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Predavanje predstavlja osvrt na dosadašnje spoznaje u liječenju hipertoničara sa srčanim zatajenjem, posebno u skupini sa očuvanom ejekcijskom frakcijom a posebno u skupini sa reduciranom ejekcijskom frakcijom.

Activation of endothelial TGF-β signaling may be an important driver of atherogenesis and plays a key role in induction of vessel wall inflammation and development and progression of atherosclerosis. Previously, our studies on consumption of n-3 polyunsaturated fatty acids (n- 3 PUFAs) enriched eggs have shown a beneficial effect, by changing the free fatty acid profile to a more favorable lower n6/n3 ratio, lowering total cholesterol and LDL-cholesterol levels in cardiovascular patients with no adverse effects of daily eggs' consumption. The aim of this study was to determine effect of eggs enriched with n-3 PUFAs, vitamin E, selenium and lutein on the serum levels of pro-inflammatory cytokines. Randomized, double-blind, controlled, interventional study (Clinical Trials ID: NCT04564690) was conducted in patients with chronic coronary syndrome (diagnosed according to ESC guidelines for the diagnosis and management of chronic coronary syndromes, 2019) who consumed 3 hen eggs per day for 3 weeks. Control patients consumed ordinary: n3-PUFAs (438 mg/day), lutein (110 mg/day), selenium (0.181 mg/day) and vitamin E (595 mg mg/day) hen eggs and Nutri4 group patients consumed enriched hen eggs: n3-PUFAs (1026 mg/day), lutein (616 mg/day), selenium (0.191 mg/day) and vitamin E (1098 mg mg/day). All patients used statins and other standard drug therapy for CAD (ACE inhibitors, beta blockers, antiplatelet drugs), and some of them used ezetimibe depending on lipid profile. Written informed consent was obtained from each subject. The study protocol and procedures conformed with the standards set by the latest revision of the Declaration of Helsinki and were approved by the Ethical Committee of Osijek University Hospital. Serum levels of TGF-β, C3a, IFN-gamma, IL-6, IL-10, IL-17A(CTLA-8), IL-23, MCP-1 (CCL2) and TNF-alpha were measured with ThermoFisher Scientific ProcartaPlex antibody- based magnetic bead reagent kits and panels for multiplex protein quantitation using the Luminex 200 instrument platform. Quantitation was performed using ProcartaPlex Analysis Application and expressed as concentration in pg/ml, (sample N=9-10 per group). For group comparisons a OneWayANOVA test was used. Within-group comparisons were performed using paired t-test or Wilcoxon test, statistical significance was set as P

Consumption of n-3 polyunsaturated fatty acids (n- 3 PUFAs) pharmacological substitutes has strong potential to reduce cardiovascular risk and prevent adverse outcomes in existing cardiovascular diseases. The natural way of taking n-3 PUFAs is through food enriched with these nutrients - functional food. The aim of part of the research conducted at the Scientific Center of Excellence for Personalized Health Care is to produce hen eggs enriched with n-3 PUFAs and to examine the effect of consumption of such eggs on microvascular function in young, healthy subjects and patients with acute and chronic coronary heart disease. All protocols were approved by the relevant ethics committees and participants gave written informed consent. The results of these studies, which were conducted in protocols with 2 or 3 enriched or plain eggs a day for 3 weeks, showed that there was a significant benefit and enhancement of microvascular reactivity after eating enriched eggs in young healthy subjects and athletes, while no such effect was observed in cardiovascular patients. The effect was more pronounced at daily doses of n-3 PUFAs > 770mg / day. At the same time, no adverse effect of egg consumption on microvascular function, blood pressure, lipid profile or markers of inflammation and oxidative stress was observed in any group of subjects. On the contrary, some of the markers were improved in both healthy subjects and cardiovascular patients. In conclusion, consumption of n-3 PUFAs enriched eggs has a positive effect on vascular health. In principle, eggs should be a regular part of the daily diet.

Introduction and Aim: This project tested the hypothesis that suppression of renin-angiotensin system (RAS) and sympathetic activity by 7 day high-salt (HS) diet lead to endothelial and leukocyte activation and further, impaired microvascular reactivity in humans, by increasing oxidative stress. Materials and Methods: Project lasted for 54 months (April 2017-October 2021). Overall 132 young healthy individuals were included in project studies. All subjects adhered to a 7-day low-salt diet (3.5g salt/day), followed by a 7-day HS diet (~14.7g salt/day) protocol. Functional assessment of microvascular endothelial function, adrenergic system activity, body composition and fluid status, RAS activity, catecholamines concentration, biomarkers of oxidative status, pro- and anti-inflammatory cytokines, frequencies of peripheral blood lymphocytes, and biomarkers of endothelial activation were measured before and after HS diet. To specifically test the role of oxidative stress and sympathetic system activity in changes of microvascular reactivity due to the HS diet one group of subjects was supplemented with oral antioxidants during the HS diet, while the other group was subjected to a mental stress test. Results and Conclusions: 7-day HS diet suppresses RAS and impairs microvascular endothelium- dependent vasodilation in healthy individuals ; these changes are independent of blood pressure, body composition or fluid retention, but are the consequences of the unique effect of HS on endothelial function. HS diet induces oxidative disbalance, with antioxidant supplementation during HS diet preserving both oxidative status and endothelial microvascular reactivity. HS diet also suppresses sympathetic activity which represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in healthy individuals. HS diet induces lymphocyte activation, resulting in enhanced production of pro-inflammatory, but also anti-inflammatory cytokines, while increased oxidative stress, due to HS loading, alters immune regulatory mechanisms. Taken together, oxidative disbalance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals.

Introduction:Even though regular physical activity is known to reduce oxidative stress level, strenuous exercise and overtraining increases oxidative stress level in competitive athletes. Thus, proper nutrition which maintains proper oxidative balance is very important in athlete’s performance and attaining high level achievements. Analyses of dietary habits in various athletes’ groups found that a substantial proportion of the studied populations did not reach the dietary goals for many 725726macro-and micronutrients, including those with antioxidant properties. Thus, this study aimed to investigate the effect of antioxidant nutrient supplementation in a form of functional food on measurable biomarkers of oxidative stress and antioxidant capacity in competitive athletes.Methods:Thirty- one young healthy competitive athletes (all men) were instructed toeat three hard boiled hen eggs per day during study protocol that lasted for 21 days (total of 63 eggs). Subjects were divided in experimental NUTRI4 group (14 subjects) which consumed n-3 polyunsaturated fatty acids (n-3 PUFAs), selenium, vitamin E and lutein enriched hen eggs (1050 mg of n-3 PUFA/day, 0.06 mg of selenium/day, 3.29 mg of vitamin E/day, and 1.85 mg of lutein/per day), and in control group (17 subjects) which consumed regular hen eggs produced on the same farm (249 mg of n-3 PUFA per day, 0.05 mg of selenium/day, 1.79 mg of vitamin E/day, and 0.33 mg of lutein/per day). Serum protein concentration of 8- iso prostaglandin F2α (8-iso-PGF2α) and hydrogen peroxide and peroxynitrite (DCF-DA) formation in peripheral blood mononuclear cells (PBMCs) were measured as a markers of oxidative stress level, while serum enzyme activity of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured as markers of enzymatic antioxidant defense, before and after respective diet protocol.Results8-iso-PGF2α serum protein concentration significantly decreased in the NUTRI4 group, while the control group remained unchanged following the respective diet protocol. Similarly, formation of hydrogen peroxide and peroxynitrite (DCF-DA) in PBMCs significantly decreased in the NUTRI4 group, and remained unchanged in controls. Serum activity of CAT, GPX and SOD did not significantly change after the diet protocol neither in control nor Nutri4 group.Conclusion:Three-week antioxidants supplementation in a form of functional food (n-3 PUFAs, selenium, vitamin E and lutein enriched hen eggs) significantly reduced oxidative stress level in competitive athletes potentially by modifying non-enzymatic (or other enzymatic, beside measured) endogenous antioxidant pathways.

Objective: Present study aimed to determine the effect of consumption n-3 PUFAs, selenium, lutein, and vitamin E enriched hen eggs on endothelium-dependent and endothelium-independent vasodilatation of forearm skin microcirculation in athletes. Design and methods: Thirty-one competitive athletes participated in study, divided in Control group (N=14) who ate 3 regular hens’ eggs/daily, and Nutri4 group (N=17) who ate 3 n-3 PUFAs, selenium, lutein, and vitamin E enriched hen eggs/daily for 3 weeks. Blood pressure, serum lipids and serum concentration of functional nutrients were measured at the beginning and at the end of respective dietary protocol. Endothelium-dependent (post-occlusive reactive hyperemia, PORH ; and iontophoresis of acetylcholine, AChID) and endothelium-independent responses (iontophoresis of sodium nitroprusside, SNPID) of skin microvascular blood flow was assessed using Laser Doppler flowmetry (LDW) before and after dietary protocol. Results: Both PORH and AChID were significantly enhanced after consumption of enriched hen eggs compared to baseline measurement and compared to Control group post-dietary protocol. PORH and AChID were not altered in Control group post-dietary protocol compared to baseline in control group. SNP-induced dilation (SNPID) was not affected by dietary protocols. MAP (mean arterial pressure) was lower after 3-week protocol at NUTRI4 group, while lipid profile was unaltered by diet and similar between Control and NUTRI4 groups. Functional nutrients were higher in serum after diet in NUTRI4 group compared to Control group and pre-diet values. Conclusion: This study demonstrated enhanced microvascular reactivity in response to consumption of functionally enriched eggs.

Introduction: Matrix metalloproteinase 9 (MMP- 9) actively participates in remodeling of blood vessels in both physiological and pathological processes associated with increased oxidative stress. This study aimed to determine whether 7-days HS diet is accompanied by changes in serum levels of MMP-9 and to test whether MMP-9 is associated with microvascular reactivity in healthy population. Methods: 20 young healthy individuals (10 men and 10 women, 18-24 years) were subjected to 7- days low-salt (LS) diet (∼3.5 g of salt/day ; ) followed by 7-days high-salt (HS) diet (∼14 g of salt/day). Compliance to diet was assessed from 24h-urinary sodium excretion. Serum MMP-9 concentration was measured by commercially available ELISA kit before and after HS. Forearm skin microvascular blood flow in response to vascular occlusion (PORH) and iontophoresis of acetylcholine (AChID) was assessed by laser Doppler flowmetry before (LS) and after HS diet. Results: Changes in calculated daily salt intake from 24h sodium excretion confirmed that participants conformed to the diet protocols. Serum MMP-9 concentration was not significantly changed following HS diet compared to LS (MMP-9 ng/ml LS 691.6±162.7 vs. HS 711.2±117.4, P>0.05). PORH and AChID were significantly reduced following HS compared to LS (PORH LS 134±35 vs. HS 114±29, P

Carnosine is a dipeptide synthesized in the body from β-alanine and L-histidine. It is found in high concentrations in the muscle, brain, and gastrointestinal tissues of humans and is present in all vertebrates. Carnosine is a non-enzymatic free-radical scavenger and a natural antioxidant and has anti-inflammatory and neuroprotective properties. Carnosine reduces lipid peroxidation of fatty acid in cell membranes during oxidative stress, and also inhibits oxidative modification of protein exposed to hydroxyl radicals. One of its mechanisms to protect organisms from oxidative stress is the chelation of transition metals ; furthermore, it may improve antioxidant activity of different antioxidative enzymes. Carnosine is widely used among athletes in the form of supplements, but rarely in the population of cardiovascular or diabetic patients. Its component, the amino acid beta-alanine, is particularly interesting as a dietary supplement for athletes because it increases muscle carnosine, and improves effectiveness of exercise and stimulation and contraction in muscles. Studies in diabetic mice suggest that increased IL-6 and TNF-α were significantly suppressed by intake of histidine or carnosine. Since excessive generation of IL-6 and TNF-α compromise insulin sensitivity, suppression of IL-6 and TNF-α by carnosine and histidine can have beneficial effects on reducing or preventing diabetes-related complications, as well as preventing altered endothelial function by inflammation. Furthermore, carnosine alleviates diabetic nephropathy by protecting podocyte and mesangial cells. Carnosine has excellent potential to be used as a natural antioxidant in processed foods, since it has been suggested to be absorbed intact through the intestine into the blood. Thus, it is feasible to explore potential health beneficial effects of consumption of carnosine in metabolic diseases.

This study aimed to investigate pro- and anti- inflammatory immune responses mediated via Th17 and regulatory T immune cells, and endothelial activation following 7-day high-salt (HS) loading in young salt-resistant healthy individuals. 30 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). Serum pro- and anti- inflammatory cytokines (INF-γ, TNF-α, IL-6, IL-9, IL-17A, IL-23, IL-10, IL-21, IL-22, TGF-β1), complement component C3a, soluble cell adhesion molecules (sICAM-1, sVCAM-1, E-selectin) and endoglin levels, as well as frequencies of Th17 and regulatory T immune cells (Treg), Th17/Treg ratio and the level of enzymes involved in their activation and differentiation (SGK1 and p38/MAP kinase) were measured before and after 7-day HS diet protocol. 7-day HS diet significantly increased serum level of pro-inflammatory cytokines INF-γ, TNF-α, IL-9 and IL-17A level, but also serum concentration of anti-inflammatory cytokines IL-10 and TGF-β1. Soluble cell adhesion molecules and endoglin level, frequencies of Tregand Th17 cells, Th17/Treg ratio, as well as relative amount of total and phosphorylated p38/MA kinase remained unchanged, while relative amount of total SGK1 significantly increased following 7- day HS diet compared to LS values. There was moderate positive correlation between the frequency of Th17 cells and IL-23 level, and between 24-h urine natriuresis and IFN-γ, and IL- 9. There was strong/moderate positive correlation between relative amount of phosphorylated p38/MAP kinase and sVCAM-1, and endoglin. The increase in serum IL-17A level and increase in relative amount of total SGK1 in PBMCs suggest (at least) initial activation of Th17 cells in response to HS diet, but also an anti-inflammatory response potentially mediated by Treg cells activation and characterized by increase in serum IL-10 and TGF-β level. These results indicate that a short-term 7- day HS diet in healthy salt-resistant individuals promotes low-grade inflammation characterized by early activation of Th17 cells, and concomitant protective anti-inflammatory response of Treg cells.

Predavanje predstavlja trenutne spoznaje o optimalnim vrijednsotima krvnog tlaka u bolesnika s koronarnom arterijskom bolesti.

There is a strong potential of n-3 polyunsaturated fatty acids (n-3 PUFAs) consumption to reduce cardiovascular risk and to prevent adverse outcomes in existing cardiovascular diseases. This study aimed to test if dietary supplementation of n-3 PUFAs in form of enriched hen eggs may modulate serum lipid and fatty acid profile, inflammatory and oxidative stress biomarkers in patients with coronary artery disease (CAD). Forty CAD patients participated in this study ; 20 patients had acute CAD (Ac-CAD) and 20 patients had chronic CAD (Ch-CAD). Control group (N=20) ate three regular hens’ eggs/daily (249mg n-3 PUFAs/day), and n-3 PUFAs group (N=20) ate three n-3 PUFAs enriched hen eggs/daily (1053mg n-3 PUFAs/day) for 3 weeks. Serum n-3 PUFAs concentration significantly increased (in all CAD patients), while total cholesterol and LDL cholesterol and IL-6 (in Ac-CAD patients), as well as total cholesterol and LDL, hsCRP and IL-1a (in all CAD patients) significantly decreased in n-3 PUFAs group. Glutathione peroxidase (GPx) activity significantly decreased. Consumption of three n-3 PUFAs enriched hen eggs for three weeks have favorable effect on fatty acids profile (lower n-6/n-3 PUFAs ratio) and mild anti-inflammatory effect. Since consumption of both regular and n-3 PUFAs eggs had no negative effects on any of the measured parameters, results of the present study also indicate that eggs can be safely consumed in the daily diet of patients with coronary artery disease.

Introduction: Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the arteries supplying the kidneys. Due to low local blood flow, the kidneys mistakenly increase blood pressure of the entire circulatory system. RVH is one type of secondary hypertension. Its most common causes are atherosclerotic renal artery stenosis and fibromuscular dysplasia. Case report: We report a case of a 38-year-old woman, who was admitted to the Department of Cardiovascular Diseases in November 2017 due to acute myocarditis, pulmonary edema and high blood pressure. She was subsequently hospitalized several times for hypertensive pulmonary edema. The last hospitalization was in September 2020 due to cardiac decompensation, unregulated arterial hypertension and deterioration of renal function. We suspected renovascular hypertension and CT angiography of renal arteries was performed. CT showed subocclusion of the right renal artery and subocclusion of the main left renal artery. The patient has physiological variation presented as two left renal arteries. Occlusion of the left iliac internal and external artery was also detected. Echocardiography showed an estimated 40- 45% ejection fraction, left atrial dilatation, mild mitral valve regurgitation and there were no signs of aortic coarctation. She was recommended for stenting left internal iliac and left main renal artery. Conclusion: RVH is an uncommon but potentially remediable cause of hypertension. We should suspect RVH in patients with hypertension that is difficult to control. CT angiography is indicated for diagnosis. Appropriate treatment continues to evolve, but control of hypertension is imperative.

UVOD: Hipertenzija (arterijski tlak >140/90 mmHg) vodeći je uzrok kardiovaskularnih bolesti (KVB) i vodeći uzrok smrti globalno. Prevalencija hipertenzije iznosi 30-45% u odraslih, a čak 60% u osoba starijih od 65 godina. Iako je najčešći pojedinačni faktor rizika za KVB, rijetko se javlja izolirano. Često su uz hipertenziju pridruženi i drugi faktori rizika poput dislipidemije , šećerne bolesti, pretilosti, sedentarnog načina života, pušenja te obiteljske anamneze na KVB, što dodatno utječe na ciljno oštećenje organa. Posljedice neliječene hipertenzije dovode do oštećenja krvnih žila (mikro i makrovaskularna oštećenja) i ciljnih organa (srce, mozak, bubrezi, oči). RASPRAVA: Brojni patofiziološki mehanizmi dovode do nastanka hipertenzije (povećana simpatička aktivnost i posljedična aktivacija renin-angiotenzin-aldosteron sustava (RAAS), oksidativni stres, povećanje cirkulirajućih proupalnih citokina i endotelna disfunkcija), ali isti ti mehanizmi dovode i do progresije KVB i mikrovaskularne bolesti. Starenje, kao i povišen arterijski tlak, dovode do stanjenja elastina krvnih žila i pojačano odlaganje kolagena što posljedično dovode do povećane krutosti arterija i endotelne disfunkcije koja dovodi do smanjenja autoregulatornih procesa (nepovoljan odnos vazodilatatora poput dušikova oksida i prostaglandina E te vazokonstriktora poput endotelina i angiotenzina II). Zbog povećane krutosti aorte dolazi do povećane brzine pulsnog vala, a time i do pojave povratnog vala u kasnoj sistoli što dovodi do dodatnog povišenja sistoličkog krvnog tlaka (SKT) i smanjenja dijastoličkog tlaka (DKT). Povišenje SKT i DKT dovodi do progresije aterosklerotske (ATS) bolesti koronarnih arterija a sniženje DKT do kompromitacije koronarne perfuzije (jer se 85% perfuzije lijeve klijetke (LK) događa u dijastoli). Iako koronarne arterije imaju sposobnost autoregulacije, zbog endotelne disfunkcije dolazi i do njenog oštećenja i smanjenje vazodilatacije. Te promjene dovode do povećanog rizika nastanka i/ili progresije ishemijske bolesti srca. Povišenje SKT dovodi do povećanog naknadnog opterećenja (afterload) i koncentrične hipertrofije LK što je kompenzacijski mehanizam kako bi se smanjio povišen stres na zidu miokarda (wall stress). Hipertrofija LK sama po sebi izaziva povećan metabolizam i potrošnju kisika, a uz ATS koronarnih arterija dolazi do nedovoljne perfuzije miokarda i neravnoteže između opskrbe i potrošnje kisika i hranjivih tvari. Daljnjom progresijom hipertenzivne bolesti srca može doći do dilatacije LK a potom i srčanog popuštanja. Također, HLK dovodi do poremećaja relaksacije miokarda, odnosno poremećene dijastoličke funkcije. Zbog povećanog tlaka punjenja LK, dolazi do dilatacije lijevog atrija a time i povećanim rizikom za nastanak fibrilacije atrija, najčešće srčane aritmije. Za dokazivanje hipertenzivne bolesti srca koristimo EKG, RTG srca i pluća, UZV srca i laboratorijske nalaze. Iako ima nisku senzitivnost, EKG može biti vrlo koristan u procjeni HLK (Sokolow–Lyon i Cornellovi kriteriji). Ehokardiografija je zlatni standard za potvrdu dijagnoze, a ultrazvučne karakteristike hipertenzivne bolesti srca su: koncentrična hipertrofija LK, dijastolička disfunkcija te uvećanje lijevog atrija. Ako se pojave, najčešći simptomi hipertenzivne bolesti srca su: umor, zaduha, bol u prsima. ZAKLJUČAK: Kada govorimo o srcu te krvnim žilama, hipertenzivna i ishemijska bolest srca su najčešće posljedice neliječene hipertenzije što dovodi do visoke smrtnosti. U dijagnostici hipertenzivne bolesti srca centralnu ulogu ima ultrazvuk srca. U liječenju osim farmakoloških lijekova (lijekovi izbora bi bili ACE inhibitori i blokatori kalcijskih kanala, te diuretici), potrebna je promjena životnih navika (fizička aktivnost, prestanak pušenja, ishrana bogata vlaknima, voće i povrćem, smanjen unos soli, redukcija tjelesne težine) te modifikacija i liječenje ostalih rizičnih čimbenika (dislipidemija, dijabetes). Prema preporukama ESH/ESC ciljne vrijednosti tlaka su

Aim: Present study aimed to determine the effect of n-3 PUFAs enriched hen eggs consumption on microvascular vasodilation, microvascular responsiveness range to a stress challenge and markers of oxidative stress in competitive athletes. Materials and Methods: 23 competitive athletes were divided to Control group (N=9) who ate three regular hens’ eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs group (N=14) who ate three n-3 PUFAs enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Endothelium- dependent (post-occlusive reactive hyperemia, PORH ; and iontophoresis of acetylcholine, AChID) and endothelium-independent responses (iontophoresis of sodium nitroprusside, SNPID) of skin microvascular blood flow was assessed by laser Doppler flowmetry in pre- and post- acute exhausting exercise (AEE) sessions. Blood pressure (BP), body composition, body fluid status, serum lipid and free fatty acids profile, markers of oxidative stress (TBARS ; thiobarbituric acid reactive substances) and antioxidative defense (FRAP ; ferric-reducing ability of plasma and serum antioxidant enzymes activity), were measured before and after respective dietary protocol. Results: Serum n-3 PUFAs significantly increased, n-6/n-3 ratio decreased (by 27%), PORH and AChID at rest were significantly enhanced, and SNPID at rest remained unchanged in n-3 PUFAs group, while none was changed in Control group. BP, body composition and body fluid status were not changed in any group. TBARS and FRAP remained unaffected by diet protocol in both groups, while serum GPx and SOD (but not CAT) activity significantly decreased in n-3 PUFAs, and remained unaltered in Control group. PORH, AChID and SNP were significantly reduced post-AEE, in both groups compared to pre-AEE measurement, both before and after respective diet protocol. Only AChID responsiveness range to AEE (ΔAChID) significantly increased following n-3 PUFAs consumption. Conclusion: n-3 PUFAs functional food consumption contributes to enhanced microvascular endothelial function at rest, as well as to its adaptation to the AEE in competitive athletes. (Funded by the European Structural and Investment Funds grant for the Croatian National Scientific Center of Excellence for Personalized Health Care, University of Josip Juraj Strossmayer Osijek - grant #KK.01.1.1.01.0010).

There is a strong potential of n-3 polyunsaturated fatty acids (n-3 PUFAs) consumption to reduce cardiovascular risk and to prevent adverse outcomes in existing cardiovascular diseases. This study aimed to test if dietary supplementation of n-3 PUFAs in form of enriched hen eggs may modulate serum lipid and fatty acid profile, inflammatory and oxidative stress biomarkers in patients with coronary artery disease (CAD). Forty CAD patients participated in this study ; 20 patients had acute CAD (Ac- CAD) and 20 patients had chronic CAD (Ch-CAD). Control group (N=20) ate three regular hens’ eggs/daily (249mg n-3 PUFAs/day), and n-3 PUFAs group (N=20) ate three n-3 PUFAs enriched hen eggs/daily (1053mg n-3 PUFAs/day) for 3 weeks. Serum n-3 PUFAs concentration significantly increased (in all CAD patients), while total cholesterol and LDL cholesterol and IL-6 (in Ac-CAD patients), as well as total cholesterol and LDL, hsCRP and IL-1a (in all CAD patients) significantly decreased in n-3 PUFAs group. Glutathione peroxidase (GPx) activity significantly decreased. Consumption of three n- 3 PUFAs enriched hen eggs for three weeks have favorable effect on fatty acids profile (lower n-6/n-3 PUFAs ratio) and mild anti-inflammatory effect. Since consumption of both regular and n-3 PUFAs eggs had no negative effects on any of the measured parameters, results of the present study also indicate that eggs can be safely consumed in the daily diet of patients with coronary artery disease.

Presentation of original research article Anti- Inflammatory Potential of n-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption in Improving Microvascular Endothelial Function of Healthy Individuals—Clinical Trial by Ana Stupin, Martina Mihalj, Nikolina Kolobarić, Petar Šušnjara, Luka Kolar, Zrinka Mihaljević, Anita Matić, Marko Stupin, Ivana Jukić, Zlata Kralik, Manuela Grčević, Gordana Kralik, Vatroslav Šerić and Ines Drenjančević. Funding: #KK.01.1.1.01.0010 European Structural and Investment Funds grant for the Croatian National Scientific Center of Excellence for Personalized Health Care, University of Josip Juraj Strossmayer Osijek

U predavanju se prikazuje značaj varijabilnosti srčanog ritma kod bolesnika s arterijskom hipertenzijim. Prikazani su klinički indikatori abnormalne kardijalne autonomne funkcije te učinci nefarmakoloških mjera i pojedinih skupina antihipertenziva na varijabinost srčanog ritma.

Objective: We have earlier reported that 7-day high-salt (HS) intake increases oxidative stress and impairs microvascular endothelium- dependent vasodilation in young healthy individuals, independently of blood pressure (BP) changes. The aim of the present study was to test whether such disturbed oxidative balance has direct adverse effect on microvascular endothelial function by functionally testing if administration of vitamins C and E during 7-day HS diet will prevent observed alterations in endothelium- dependent vasodilation of skin microcirculation in healthy individuals. Materials and Methods: 51 young healthy individuals of both sexes (26 women and 25 men, age ranged 18-24) were assigned to a 7-day low- salt diet (

Introduction: Coronary artery disease (CAD), also known as coronary heart disease (CHD) or ischemic heart disease (IHD), involves the reduction of blood flow to heart muscle due to build-up of plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction and sudden cardiac death. Case report: We report a case of a 60-year-old woman, who was taken to the accident and emergency room. For two months she had been experiencing a severe chest pain during physical effort. In time, ailments progressed and eventually her symptoms started to occur even in contact with the cold air. The pain subsides when she rests. She did not have any respiratory problems nor any signs of dyspnea. She had multiple risk factors for coronary disease such as unregulated hypertension and hyperlipidemia, also her family's medical history was positive to cardiovascular diseases. Earlier this year she has developed hypertensive crisis that caused subarachnoid bleeding. In her reports, chest X-ray was clean and there were no signs of ischemia on ECG. Cardioselective enzymes were within reference interval, but because of her significant anamnesis we suspected coronary artery disease. Echocardiography has been made, which was clean with an estimated 64% ejection fraction. Coronarography showed significant stenosis of LAD. She got 2 stents and therapy for her coronary disease was prescribed. Conclusion: Regardless of today's technology techniques which are very specific in discovery of coronary diseases, such as ECG, echocardiography, X-ray and laboratory reports, the rule of taking anamnesis is equally important in recognition of coronary disease and its future treatment.

Functional food is a food of natural origin that contains ingredients beneficial for human health when consumed in normal daily amounts. Potential beneficial effects of dietary daily intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) on various cardiovascular parameters are currently intensively investigated, particularly their role in vasoreactivity in macrocirculation and hemorrheological characteristic of the blood (for possible antithrombotic and atherosclerotic effects) and microcirculation (such as coronary and systemic microcirculation), investigating molecular targets related to endothelial function, e.g. endothelial or vascular smooth muscle cell ion channels, components of cellular and systemic oxidative stress/antioxidative system and the vasoactive effects of eicosanoids-metabolites of n-3 PUFAs and arachidonic acid. Inflammation underlies all cardiometabolic diseases. It has been suggested that n-3 PUFAs dietary intake can significantly attenuate inflammatory processes, contributing to maintaining healthy vascular function. Integrating the knowledge on molecular and physiological mechanisms potentially involved in vascular function is important for understanding etiopathogenesis of cardiovascular diseases and translation of research to clinical settings, to obtain medical treatment based on evidences. Hereby, the recent data on the effects of dietary n-3 PUFAs intake in form of enriched eggs on vascular function and immune system in healthy persons and cardiovascular patients is going to be presented. Acknowledgement: supported by European Structural and Investment Funds, grant for the Croatian National Scientific Center of Excellence for Personalized Health Care, University Josip Juraj Strossmayer Osijek #KK.01.1.1.01.0010.

Objectives: We aimed to assess whether a 7-day high-salt (HS) diet affects endothelium- dependent and/or endothelium-independent microvascular function in the absence of changes in arterial blood pressure, and to determine whether such microvascular changes are associated with changes in body composition and fluid status in healthy young humans. Materials and Methods: Fifty-three young healthy individuals (twenty-eight women and twenty-five men) were assigned to a 7-day low- salt (LS) diet (

Predavanje se osvrće na pojavu izolirane sistoličke hipertenzije u mladih ljudi, na patofiziološke mehanizme te potrebu za liječenjem.

Introduction: High-salt (HS) intake, high levels of angiotensin II and increased sympathetic (SNS) activity are all injurious to the cardiovascular (CV) system, and play a role in a multitude of CV diseases. In recent years it became evident that HS dietary intake affects vascular and particularly endothelial functions even in the absence of changes in blood pressure (BP) in healthy individuals. HS intake suppress renin-angiotensin system (RAS) in healthy individuals, but it is still not elucidated how HS intake affects SNS activity in healthy population in the absence of BP changes (does it inhibit or potentiate SNS activity). The aim of our project is to assess SNS/parasympathetic (PSNS) activity by measurement of heart rate variability (HRV), and level of catecholamines and their metabolites in 24h urine sample before and after HS diet protocol in young healthy individuals. Methods: 10 young healthy men were assigned to 7-days low salt (LS) diet (

Inflammation and oxidative stress are now recognized as major factors involved in the pathogenesis of different diseases, like cardiovascular diseases or overweight/obesity. Increased consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) is associated with decreased level of oxidative stress and anti- inflammatory effects possibly due to reduced arachidonic acid (AA)-derived eicosanoids reduced triglyceride levels, and inhibition of platelet aggregation. Most studies on the effect of n-3 PUFAs were performed on chronic patients and with the use of n-3 PUFAs in the form of supplements (capsules). The relationship between human health and food and the way in which food can affect the maintenance and improvement of human health is increasingly in the focus of the researchers. Currently, Scientific Center of Excellence for Personalized Health Care Osijek investigates the influence of n-3 PUFA enriched eggs on the endothelial function of the blood vessels and the change of the level of oxidative stress in cardiovascular patients and in healthy, young people and athletes. These studies have so far shown that n-3 PUFAs lowers the level of oxidative stress in healthy young people and have a positive effect on the microcirculation even in people with normal endothelial function, suggesting their protective effects in cardiovascular diseases.

For its potential positive effect on sport performance, N-3 polyunsaturated fatty acids (n-3 PUFAs), are one of often used nutritional supplements of athletes. Beyond its potential beneficial effects on muscles, fatigue and VO2 max consumption, n-3 PUFAs effect on vascular function is widely investigated, particularly on macrocirculation. Even though majority of performed studies reported an increase in post- occlusive reactive hyperemia of brachial artery in healthy subjects after consumption of n-3 PUFAs measured by flow mediated dilation, some studies reported inconsistent results probably due to its heterogeneous design related to the amount and length of n-3 PUFAs intake, as well as type of supplementation. Limited number of studies investigated the effect of n-3 PUFAs consumption on microvascular function, and result of these studies are even more unclear. Recently we have shown significantly enhanced post-occlusive reactive hyperemia of skin microcirculation in young sedentary healthy population who consumed n-3 PUFAs enriched eggs for three weeks. But still, there is a paucity of data on the effect of n-3 PUFAs consumption on microvascular reactivity and endothelial function in particular in athletes. Since we also showed beneficial effects of n-3 PUFAs on inflammation and oxidative stress in sedentary subjects which is one of the possible causes of enhanced microvascular reactivity, it is reasonable to believe it would have similar effect in athletes since acute exercise session leads to incensement of oxidative stress and inflammation. Moreover, new concept of n-3 PUFAs intake in the form of functional food (e.g. n-3 PUFAs enriched hen’s eggs) raises interest, especially since hen’s eggs are indispensable part of sports diet. While there are strong evidences that n-3 PUFA-s consumption can reverse endothelium-dependent vasodilation in cardiovascular diseases, it still remains to elucidate whether they can improve already “healthy” endothelium in athletes and investigate what would be potential mechanisms mediating such effect.

Introduction: High salt dietary intake (HS) is known causal factor of endothelial dysfunction, even without increases in arterial blood pressure. The aim of this study was to present our current work on the underlying mechanisms of endothelial dysfunction occurring in HS diet, related to increased oxidative stress, in healthy animals and young healthy humans. Methods: Functional studies on the mechanisms of microvessel’s reactivity (endothelium- dependent and endothelium-independent) as well as molecular (mRNA ; protein expression) and biochemical analyses (enzymatic activity, flow- cytometry, direct fluorescence) on the biomarkers of vascular and systemic oxidative stress were performed in healthy normotensive young men and women (N = 10–15 (per set ; average age 21 yrs) and healthy normotensive Sprague-Dawley male rats 11-weeks old (N = 7–10/per group) on a HS and low-salt (LS) diet. Results: Human:HS diet impairs endothelium- dependent, but not endothelium-independent vasodilation in skin microcirculation (post-occlusive reactive hyperemia (PORH) ; ACH vs. SNP) and increases TXA2 production in healthy women (J Physiol 2015 ; 593(24):5313–24). HS diet significantly increased basal ROS production in monocytes. HS diet significantly increased oxidative stress level (TBARS) and decreased antioxidant capacity (FRAP). PORH and FRAP positively correlated, while PORH and TBARS negatively correlated. There was negative correlation between salt intake and FRAP and between salt intake and PORH. 7-day HS diet did not induce significant change in arterial blood pressure, or in body composition or fluid status in young healthy population. Plasma renin activity (PRA) and serum aldosterone level in humans are suppressed by HS diet. Animals: Attenuated flow-induced dilation of cerebral resistance arteries (MCA) is related to increased vascular oxidative stress and NO pathway in rats on a short-term HS diet (J Physiol 2016 ; 594(17):4917–31). HS diet suppresses flow- induced NO production in MCA, which is restored by superoxide scavenging (AJP 2018 ; 315(3):H718-H730). Brain blood vessels antioxidant enzyme expression is decreased in HS diet (Gpx4), while HIF-1alpha and COX-2 protein levels are increased, possibly related to increased oxidative stress caused by HS diet and reversed by TEMPOL in vivo. Oxidative stress in leukocytes isolated from blood and peripheral lymph nodes is increased. Conclusions: HS diet significantly alters microvascular reactivity in young healthy normotensive women, without changes in blood pressure and in animal model of normotensive SpragueDawley rat. HS diet significantly reduces antioxidant capacity and increases oxidative stress markers, leading to switch in pathways mediating vasodilation, which can be associated with microvascular dysfunction, confirmed in both types of studies. Microvascular dysfunction precedes changes in blood pressure. Funded by grants from Croatian Science Fundation: RAS-AdrenOX (IP-2016-06- 8744, PI Ana Stupin) and VELI-Athero (IP-2014- 09-6380, PI Ines Drenjancevic.

Microcirculation is a highly regulated part of the circulatory system and various dietary factors could affect its function, exerting positive or negative effects. For example, high salt (NaCl) dietary intake is a well known risk factor for the development of hypertension, while microvascular dysfunction develops even without changes in arterial blood pressure. Ultimately, that leads to organ damage and increases the risk of cardiovascular events. Potential mechanisms include decreased NO bioavailability as well as changes in balance of vasoactive eicosanoids, such as metabolites of arachidonic acid, all due to impaired vascular antioxidative mechanisms. On the other hand, new studies demonstrate potentialy protective effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) food intake, as counter-balancing protective arm of vasoactive metabolites potentially alleviating oxidative stress. Animal models and isolated organs studies enable an insight into potential molecular mechanisms and cross talks involved, while in situ human studies provide integrated information on body function and might have clinical implications. Hereby, some recent findings in the vascular tone regulation mechanisms, from assessment of vascular reactivity in response to high salt as a foe, or increased dietary n-3 PUFAs intake (in the form of n-3 PUFAs enriched eggs) as a beneficiary nutrients will be presented. Acknowledgement: This work was supported by European Structural and Investment Funds, grant for the Croatian National Scientific Center of Excellence for Personalized Health Care, University Josip Juraj Strossmayer Osijek, #KK.01.1.1.01.0010. and partially by Croatian Science Foundation grant #IP-2016-06-8744 (RAS-AdrenOX) and Croatian Science Foundation grant #IP-09-2014-6380 (V-ELI Athero).

A growing body of evidence indicate that high- salt (HS) intake is highly detrimental to vascular and endothelial function, even in the absence of changes in arterial blood pressure (BP) level. Studies in healthy individuals have unambiguously demonstrated that HS diet impairs flow-mediated dilation of brachial artery, independently of BP changes in healthy individuals. Recent studies that were more focused on microvascular function yielded consistent results by reporting impaired post- occlusive reactive hyperemia (marker of general microvascular reactivity), acetylcholine- induced dilation (endothelium-dependent dilation) and local heating-induced vasodilation (considered NO-mediated response) of forearm skin microcirculation following 7- days HS loading in healthy individuals. Several potential mechanisms were suggested to mediate such BP-independent HS diet-induced impairment of vascular and endothelial function e.g. suppression of renin-angiotensin system (RAS), increased oxidative stress level, changes in sympathetic activity, inflammation and endothelial-leukocyte activation, fluid retention, osmotically inactive sodium storage, endothelial glycocalyx alterations etc. Our recent study that investigated interaction of HS loading, RAS suppression and possible fluid retention in healthy individuals demonstrated that observed microvascular reactivity impairment due to 7-days HS loading was independent of BP changes, body composition or fluid status changes, but associated with increased salt intake and suppressed RAS. An increasing number of studies in animal model indicate that increased oxidative stress plays a central role in HS diet-induced vascular damage. On the other hand, human studies did not contribute much to the understanding of the role of oxidative stress in mediating adverse effect of HS intake on vascular/endothelial function. Thus, the next key step in understanding interaction between HS loading and endothelium in healthy individuals is to investigate the direct influence of short-term HS intake on measurable parameters of oxidative stress level, and to examine whether potentially increased oxidative stress level is directly functionally associated with altered microvascular and endothelial function. (HRZZ #IP-2016-06-8744).

Little is known about the risk of sudden death related to exercise in young athletes, and whether there are more benefits than damage from exercise. By recent studies, there is 2.5 fold increased risk of sudden death in competitive athletes than sedentary peers. There is also proved that most common causes of sudden death are silent cardiovascular diseases. A broad spectrum of cardiovascular diseases can cause sudden death, including congenitaland inherited disorders. Hypertrophic cardiomyopathy is implicated as the prime cause of sport-related cardiac arrest (more than one- third), and other common causes include congenital coronary artery anomaly. Myocarditis, aortic rupture, mitral valve prolapse, arrhytmogenic RV cardiomyopathy, conduction system abnormities are less common. Most of these conditions (up to 60% of sudden deaths) can be diagnosed or suspected with ECG. In addition to ECG, athlete’s history and detailed physical examination is necessary to do. Complete personal and family history is important because of genetically determinated diseases, and it is considered positive when close relative (aged

It has been proposed that inflammation has an important role in the mechanisms underlying endothelial dysfunction induced by high-salt (HS) intake, and that the leukocyte-endothelial cell interactions are important for this process. This study aimed to assess the effect of 7-days salt intake modulation (low salt – LS and HS diet) on leukocytes activation defined by CD11a expression (part of LFA-1/Leukocyte Function Antigen 1, which is ligand of ICAM-1-5/Intercellular Adhesion Molecules 1-5) using flow cytometry in young healthy women. 15 young healthy women participated in this study. After initial 7-days LS diet (

Arterijska hipertenzija (AH) vodeći je uzrok pobola i smrti u svijetu, pa tako i u Hrvatskoj. Prema podacima EH-UH 1 istraživanja, koje je završeno prije 15 godina, prevalencija AH- a iznosila je 37%, uz vrlo lošu kontrolu liječenja - oko 20%. Jedan od glavnih razloga velike prevalencije i loše kontrole je prekomjeran unos kuhinjske soli koji prema rezultatima istraživanja u Hrvatskoj iznosi više od 11 grama dnevno. Podaci su bili temelj za izradu Strateškoga plana Vlade RH za smanjivanje unosa kuhinjske soli. Cilj projekta je: 1) na temelju podataka iz arhive prethodno provedenog istra živanja (EH-UH1) pozvati na kontrolni pregled sve ispitanike, pratiti klinički tijek bolesti i njen ishod ovisno o ulaznim pokazateljima ; 2) na način kako je rađeno i u EH- UH1, u EH-UH2 randomizirati novi uzorak opće populacije u Hrvatskoj, koristiti isti upitnik i način pregleda, mjerenja arterijskoga tlaka (AT) i određivanja pridruženih čimbenika rizika te odrediti prevalenciju, svjesnost, liječenje i kontrolu hipertoničara kao i dinamiku kretanja hipertenzije u Hrvatskoj tijekom 10 godina ; 3) u obje skupine ispitanika (post - EH- UH 1 i tijekom EH-UH 2) odrediti unos kuhinjske soli mjerenjem 24-satne na triurije ; 4) u istom uzorku urina odrediti količinu joda s ciljem utvrđivanja neškodljivosti smanjivanja unosa kuhinjske soli. Rezultati će omogućiti utvrđivanje najznačajnijih čimbenika za razvoj AH-a i njihove povezanosti s kliničkim ishodima.