable CHD patients. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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.

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.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].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.

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.

Východisko: Asymptomaticke osoby se zvýseným kardiovaskularnim rizikem představuji jednu z priorit kardiovaskularni prevence, v praxi ale casto opomijenou. Nasim cilem bylo objektivizovat, jak vysokorizikove osoby dosahuji lecebných cilů v primarni peci. Metoda: Analýza zahrnovala nahodný vzorek obecne populace, vysetřený v ramci populacniho průzkumu postMONICA v letech 2016-2017. Probandi byli kategorizovani podle sveho individualniho kardiovaskularniho rizika na zakladě principů 6. spolecných evropských doporuceni a porovnana byla jejich skutecna kontrola rizikoveho profilu s teoretickými doporucenými cili kardiovaskularni prevence. Výsledky: Celkem bylo do analýzy zařazeno 898 subjektů ve věku 25-75 let (47 % mužů). Mezi nimi, 16,7 % subjektů bylo klasifikovano do kategorie "velmi vysoke riziko", 36,8 % jako "vysoke riziko", zatimco zbylých 46,5 % jako jen mirně zvýsene nebo nizke celkove individualni riziko. Z hlediska adherence k doporuceným principům, ve skupině s "velmi vysokým rizikem" abstinovalo od tabaku v jakekoliv podobě jen 58,7 %, naležitou fyzickou aktivitu (≥ 150 min alespoň mirne aktivity týdně) nahlasilo 38 %, doporucenou tělesnou konstituci (BMI 20-25 kg/m2) vykazovalo 16,7 %, naležitý krevni tlak (< 140/90 mm Hg) 39,3 % a cilove hodnoty LDL-cholesterolu (< 1,8 mmol/l) dosahlo jen 8,7 % subjektů. V kategorii "vysokeho rizika" byla adherence k těmto cilům nasledujici: 83,9 % (abstinence od tabaku), 32,7 % (fyzicka aktivita), 17 % (tělesna konstituce), 58,2 % (krevni tlak) a 30,8 % (LDL-cholesterol < 2,5 mmol/l). Přijatelnějsi byla v obou rizikových kategoriich kontrola glukozoveho metabolismu (HbA1c < 53 mmol/mol u diabetiků), tj. 75 % a 81 %, respektive. Zavěr: Celkova adherence k doporuceným principům kardiovaskularni prevence vysokorizikových osob je v primarni peci velmi daleko od sveho optima a markantni je toto zejmena u subjektů s velmi vysokým rizikem

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) [β coeff = 0.0747 (SE 0.0189), p

Aim: We aimed to establish the association between sclerostin (a glycoprotein involved in bone metabolism) and development of pulse wave velocity (PWV) in the general population. Methods: A prospective cohort study with a total of 522 subjects. Aortic PWV was measured twice (at baseline and after approximately 8 years of follow-up) and intraindividual change in PWV per year (ΔPWV/year) was calculated. Results: ΔPWV/year increased across the sclerostin quintiles, but generally in a strong age-dependent manner. However, a significant independent positive association between sclerostin and ΔPWV/year was observed exclusively in C allele carriers of rs5186 polymorphism for the angiotensin II receptor 1 (n = 246). Conclusion: Sclerostin concentrations were associated with an accelerated natural course of arterial stiffening, but only in interaction with renin-angiotension system.

Introduction: Leptin is an adipocyte-derived peptide, involved in energy homeostasis and regulation of body weight. The position of leptin in cardiovascular pathophysiology remained controversial, some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as protective. Hypothesis: We explore whether high leptin status affects the mortality/ morbidity risk in stable patients with coronary heart disease. Methods: 975 patients, ≥6 months after myocardial infarction (EUROASPIRE cohort) were followed in a prospective study. All-cause or CV death, non-fatal events (myocardial infarction, stroke or any revascularization) and hospitalizations for heart failure (HF) were registered as outcomes Results: High serum leptin concentrations (≥18.9 ng/mL, i.e. 4 th quartile) indicate inferior survival, as well as a higher incidence of fatal vascular event or hospitalizations for HF ( see Figure). Even after full adjustment for potential covariates, high leptin was associated with significantly increased 5-years risk of all-cause death [HRR 2.10 (95%CIs:1.29-3.42), p 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.

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’ concentration s of both factors (HRR 3.71 [95% CI: 2.07–6.62, p

Uvod: Sekundarni kardiovaskularni (KV) prevence po prodělanem infarktu myokardu (IM) je nemeně důležita než lecba akutniho IM. Lepsi KV prevence může rozhodujici měrou přispět k pokracovani pozitivnich trendů KV morbidity a mortality v Ceske republice v poslednich třech desetiletich. Cil: Stanovit, jak jsou do praxe implementovana nedavna evropska doporuceni pro sekundarni prevenci ischemicke choroby srdecni (ICHS) (2012). Metodika: Konsekutivně a retrospektivně bylo vybrano 624 pacientů, mužů a žen ve věku ≤ 80 let, hospitalizovaných pro akutni koronarni syndrom a/nebo chirurgickou ci katetrizacni koronarni revaskularizaci. Byl proveden rozbor chorobopisů a nasledně byli ambulantně vysetřeni respondenti, minimalně sest měsiců, maximalně dva roky po přijeti k hospitalizaci. Výsledky: Celkem bylo vysetřeno 406 respondentů. Z nich 20 % byli aktivni kuřaci, 44,8 % bylo obeznich (BMI ≥ 30), v pasmu nadvahy a obezity (BMI ≥ 25) bylo 85,5 % respondentů, centralně obeznich (obvod pasu ≥ 102 cm u mužů, ≥ 88 cm u žen) 70,2 %, doporucovane fyzicke aktivity (30 minut 5× týdně) nedosahlo 85 %. Krevni tlak zvýsený nad hodnoty požadovane v doporucenich kardiovaskularni prevence z roku 2012 (≥ 140/90 mm Hg, u diabetiků ≥ 140/80 mm Hg) mělo 55,1 % pacientů, zvýsený LDL-cholesterol (≥ 1,8 mmol/l) 63,5 % pacientů. Diabetes (znamý a nově diagnostikovaný) vykazovalo 41,2 % respondentů, prediabetes 23,4 %. Při použiti glukozoveho tolerancniho testu to bylo 44,7 %, respektive 32,3 %. V době naseho vysetřeni bylo 88,4 % pacientů leceno antiagregancii, 81,3 % beta-blokatorem, 78,8 % inhibitory angiotenzin konvertujiciho enzymu (ACEI) nebo antagonistou receptoru ATII, 92,1 % statinem, 92,9 % prodělalo koronarni revaskularizaci. Zavěr: Větsina pacientů v sekundarni prevenci ICHS ma nezdravý životni styl - nezdravou dietu a nedostatecnou pohybovou aktivitu. Prevalence nadvahy, obezity a diabetu je velmi vysoka, prevalence obezity a centralni obezity se dale zvýsila. Farmakoterapie je v sekundarni prevenci použivana u větsiny pacientů, ale doporucených hodnot krevniho tlaku, lipidoveho a glycidoveho metabolismu je dosahovano jen u mensiny.

Řada intervencnich studii prokazala, že pacienti s ischemickou chorobou srdecni (ICHS) maji užitek z agresivnějsiho sniženi LDL cholesterolu. Cilem teto analýzy bylo posoudit, nakolik se v průběhu poslednich deseti let změnila adherence k doporucene cilove hodnotě LDL cholesterolu a davkovaci zvyklosti u statinu v sekundarni prevenci ICHS obecně. Analyzovano bylo celkem 1 349 pacientů (21,7 % žen) o průměrnem věku 64,9 roku (směrodatna odchylka [SD] ± 9,0) po akutnim koronarnim syndromu a/nebo koronarni revaskularizaci, vysetřených ve třech nezavislých kohortach (ceska data z projektu EUROASPIRE III, IV a V). Globalni kontrola hypercholesterolemie se sice v průběhu sledovaneho obdobi výrazně zlepsila, avsak stale až 52 % pacientů v roce 2017 nedosahovalo doporucene cilove hodnoty LDL (< 1,8 ,mmol/l). Stejně tak preskripce statinu v nejvyssi davce (atorvastatin 80 mg ci ekvivalent) sice signifikantně vzrostla, stale vsak cinila pouze 23 % v kohortě z roku 2017. Na zakladě individualnich hodnot LDL jsme se dale pokusili odhadnout potencial eventualni intenzifikace hypolipidemicke lecby. Maximalni možna up-titrace statinu by vedla k vzestupu adherence k doporucene hodnotě o dalsich 12 %, zatimco po přidani ezetimibu by hodnoty LDL < 1,8 mmol/l mohlo teoreticky dosahovat až 73 % pacientů. ně, jakkoliv naprosta větsina pacientů s ICHS uživa statin, adherence k doporucene cilove hodnotě LDL zůstava hrubě nedostatecna. Maximalni up-titrace statinu a zejmena castějsi uživani kombinacni hypolipidemicke lecby by mohlo situaci zlepsit.

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.

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 Conclusions Impaired fasting glycaemia adversely increases mortality of CHD patients in the same extent as overt DM.

Aims: Several papers reported that unattended automated office blood pressure (uAutoOBP) is closely related to daytime ambulatory blood pressure monitoring (ABPM). In the present study, we aim to study uAutoOBP and its relation to 24-hour ABPM and ABPM variability. Material and methods: Stable treated hypertensive subjects were examined in two Czech academic hypertension centres. uAutoOBP was measured with the BP Tru device; attended BP three times with auscultatory method (AuscOBP) by the physician. ABPM was performed within one week from the clinical visit. Results: Data on 98 subjects aged 67.7 ± 9.3 years with 24-hour ABPM 120.3 ± 10.6/72.7 ± 7.9 mm Hg are reported. uAutoOBP was lower than 24-hour (by −5.2 ± 11.3/−0.5 ± 6.9 mm Hg) and daytime (by −6.7 ± 12.82.4 ± 8.0 mm Hg) ABPM and the individual variability of the difference was very large (up to 30 mm Hg). The correlation coefficients between ABPM and uAutoOBP were similar compared to AuscOBP (p ≥ .17). Variability of uAutoOBP, but not AuscOBP, readings during one clinical visit was related to short-term blood pressure variability of ABPM. The difference between AuscOBP and uAutoOBP was larger in patients with white-coat effect compared to other blood pressure control groups (25.1 ± 7.0 vs. 2.2 ± 10.3 mm Hg; p = .0036). Conclusions: Our study shows that uAutoOBP is not good predictor of ambulatory blood pressure monitoring, not even of the daytime values. It might, however, indicate short-term blood pressure variability and, when compared with AuscOBP, also detect patients with white-coat effect.

Aim: We analyzed to what extent measurement protocol influenced individual blood pressure (BP) and achievement of treatment target in patients with coronary heart disease. Methods: In a subsample of Czech EUROASPIRE III–V survey participants (n = 913), we compared the per-protocol BP measurement (by automated oscillometric device OMRON at the beginning of survey procedure) with control auscultatory measurement (by physician during interview). Results: Per-protocol approach produced significantly (p Conclusion: Per-protocol oscillometric technique was not equivalent to conventional auscultatory measurement and seriously over-rated the real nonachievement of BP target in observational surveys.

Background: It was suggested that depression and anxiety might be associated with increased cardiovascular risk in both primary and secondary prevention. In stable coronary heart disease (CHD) pati...

Circulating levels of soluble receptor for advanced glycation end-products (sRAGE) have been suggested to have a protective role in neutralizing advanced glycation end-products (AGEs) and their pathological effects on vessel walls. We aimed to investigate the association between the circulating concentration of sRAGE and the dynamics of arterial wall stiffening as a manifestation of vascular aging in the general population. In a prospective cohort study, we longitudinally followed 530 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 were assessed at baseline by ELISA (R&D Systems). The average ∆PWV/year significantly decreased across the sRAGE quintiles (p = 0.048), and a drop by one sRAGE quintile was associated with an ~21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥ 0.2 m/s). Subjects in the bottom quintile of sRAGE (

Background: In stable coronary heart disease (CHD) patients we aimed to assess the predictive potential of only mild increase of brain natriuretic peptide (BNP) in subjects free from symptoms or diagnostic criteria of heart failure (HF).Methods: We examined 967 patients, at least 6 months after myocardial infarction or coronary revascularization and divided them into three categories: 'overt HF' (NYHA II-IV, objective signs of HF, chronic treatment with furosemide and/or spironolactone or history of hospitalisation for HF), 'subclinical HF (BNP over 150 ng/mL, but no criterion of overt HF)' and 'no HF' (no above mentioned criterion present). Follow-up was done to assess 5-years all-cause mortality.Results: Overt and subclinical HF (by definition) had 38.8% and 9.6% of patients, respectively. In analyses adjusted for classical risk factors and other possible covariates, both overt and subclinical HF were independently associated with increased mortality compared to no HF subjects [hazard risk ratio 1.99 (95%CI:1.02-3.91) and 3.01 (95%CI:1.90-4.78), respectively. The risk of total mortality was similar in overt and subclinical HF patients [HRR 1.30 (95%CI: 0.72-2.36)]. Within overt HF group, those with BNP >150 ng/mL had also higher mortality risk than those with low BNP levels [HRR 2.79 (95%CI: 1.67-4.68)]. The addition of left ventricle ejection fraction into definition of HF groups did not affect main results.Conclusions: Mild increase of BNP in generally stable and asymptomatic CHD patients identifies high individual mortality risk in the same extend that presence of clinically manifest HF.

Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification, while growth differentiation factor 15 (GDF-15) regulatory cytokine of inflammation or angiogenesis. We explore whether the coincidence of both factors affects the mortality/morbidity risk in stable coronary patients. 979

Background: Soluble receptors for advanced glycation end-products (sRAGEs) have been suggested to have a protective role neutralizing the advanced glycation end-products (AGEs) and their pathological effect on vessel walls. We aimed to investigate the association between circulating concentrations of sRAGEs and dynamic of arterial wall stiffening as a manifestation of vascular ageing in general population. Methods: In a prospective cohort study, we longitudinally followed 530 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 intra-individual change of PWV per year (ΔPWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA methods (R& Systems). Results: Average ΔPWV/year significantly increased across the sRAGE quintiles (p = 0.0008) and drop by one sRAGE quintile was associated with ≈21% increase in the relative risk of accelerated age-dependent stiffening (ΔPWV/year ≥0.2 m/sec). In a categorized manner, subjects in the bottom quintile of sRAGE (

Background: Advanced glycation end products (AGEs) are involved into several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of vessel wall (arterial stiffness). Circulating soluble receptor for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor [1,2]. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding natural course of arterial stiffening. Methods: 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 (ΔPWV/year) was calculated. Concentrations of sRAGE and carboxylmethyl lysine (circulating AGEs) were assessed at follow-up visit by ELISA, while skin AGEs were measured using autofluorescence-based device AGE Reader. Results: Using multiple regressions, we found significant association between ΔPWV/year as dependent variable and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest association to ΔPWV/year were found for ratio of these two factors (skin AGEs/sRAGE) [coeff = 0.0747 (SE 0.0189), p < 0.0001]. In categorized manner, subjects with skin AGEs/sRAGE ratio ≥3.3 showed about two-fold higher risk having PWV/year ≥0.2 m/sec [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 PWV/ year. Conclusions: Skin AGEs/sRAGE ratio seems to be more sensitive biomarker of vascular ageing than these single factors themselves or circulation status of AGEs [3].

Background: Accumulation of advanced glycation end-products (AGEs) is one of pathophysiological processes, responsible for progressive stiffening of vessel wall. In contrast, soluble isoform of receptor for AGEs (sRAGE) act as “decoy” and physiological defense against circulating AGEs. We hypothesized that low levels of sRAGE might be associated with accelerated age-dependent arterial stiffening. Methods: We followed 429 population-based subjects (mean age 50.8 (±11.7) years, 41.5% males) in prospective study. Aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples by ELISA methods (R&D Systems). Baseline examination was done in 2008/9, while follow-up visit in 2016/17 (median time of follow-up was 7.6 years) Results: Mean intra-individual increase of aPWV during follow-up was 1.37 (±1.88) m/sec and was inversely associated with baseline sRAGE concentration – the aPWVV difference [follow-up minus baseline] across its quintiles was 2.08((±1.89), 1.51(±2.16), 1.20(±2.10), 0.99(±1.70), 1.13(±1.21) in 1st–5th quintiles of sRAGE, resp.; p = 0.003 (adjusted for age, gender and baseline mean arterial pressure) Baseline concentration of sRAGE

Background We aimed to clarify the impact of metabolic syndrome (MetS) as assessed by different definitions on the cardiovascular mortality in patients with coronary heart disease (CHD). Methods A total of 1692 patients, 6–24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. MetS was identified using four different definitions: standard National Cholesterol Education Program definition (NCEP-ATPIII) based on the presence of ≥ 3 of the following factors: increased waist circumference, raised blood pressure, hypetriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glycemia; modified NCEP-ATPIII definition (similar, but omitting antihypertensive treatment as an alternative criterion); presence of “atherogenic dyslipidemia”; or “hypertriglyceridemic waist”. The primary outcome was a fatal cardiovascular event at 5 years. Results During 5-year follow-up, 117 patients (6.9%) died from a cardiovascular cause. Patients with MetS by modified NCEP-ATPIII (n = 1066, 63.0% of the whole sample) had significantly higher 5-year cardiovascular mortality [adjusted hazard risk ratio (HRR) 2.01 [95%CI:1.26–3.22]; p = 0.003] than subjects without MetS. However, when testing single MetS component factors, the majority of attributable mortality risk was driven by increased fasting glycemia (≥ 5.6 mmol/L) [HRR 2.69 (95%CI:1.29–5.62), p = 0.009] and the significance of MetS disappeared. None of the other MetS definitions, i.e., standard NCEP-ATPIII (n = 1210; 71.5%), “hypertriglyceridemic waist” (n = 455; 26.9%) or “atherogenic dyslipidemia” (n = 223; 13.2%) were associated with any significant mortality risk. Conclusions The co-incidence of MetS has a limited mortality impact in CHD patients, while an increase in fasting glycemia seems to be more a specific marker of mortality risk.