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Longitudinal myocardial function (LMF) may be impaired while systolic function is still normal. We investigated relationship between LMF and hypertensive organ damage in newly diagnosed stage I hypertensive patients. A total of 57 patient with never treated stage I hypertension and 48 matched healthy control subject were enrolled in the study. Conventional 2-D, Doppler and tissue wave Doppler imaging (TDI) echocardiography were used. LMF was evaluated by the septal and lateral strain (S) and strain rate (SR) measurements. Hypertensive complications were evaluated by the urine microalbumin levels and retinal examination. A multivariate regression analysis was perfomed to assess the relation between the variables. Ejection fraction, mid-wall fractional shortenning, systolic movement rates (TDs) in TDI were similar both in hypertensive and control groups. In patients with left ventricular hypertrophy, septal TDs (7.29 +/- 1.28 vs. 8.06 +/- 1.19 cm, P = 0.03), lateral TDs (8.46 +/- 1.83 vs. 9.87 +/- 2.42 cm, P = 0.01) and lateral S (-13.02 +/- 7.83 vs. -18.86 +/- 8.60%, P = 0.01) values were significantly lower. Septal S (-13.67 +/- 3.52 vs. -19.09 +/- 5.96%, P < 0.01) and SR (-0.83 +/- 0.29 vs. -1.22 +/- 0.28 1/S, P < 0.01) were significantly decreased in hypertensive patients with microalbuminuria. Septal S value was also significantly decreased in patients with retinopathy (-14.76 +/- 5.55 vs. -20.20 +/- 5.44%, P = 0.01). Multivariate analysis showed that only septal and lateral S values were independent factors for the retinopathy and left ventricular hypertrophy, respectively. In hypertensive patients, LMF established by the measurement of S and SR, might be impaired and also related with end organ damage while global circumferential function is preserved. [ABSTRACT FROM AUTHOR]

Background: P-wave dispersion (Pd), corrected P-wave dispersion (Pdc), QT-wave dispersion (QTd), and corrected QT-wave dispersion (QTdc) parameters were not assessed in Turner Syndrome (TS) before. The aim of this study is to investigate the cardiac arrhythmogenic potential in patients with TS. Methods: Thirty-one patients with TS and 30 healthy women were enrolled in the study. For this purpose 12-lead electrocardiogram (ECG) and 24-hour ambulatory ECG recordings were performed. Results: Pd, Pdc, QTd, and QTdc were significantly higher in patients with TS. On 24-hour ambulatory ECG recording, the mean heart rate (HR) was higher, while the mean of all RR intervals between normal beats (MeanNN), the standard deviation of all the RR intervals (SDNN), the square root of the mean of the squared differences of two consecutive RR intervals (rMSSD), and the percentage of the beats with consecutive RR interval difference more than 50 milliseconds (pNN50) were lower in TS. Conclusion: There were significant increases in Pd, Pdc, QTd, and QTdc in patients with TS and they may be features of the disease. The frequency of supraventricular arrhythmias was increased. There also was a significant deterioration of sympathetic and parasympathetic components of autonomic function as assessed by heart rate variability (HRV) in Turner patients. [ABSTRACT FROM AUTHOR]

Aspirin (acetylsalicylic acid) is a powerful antiplatelet agent used in prevention of atherothrombotic vascular events. However, antiplatelet effect of aspirin is not uniform and some patients could not benefit from aspirin. These patients are clinically called as aspirin resistant or aspirin non-responders. Aspirin resistance could be determined by: bleeding time, optical aggregometry, PFA-100 (Platelet Function Analyzer), Ultegra-RPFA (Rapid Platelet Function Assay), activated aggregation time, whole blood aggregometry, platelet aggregate ratio, flow cytometry, measurements of platelet surface proteins and blood or urine thromboxane B2 levels. Mechanisms of aspirin resistance have not been elucidated yet. There is evidence that aspirin resistance increases clinical cardiovascular events. Adequate additional therapies may reduce atherothrombotic risks and major cardiovascular events rate in aspirin resistant subjects. However, we need further studies to decrease major cardiovascular events risk in aspirin resistant subjects and to optimize antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Hypertension is one of the most common noncommunicable chronic diseases and is an important risk factor for vascular complications. The prevalence of hypertension is very high worldwide, and it is still increasing in low- and middle-income countries. Although some improvements were reported in high-income countries in recent years, there is still much to do to overcome hypertension and its complications. Identically, hypertension is a severe public health issue in Turkey. Approximately one third of the adult population has got hypertension but almost half is unaware of the disease. Children and youths are also affected by the burden of hypertension. Increased body mass index and obesity frequently accompany hypertension in children and adolescents. Major contributors to the disease burden appears to be consumption of high amounts of dietary sodium, lack of appropriate physical activity, increasing weight and obesity. In the last decades, an improvement at disease awareness has been achieved but blood-pressure control rates are still low in Turkey. Traditional and natural products, including lemon juice and garlic, are very popular among patients with concerns regarding medications' side effects. Patients' adherence to therapy differs between regions and increases in parallel with high education level. Decreasing daily salt intake has been shown to reduce the prevalence of hypertension substantially and to prevent cardiovascular and cerebrovascular deaths in a cost effective manner in projection studies. Finally, improving education of patients, which has positive effects on disease awareness, treatment adherence, and blood-pressure control rates, should be considered., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

The aim of this study was to investigate the possible relationship between worse clinical outcomes and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in hospitalized COVID-19 patients. A total of 247 adult patients (154 males, 93 females; mean age: 51.3 ± 14.2 years) hospitalized for COVID-19 as confirmed by polymerase chain reaction (PCR) were retrospectively reviewed. Demographic and clinical characteristics and laboratory parameters were analyzed using various statistical modeling. Primary outcomes were defined as the need for intensive care unit (ICU), mechanical ventilation, or occurrence of death. Of the patients, 48 were treated in the ICU with a high flow oxygen/noninvasive mechanical ventilation (NIMV, n = 12) or mechanical ventilation (n = 36). Median length of ICU stay was 13 (range, 7-18) days. Mortality was seen in four of the ICU patients. Other patients were followed in the COVID-19 services for a median of 7 days. There was no significant correlation between the primary outcomes and use of ACEIs/ARBs (frequentist OR = 0.82, 95% confidence interval (CI) 0.29-2.34, p = 0.715 and Bayesian posterior median OR = 0.80, 95% CI 0.31-2.02) and presence of hypertension (frequentist OR = 1.23, 95% CI 0.52-2.92, p = 0.631 and Bayesian posterior median OR = 1.25, 95% CI 0.58-2.60). Neutrophil-to-lymphocyte ratio (NLR) and D-dimer levels were strongly associated with primary outcomes. In conclusion, the presence of hypertension and use of ACEIs/ARBs were not significantly associated with poor primary clinical outcomes; however, NLR and D-dimer levels were strong predictors of clinical worsening., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Low molecular weight heparin (LMWH) may provide beneficial effects on outcomes of COVID-19. We aimed to examine the impact of LMWH treatment on clinical outcomes (duration of hospitalization, admission to intensive care unit, the requirement for mechanical ventilation, and death) of COVID-19 patients with normal D-dimer levels at admission., Background: Coronavirus disease-2019 (COVID-19) predisposes patients to arterial and venous thrombosis., Methods: In this retrospective, multicentre and observational study we analysed the data of 308 confirmed COVID-19 patients with normal D-dimer levels at initial admission. After propensity score matching (PSM) patients were grouped; Group 1; patients who received LMWH with D-dimer ≤0.5 mg/L, Group 2; patients who received LMWH after D-dimer levels exceeded 0.5 mg/L, and Group 3; patients who did not receive LMWH., Results: After PSM, each group comprised 40 patients. The patients in Group1 had the best clinical outcomes compared to the other groups. Group 3 had the worst clinical outcomes (p<0.005). The benefit of LMWH increased with early prophylactic therapy especially when started while the D-dimer levels were ≤0.5 mg/L., Conclusion: Our results strongly suggest that proactive LMWH therapy improves clinical outcomes in hospitalized COVID-19 patients even with normal D-dimer levels (≤ 0.5 mg/L) (Tab. 3, Fig. 2, Ref. 34).

We aimed to investigate whether or not cardiotrophin-1 (CT-1) can be used as a predictor of sinus rhythm constancy in patients with atrial fibrillation (AF) converted to sinus rhythm. Thirty two patients with AF (48-78 years), without any structural heart disease were enrolled for the study. The control group consisted of 32, age and gender matched healthy persons. Measurements of CT-1 were made after transthoracic and transesophageal echocardiography prior to cardioversion (CV). Relapses of AF were investigated by monthly electrocardiograms (ECGs) and ambulatory ECGs at 1st, 3rd, and 6th month. At the end of 6th month, measurements of CT-1 were repeated. At the beginning patients with AF had increased CT-1 levels when compared to controls (0.94 ± 0.32 pg/mL vs. 0.30 ± 0.12 pg/mL, [p < 0.001]). At the end of follow-up of the 32 patients, 17 (53%) had AF relapse. Age, initial duration of AF, left ventricle diameters, ejection fraction, left atrium appendix flow rates were similar among patients with and without AF relapse. However, basal left atrium diameter (4.24 ± 0.14 cm vs. 4.04 ± 0.22 cm, p = 0.005), pulmonary artery pressure (32.82 ± 5 vs. 28.60 ± 6.23 mmHg, p = 0.004) and CT-1 values (1.08 ± 0.37 vs. 0.82 ± 0.16 pg/mL, p = 0.02) were significantly increased in patients with AF relapse. Furthermore, patients with relapsed AF had higher CT-1 levels at 6th month when compared to those in sinus rhythm (1.00 ± 0.40 vs. 0.71 ± 0.23 pg/mL). We conclude that post-CV, AF relapses are more frequent among patients with increased baseline CT-1 levels, and CT-1 may be a potential predictor of AF relapse.

Aims: The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets., Methods and Results: Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKβ) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2- (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls., Conclusions: There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aspirin has long been the mainstay of primary and secondary prevention against myocardial infarction and ischemic cerebrovascular events. However, the incremental value of aspirin for primary prevention has recently been subject to debate given data from recent large clinical trials, as the net clinical benefit is small. In secondary prevention, aspirin is still strongly recommended. Efforts in obtaining more efficient antiplatelet agents and to reduce cardiovascular morbidity and mortality have led to the development of new adenosine diphosphate (ADP) receptor antagonists, which are superior to clopidogrel. New generation antiplatelet drugs i.e. prasugrel and ticagrelor aim to reduce atherothrombotic events, mortality and stent thrombosis, as well as overcome low- or non-response to clopidogrel. Further agents with antiplatelet properties are being investigated at present. This overview aims to give insights into the rapidly changing field of antiplatelet strategies in cardiovascular diseases.

Background: Cigarette smoking may increase platelet aggregation and cause atherothrombotic cardiovascular events. We aimed to investigate the impact of cigarette smoking on platelet function in patients with ischemic coronary heart disease (CHD)., Methods: Twenty patients with ischemic stable CHD under aspirin therapy (300 mg/d), who continue to smoking despite all warnings, and 20 nonsmokers with CHD are enrolled in the study. Platelet function is studied at the morning, before and 15 minutes after the first cigarette, by the Platelet Function Analyzer (PFA)-100, with collagen and epinephrine and collagen and adenosine diphosphate cartridges. Post aspirin platelet hyperactivity is defined as having a closure time (CT) shorter than 186 seconds despite regular aspirin intake. Serial CT measurements are analyzed by paired samples t test., Results: Persistent platelet activity was present in 4 smoker (20%) and 3 nonsmoker (15%) patients at the beginning. Platelet activity measured by the PFA-100 is been increased significantly after cigarette smoking (P = .004). Shorter CTs were determined after smoking in all patients with and without baseline persistent platelet activity, and 4 more participants became aspirin nonresponder (P = .004). No significant differences in demographic, hematological, and biochemical parameters were determined between aspirin responders and nonresponders., Conclusions: We determined that cigarette smoking may increase platelet aggregation in patients with ischemic CHD in an aspirin nonresponsive manner. Our results emphasize the importance of quitting cigarette smoking in patients with CHD.

Nuclear factor kappa B (NFκB) is a transcription factor belonging to 'Rel' family that represents a crucial intracellular signal transduction system involved in several inflammatory diseases including atherosclerosis. Activation of NFκB mediated signal transduction has been established at different stages of atherosclerosis, beginning from plaque formation to its destabilization and rupture. The NFκB pathway is also involved in angiogenic, apoptotic and neoplastic processes. Experimental studies indicate that inhibition of these pathway may reduce inflammatory burden. The development of natural or pharmaceutical, selective and specific inhibitors of NFκB pathway over IκB kinase α or β, may ultimately prove to be promising anti-atherosclerotic, anti-inflammatory, antiangiogenic and antiapoptotic therapeutic instruments that could potentially reduce inflammation, attenuate atherogenesis and prevent its complications., (Copyright © 2011. Published by Elsevier Ltd.)

The CD40-CD40L system is a pathway which is associated with both prothrombotic and proinflammatory effects. CD40 and its ligand were first discovered on the surface of activated T cells, but its presence on B cells, antigen-presenting cells, mast cells, and finally platelets, is evident. The soluble form of CD40L (sCD40L) is derived mainly from activated platelets and contributes to the pathophysiology of atherosclerosis and atherothrombosis. Indeed, sCD40L has autocrine, paracrine, and endocrine activities, and it enhances platelet activation, aggregation, and platelet-leucocyte conjugation that may lead to atherothrombosis. It has even been suggested that sCD40L may play a pathogenic role in triggering acute coronary syndromes. Conversely, blockade of this pathway with anti-CD40L antibodies may prevent or delay the progression of atherosclerosis. Concentrations of sCD40L also predict risk of future cardiovascular disease in healthy women and clinical outcomes in patients with acute coronary syndromes. However, there are controversial and uncertain points over the application of this biomarker to clinical cardiology. In this review, we provide an overview of potential implications of CD40-CD40L signalling and sCD40L as a biomarker in patients with atherosclerotic vascular diseases.

Importance of the Field: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1 - 2% of the population. Despite several developments in antithrombotic, antiatherosclerotic and device-based cardiac therapies, few noteworthy antiarrhythmic drugs have been developed., Areas Covered in This Review: Dronedarone, a modified analogue of amiodarone, has the pharmacological ability of blocking multiple ion channels. This overview summarizes the pharmacokinetic and pharmacodynamic properties of dronedarone, evaluates its potential application to daily clinical cardiology practice according to the evidence provided by clinical trials, and provides a future clinical perspective for the use of this drug., What the Reader Will Gain: The readers will gain an understanding of the findings of recent trials performed with dronedarone, which will provide important information for this relatively new antiarrhythmic drug, used for the treatment of atrial fibrillation., Take Home Message: Dronedarone provides a reasonable efficacy and safety profile. Recent clinical trials indicate that dronedarone may support maintenance of sinus rhythm, decrease hospitalizations and reduce healthcare costs even in AF patients with structural heart disease but without severe or unstable cardiac failure.

Inflammation plays a key role in the pathogenesis of atherosclerosis. The more we discover about the molecular pathways involved in atherosclerosis, the more we perceive the importance of monocytes in this process. Circulating monocytes are components of innate immunity, and many pro-inflammatory cytokines and adhesion molecules facilitate their adhesion and migration to the vascular endothelial wall. In addition to the accumulation of lipids and formation of atherogenic 'foam' cells, monocytes may promote atherosclerotic plaque growth by production of inflammatory cytokines, matrix metalloproteinases, and reactive oxidative species. However, the contribution of monocytes to atherogenesis is not only limited to tissue destruction. Monocyte subsets are also involved in intraplaque angiogenesis and tissue reparative processes. The aim of this overview is to discuss the mechanisms of monocyte activation, the pivotal role and importance of activated monocytes in atherosclerotic coronary artery disease, their implication in the development of acute coronary events, and their potential in cardiovascular reparative processes such angiogenesis.

Genetic polymorphisms may affect platelets' responses to the antiplatelet therapy. Our aim was to determine the role of genetic polymorphisms on aspirin resistance in patients with coronary heart disease (CHD). A total of 126 consecutive patients (35-85 years old, 32% women) with chronic stable CHD was enrolled in the study. Platelet function assays were realized by the platelet function analyzer (PFA)-100 with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (Col/ADP) cartridges. Aspirin resistance was defined as having a closure time of less than 186 s with Col/Epi cartridges despite regular aspirin therapy. Factor V, prothrombin, factor XIII, beta-fibrinogen, plasminogen activator inhibitor I (PAI-1), glycoprotein IIIa, methylene tetrahydrofolate reductase, ACE and ApoB gene polymorphisms were determined by three consecutive steps: isolation and amplification of DNA and reverse hybridization. We determined that 30 patients (23.8%) had aspirin resistance by the PFA-100. Mean closure time measured with the Col/ADP cartridges was 74 +/- 12 s (51-104 s). Ten of the 30 patients with aspirin resistance were women (33.3%). Genetic polymorphisms were determined in 30 aspirin-resistant and 17 aspirin-sensitive patients. No statistically significant relationship was determined between aspirin resistance and the genetic panel. In our study we did not determine a significant relationship between the aspirin resistance and factor V, prothrombin, factor XIII, beta-fibrinogen, PAI-1, glycoprotein IIIa, methylene tetrahydrofolate reductase, ACE and ApoB gene polymorphisms.

Interleukin-15 (IL-15) is a potent proinflammatory cytokine that is now considered a key component of atherosclerosis. Proinflammatory gene polymorphisms lead to variations in the production and level of the proteins. In light of these findings, we hypothesized that variations in the gene coding for IL-15 influence the risk of coronary heart disease (CHD) by modulating the IL-15 levels. To test this hypothesis, we examined 5 single nucleotide polymorphisms (SNPs) in IL-15 gene and IL-15 levels in 102 patients with acute coronary syndrome (ACS), 102 patients with chronic ischemic stable CHD and 162 healthy control subjects. This study is the first report showing the influences of IL-15 gene variants and IL-15 levels on CHD. The five single nucleotide polymorphisms (SNPs) within the IL-15 gene, G367A, C267T, A14035T, C13687A, and A10504G were carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Serum IL-15 levels were significantly higher in both acute and chronic patients than in controls. Genetic variants of IL-15 gene and IL-15 levels were associated with CHD. In conclusion, our study supports the hypothesis that genetic variation in IL-15 gene and IL-15 levels influence the risk of CHD. Further studies are needed to confirm our hypothesis., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD)., Methods: The study included 235 patients with CAD and 268 healthy control subjects., Results: LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively., Conclusion: Genetic variants of PON1 55/192 and MTHFR were associated with CAD.

Background: Current evidence supports the preventive role of statins on platelet aggregation in patients with coronary heart disease., Aim: Our aim was to determine the effects of aggressive statin therapy on platelet function in patients with coronary heart disease., Material and Methods: A total of 178 consecutive patients (37-68 years old, 35.9% women) with stable coronary artery disease (CAD) was enrolled in the study. Platelet function assays were realized by the Platelet Function Analyzer (PFA)-100 with collagen and epinephrine (Col/Epi) and collagen and ADP (Col/ADP) cartridges. Aspirin resistance was defined as having a closure time (CT) of <186 s with Col/Epi cartridges despite regular aspirin therapy. A statin therapy protocol applied to the patients with aspirin resistance for 3 months., Results: We determined that 20 (11.2%) of patients had aspirin resistance by the PFA-100. Mean closure time measured with the Col/ADP cartridges was 83 +/- 18 s (53-162 s). Of the patients 12 were not on a statin therapy and eight were taking 10 mg daily atorvastatin. After 3 months of 40 mg daily atorvastatin therapy 13 subjects with aspirin resistance became aspirin sensitive by PFA-100 (P < 0.0001). There was also a significant decrease in total and LDL cholesterol levels and an increase in HDL cholesterol at the third month of statin therapy (P < 0.0001 for all)., Conclusion: Statin therapy reduced the in vitro aspirin resistance in 65% of the patients after a therapy of 3 months. Further studies are needed to elucidate the mechanism of statins' effects on platelet reactivity.

Background: P-wave dispersion (Pd), corrected P-wave dispersion (Pdc), QT-wave dispersion (QTd), and corrected QT-wave dispersion (QTdc) parameters were not assessed in Turner Syndrome (TS) before. The aim of this study is to investigate the cardiac arrhythmogenic potential in patients with TS., Methods: Thirty-one patients with TS and 30 healthy women were enrolled in the study. For this purpose 12-lead electrocardiogram (ECG) and 24-hour ambulatory ECG recordings were performed., Results: Pd, Pdc, QTd, and QTdc were significantly higher in patients with TS. On 24-hour ambulatory ECG recording, the mean heart rate (HR) was higher, while the mean of all RR intervals between normal beats (MeanNN), the standard deviation of all the RR intervals (SDNN), the square root of the mean of the squared differences of two consecutive RR intervals (rMSSD), and the percentage of the beats with consecutive RR interval difference more than 50 milliseconds (pNN50) were lower in TS., Conclusion: There were significant increases in Pd, Pdc, QTd, and QTdc in patients with TS and they may be features of the disease. The frequency of supraventricular arrhythmias was increased. There also was a significant deterioration of sympathetic and parasympathetic components of autonomic function as assessed by heart rate variability (HRV) in Turner patients.

Background: In the present study, nitric oxide (NO) was investigated to see if it mediated effects of nebivolol on apoptosis in the rat myocardial infarction (MI) model., Methods and Results: Rats were divided into 3 groups: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). The initial dose of nebivolol was administrated intravenously (iv) within 10 min of post-MI reperfusion and continued orally for 28 days. NO mediated effects of nebivolol were assessed either in the early (2(nd) day) or sub-acute (28(th) day) period of MI by histologic, hemodynamic and biologic studies. Left ventricular (LV) pressure changes were prevented with nebivolol (the increase in LV end-diastolic pressure and the decrease in maximum rise and fall rate of LV pressure (+dp/dt and -dp/dt) was significantly less in MI-nebivolol). Total and regional apoptotic indexes were significantly lower in the MI-nebivolol group (10.2 vs 7.1%, respectively on the 2(nd) day; p=0.004). Although plasma nitrite/nitrate, cyclic guanylate cyclase and peroxynitrite concentrations were high both in MI-control and MI-nebivolol groups on the 2(nd) day, these concentrations were decreased to the basal value on the 28(th) day in the MI-nebivolol group., Conclusion: As a result, nebivolol treatment (initially by iv within 10 min of reperfusion and continued orally) reduced the myocardial apoptosis after MI. This beneficial effect of nebivolol is mediated by NO regulation.

Background: Current evidence supports the central role of inflammation in all phases of the atherosclerotic process, including its thrombotic complications. Increased serum sCD40L may trigger platelet activation, so the aim of the present study was to determine the relation between sCD40L levels and aspirin-resistant platelet aggregation in patients with coronary atherosclerosis., Methods and Results: A total of 167 consecutive patients (39-85 years old, 35.9% women) with stable coronary artery disease was enrolled in the study. Platelet function was evaluated by a Platelet Function Analyzer 100 device (PFA-100) with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (ADP) (Col/ADP) cartridges. Aspirin resistance was defined as a closure time (CT) <186 s with Col/Epi cartridges, despite regular aspirin therapy. Serum sCD40L level was determined quantitatively with an ELISA method. Fifty-seven (34.1%) patients had aspirin resistance according to the PFA-100. Mean CT measured with the Col/ADP cartridges was 83+/-18 s (65-101 s). Mean serum sCD40L was 157 pg/ml (6-700 pg/ml) in the entire cohort. Patients with aspirin resistance had a mean serum sCD40L level of 166 pg/ml and patients with aspirin-sensitive platelet aggregation had an sCD40L level of 152 pg/ml (p=0.582)., Conclusion: The sCD40L level is similar in patients with aspirin-resistant and aspirin-sensitive platelet aggregation according to the PFA-100. There is still need for further studies to elucidate the relationship between aspirin-resistant platelet aggregation and sCD40L, which is now known to be prothrombotic, proinflammatory and to be a risk factor for cardiovascular events.

Background/aims: Overt and subclinical hypothyroidism are reported to be associated with increased cardiovascular disease risk. We have used coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) to determine coronary microvascular function in Hashimoto's thyroiditis patients with overt and subclinical hypothyroidism and to evaluate effects of L-thyroxine replacement on coronary endothelial function., Methods: In total, 10 overt hypothyroid patients, 10 subclinical hypothyroid patients, and 10 controls were enrolled. FT4, TSH, anti-thyroid antibodies, lipid profile, insulin, glucose, HOMA-IR, physical parameters, and CFR measured by TTDE were recorded before and after 6 months of L: -thyroxine replacement in all groups., Results: CFR values of all hypothyroid patients at baseline were significantly lower than those in controls. After L: -thyroxine, CFR increased significantly in overt and subclinical hypothyroidism with respect to the baseline measurements (P < 0.05). When baseline and second measurements were evaluated collectively for patients and controls, CFR was positively correlated with FT4 levels (r = 0.31, P = 0.01) and negatively correlated with TSH and HOMA-IR (r = -0.38, P = 0.002 and r = -0.42, P < 0.001, respectively)., Conclusion: Subclinical as well as overt hypothyroid patients have impaired coronary microvascular function which improved after L: -thyroxine therapy. Treatment of Hashimoto's thyroiditis patients with subclinical hypothyroidism should be considered to improve cardiovascular disease risk.

Aspirin resistance could be defined as thrombotic and embolic cardiovascular events despite regular aspirin therapy. The study aimed to determine the profile and prevalence of aspirin resistance in coronary artery disease patients. We evaluated the prevalence of aspirin resistance in a cohort of 505 patients with the diagnosis of coronary artery disease taking 80-300 mg regular aspirin daily. Platelet functions were analyzed by the Platelet Function Analyzer (PFA)-100 with collagen and epinephrine cartridges and collagen and ADP cartridges. A closure time of 186 s or less with the collagen and epinephrine cartridge was defined as aspirin resistance. Of the patients, 118 (23.4%) were aspirin resistant by the PFA-100. Aspirin-resistant patients were more likely to be older than aspirin-sensitive patients (P = 0.024). No statistically significant differences between the aspirin-resistant and aspirin-sensitive individuals were present in gender, major risk factors of coronary artery disease, number and localization of involved coronary vessels, serum lipid levels, and blood counts. According to the high prevalence of coronary heart disease, many people are affected by aspirin resistance, which may play a role in adverse cardiovascular events. Monitoring of platelet function in patients with coronary heart disease may support the optimization of antiplatelet therapy with additional and/or alternative agents.

Aspirin (acetylsalicylic acid) is one of the main therapeutics in prevention of thrombo-embolic vascular events. Its efficiency is proved in the prevention of cardiovascular events. However, antiplatelet effect of aspirin is not absolute in all patients and some patients experience thrombo-embolic events despite aspirin. These patients are clinically called as aspirin resistant or aspirin non-responders. Globally, a lot of people are affected by aspirin resistance according to the high prevalence of athero-thrombotic vascular diseases. A prevalence of 5.5-45% in patients with various cardiovascular disease by different laboratory methods has been reported for aspirin resistance. Clinical outcome of aspirin resistance has been demonstrated in patients with different vascular diseases. Detection of platelet function in patients treated with aspirin may be necessary in the prediction of clinical outcome. Point of care methods, which have correlated results with the standard light transmittance aggregometry may be appropriate choices in the detection of platelets' response to antiplatelet therapy. Adequate additional therapies may reduce atherothrombotic risks and major cardiovascular events rate in aspirin resistant subjects. None of the current researches advised the cessation of aspirin therapy. There is need to investigate the efficacy of additional adenosine diphosphate receptor antagonists or newer antiplatelet agents in aspirin resistant subjects. The intent of this paper is to review the literature discussing possible mechanisms, determination techniques, and clinical effects of aspirin resistance.

Objective: Relationship between adult growth hormone deficiency (AGHD) and increased cardiovascular disease risk is very well known in hypopituitary patients treated with conventional hormone replacement therapy other than growth hormone (GH) administration. Endothelial dysfunction, an early and reversible event in pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening and intima-media thickness (IMT). Coronary flow reserve (CFR) measurement by transthoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in AGHD., Design: Cross-sectional observational study., Patients: A total of 10 GH-deficient adults on conventional replacement therapy other than GH (4 males, 6 females; mean age 37 +/- 11 years) and 15 healthy subjects (7 males, 8 females; mean age 41 +/- 11 years) were studied. Patients and controls were all nonsmokers, normotensive and nondiabetic., Measurements: IGF-1, free T4, lipid profile, insulin, glucose, insulin resistance (IR), anthropometrical and physical parameters were recorded. CFR recordings and IMT measurements were performed using the Vivid 7 echocardiography device., Results: IMT were significantly higher in patients than controls (0.70 + 0.19 mm and 0.53 + 0.13 mm, respectively; P = 0.02). CFR was significantly lower in patients than in controls (1.96 +/- 0.35 and 2.62 +/- 0.45, respectively; P < 0.001). CFR was positively correlated with IGF-1 levels (r = 0.54, P = 0.005)., Conclusion: CFR is significantly lower in adults with GH deficiency than in controls. Direct correlation between CFR and IGF-1 concentrations suggests GH replacement could improve microvascular function and thereby could decrease cardiovascular morbidity and mortality in AGHD.

Aspirin resistance may increase the risk of major adverse cardiac events (MACE) more than threefold in patients with stable coronary artery disease (CAD). This study aimed to determine the prevalence of aspirin resistance in patients with stable CAD, the role of aspirin resistance on outcome in the follow-up, and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals. We detected the prevalence of aspirin resistance in 234 patients with stable CAD. Platelet function was determined by PFA-100 with collagen and/or epinephrine and collagen and/or ADP cartridges. The mean follow-up time was 20.6 +/- 6.9 months. The primary endpoints of the study were occurrence of myocardial infarction, unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. During follow-up, MACE occurred in eight patients (15.4%) with aspirin resistance and in 20 patients (11.0%) with aspirin-sensitive platelet aggregation (P = 0.269). MACE increased in aspirin-resistant patients after termination of clopidogrel therapy. Eleven patients experienced MACE after cessation of clopidogrel therapy (P < 0.001). The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100. The MACE prevalence increased during follow-up, however, just after cessation of clopidogrel therapy.

Background: Impaired heart rate recovery (HRR) is a powerful predictor of overall mortality., Aim: The aim of the present study is to assess HRR in young adult males with metabolic syndrome and to compare HRR with those of obese patients who do not meet the criteria for metabolic syndrome., Patients and Methods: Sixty-four newly diagnosed and untreated young male subjects (24 +/- 3 years) with metabolic syndrome and 40 age and sex matched obese or overweight control subjects (ages 23 +/- 3 years) were enrolled in the study. All subjects performed a symptom limited exercise stress test under the standard Bruce protocol. HRR was calculated in the first, second and third minutes of the recovery period. The relationship between metabolic syndrome and HRR was evaluated via logistic regression analysis and a P-value < 0.05 was accepted as significant., Results: Body mass index (BMI) was 38.6 +/- 3.68 and 32.22 +/- 2.99 kg/m(2) in the study and control groups, respectively (P < 0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, systolic and diastolic blood pressures and fasting glucose levels were significantly higher in the study group. HRR in the first minute of the recovery period and mean exercise capacity were significantly lower in the study-group patients with metabolic syndrome (P < 0.001 and P = 0.012, respectively)., Conclusion: We determined that HRR was impaired in young adult males with metabolic syndrome compared with obese ones who do not meet the criteria of metabolic syndrome. This decreased HRR may have prognostic value in the prediction of vascular events in patients with metabolic syndrome.

Background: Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events (MACE) in patients with stable coronary artery disease., Aim: The aim of our study was to determine; the prevalence of aspirin resistance in patients with acute coronary syndromes, the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects., Material and Methods: We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were myocardial infarction, unstable angina, cardiac death., Results: 19% (n = 20) of patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9 patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that aspirin resistance was an independant predictor of MACE. The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months (p = 0.040)., Conclusions: We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance, was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation. Our results showed that aspirin resistance, was an independant predictor of MACE in patients with acute coronary syndrome.

Endothelial dysfunction is an early key event in the development of atherosclerotic cardiovascular disease observed in chronic renal failure patients. The role of renal transplantation (RTx) on endothelial dysfunction is still unclear. The aim of this study was to evaluate the endothelial function of chronic renal failure patients before RTx (while they were on hemodialysis, HD), and after RTx (at the 6th and 12th months) by a noninvasive method, brachial arterial ultrasound. A total of 22 (17 male, mean age: 33.9 +/- 11.6 years) RTx recipients were enrolled in the study. Endothelium-dependent vasodilation (EDD) was assessed by establishing reactive hyperemia. EDD prior to transplantation was significantly lower when compared with EDD measured at the 6th and 12th months after RTx (EDD pretransplantation: 6 +/- 3.7%, EDD at the 6th month of RTx: 8.3 +/- 2.3% and EDD at the 12th month of RTx: 12.1 +/- 3.6%, P < 0.001). When the EDD values measured at the 6th and 12th months of RTx were compared, measurements of the 12th month were found significantly higher than those of the 6th month (P < 0.001). Our results also showed that RTx has provided improvement in endothelial function by eliminating the uremic environment although not in the early post-RTx period.

Background: Obstructive sleep apnea syndrome (OSAS) influences endothelial function and causes hypertension., Objectives: Our aim was to evaluate the role of endothelial dysfunction in the pathogenesis of hypertension in OSAS., Methods: Twenty-three patients with OSAS but without hypertension and 15 healthy normotensive subjects were investigated. The presence or absence of OSAS was evaluated with a sleep study. Endothelial function was investigated with brachial artery ultrasound examination., Results: Baseline characteristics were equivalent between the two groups. Minimal oxygen saturation and apnea-hypopnea indexes in the OSAS and control groups were 62.9 +/- 16.5 versus 94.9 +/- 1.1% (p < 0.0001) and 53.1 +/- 20.3 versus 3.8 +/- 0.9 (p < 0.0001), respectively. There was not statistically significant difference between basal brachial artery diameters measured in the morning and in the evening in all groups. Flow-mediated dilation (FMD) values measured in the morning were lower than those measured in the evening in both OSAS patients and the control group: FMD of OSAS patients was 6.04 +/- 3.18% in the morning and 10.38 +/- 4.23% in the evening hours (p = 0.001), and FMD of control subjects was 10.9 +/- 2.6% in the morning and 13.9 +/- 2.32 in the evening hours (p = 0.002). Differences in FMD values measured both in the morning and evening hours in OSAS patients were lower compared with those in control subjects (p < 0.0001 in the morning hours and p = 0.003 in the evening hours)., Conclusions: We detected a prominent diurnal deterioration in endothelial function in normotensive OSAS patients compared with healthy subjects. This deterioration may occur due to ongoing hypoxemia during the night and it may be a possible cause of hypertension and atherosclerotic cardiovascular diseases in patients with OSAS.

Background: Left ventricular diastolic dysfunction has been shown in patients with autosomal-dominant polycystic kidney disease (ADPKD). However, there is no study evaluating right ventricular functions in these patients., Methods: In the present study, diastolic functions of both ventricles in normotensive and hypertensive ADPKD patients with well-preserved renal function were investigated. Fifteen hypertensive and 16 normotensive patients with ADPKD with well-preserved renal function, 16 patients with essential hypertension, and 24 healthy subjects were included in the study. Conventional left and right ventricular echocardiographic measurements were performed in all subjects. Left and right ventricular functions were investigated both by myocardial performance index (MPI) [calculated by dividing the sum of isovolumic contraction time and isovolumic relaxation time (IVRT) by ejection time] and by tissue Doppler imaging (TDI)., Results: Left ventricular deceleration time and IVRT were significantly prolonged in hypertensive patients with ADPKD compared with patients with essential hypertension and even in normotensive patients with ADPKD compared with healthy subjects. Left and right MPIs were significantly higher in patients with ADPKD compared with healthy subjects, showing systolic and diastolic dysfunction. Moreover, by using TDI, the peak early diastolic mitral annular velocity (Em) to peak late diastolic mitral annular velocity (Am) ratio and the peak early diastolic tricuspid annular velocity (Et) to peak late diastolic tricuspid annular velocity (At) ratio were decreased in patients with ADPKD, suggesting biventricular diastolic dysfunction., Conclusion: Both hypertensive and normotensive patients with ADPKD show significant biventricular diastolic dysfunction, suggesting cardiac involvement very early in the course of ADPKD.

Objectives: The aim of our study was to determine the relation between exercise stress test and aspirin resistance in patients with stable coronary artery disease., Background: Clinically aspirin resistance is defined as having thrombotic and embolic cardiovascular events despite regular aspirin therapy., Methods: We studied platelet functions of 62 patients with stable coronary artery disease and 20 subjects with normal coronary arteries by Platelet Function Analyzer (PFA-100, Dade Behring, Germany) at rest and after exertion with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP cartridges. Closure time (CT)<186 seconds was defined as aspirin resistance with Col/Epi cartridges of PFA-100. Symptom limited treadmill stress test (protocol of Bruce) was performed with Oxford Streslink TD-1 system., Results: 8 (12.9%) patients were aspirin resistant by PFA-100 (CT<186s despite regular aspirin therapy) at rest. At the first minute of the recovery period of exercise stress test 14 (22.5%) patients were aspirin resistant by PFA-100. CTs with Col/ADP were respectively 89+/-6 s (83--100s) and 89+/-5 s (82--104s) at rest and after exercise (p=0.107). 20.3% (11/54) of patients known as in vitro aspirin sensitives at rest had shorter CTs and 11.1% (6/54) had aspirin resistance after exercise (p=0.004). There was no statistically significiant difference in platelet functions in the control group after exertion., Conclusion: We conclude that 11.1% of in vitro aspirin sensitive subjects at rest had aspirin resistance after exercise by PFA-100. In some individuals, exercise induced platelet activation is aspirin insensitive at usual antiplatelet doses. We need further clinical trials to optimize antiplatelet therapy in patients with coronary artery disease.

Objectives: The aim of our study was to determine the relation between platelet glycoprotein IIIa (Pl A ) polymorphism and aspirin resistance in patients with intracoronary stent restenosis., Background: Clinically, aspirin resistance is defined as having thrombotic and embolic cardiovascular events despite regular aspirin therapy. Platelet glycoprotein IIIa polymorphism is said to be a possible mechanism of aspirin resistance., Methods: We studied the prevalence of aspirin resistance in 204 previously intracoronary stent-implanted patients with stable coronary artery disease. In 102 of these patients, intracoronary stent restenosis was present. Platelet functions were analyzed in a platelet function analyzer (PFA-100, Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or adenosine diphosphate cartridges. Closure time <186 seconds was defined as aspirin resistance with Col/Epi cartridges of PFA-100. The Pl A polymorphisms of 43 aspirin-resistant and 51 aspirin-sensitive subjects were determined with polymerase chain reaction and restriction fragments length polymorphism., Results: A total of 31.3% (n = 32) of patients with intracoronary stent restenosis and 10.7% (n = 11) of patients with patent intracoronary stents were resistant to aspirin by PFA-100. The Pl A1,A1 allele of glycoprotein IIIa was present in 36 subjects (83.7.%) and the Pl A1,A2 allele was present in 7 subjects (16.2.%) in the aspirin-resistant patients group. The Pl A1,A1 allele of glycoprotein IIIa was present in 37 subjects (72.5%) and the Pl A1,A2 allele was present in 14 subjects (27.5%) in the aspirin-sensitive patients group ( P = .195)., Conclusion: Our results suggest that platelets of patients with intracoronary stent restenosis with or without Pl A2 heterozygosity of glycoprotein IIIa are more likely to be resistant to low-dose aspirin therapy.

Impaired endothelium-dependent vasomotion is a diffuse disease process resulting in abnormal regulation of blood vessel tone and loss of several atheroprotective effects of the normal endothelium. The aim of the present study was to investigate the effects of aging and hypertension on endothelial function. Sixty-six geriatric subjects with ages over 60 (48 hypertensive and 18 healthy) and 40 middle-aged subjects (16 hypertensive and 24 healthy) were included in the study. Systemic vascular endothelial function was evaluated through measuring brachial arterial vasodilation, a physiologic answer to reactive hyperemia occured with increased blood flow in the vessel after transient ischemia (flow-mediated dilation, FMD%), and with carotid artery intima-media thickness (IMT) measurement, using high-resolution ultrasonography. Endothelial independent vasodilation was also measured after administration of sublingual isosorbide dinitrate (isosorbide dinitrate mediated dilation, IDNMD%). FMD% was significantly decreased in elderly and/or hypertensive (HT) patients (geriatric HT: 9.5 +/- 4.7%, geriatric non-HT: 12.7 +/- 5.5%, middle-aged HT: 12.9 +/- 4.3% and middle-aged non-HT: 18.9 +/- 8.1%) (geriatric HT versus geriatric non-HT (P = 0.02), geriatric HT versus middle-aged HT (P = 0.01), geriatric non-HT versus middle-aged non-HT (P = 0.008)). Both FMD% and IDNMD% were inversely correlated with age, baseline vessel diameter and carotid artery intima-media thickness. FMD% was also inversely correlated with diastolic blood pressure. No correlation was found between FMD% and systolic blood pressure, serum cholesterol and triglyceride levels. Endothelium dependent (EDD) and independent dilatation of large arteries decreased with aging even in the healthy elderly, and FMD further declined in HT elderly patients, indicating that age and hypertension independently impair endothelial function. Positive correlations with age and hypertension, and significant inverse correlation with FMD, makes carotid artery IMT a possible indicator of endothelial function.

An adolescent female who presented amelogenesis imperfecta with severe anterior open bite, long face, facial asymmetry, high angle, and Class III skeletal pattern was treated with an interdisciplinary (orthodontics, orthognathic surgery, and prosthodontics) treatment approach. Presurgical orthodontic treatment was followed by surgical maxillary posterior impaction with anterior advancement and mandibular setback operation with vertical chin reduction and genioplasty. After the surgery, anterior ceramic laminate veneers and posterior full ceramic onlay-crowns were performed. The results showed that function and esthetics were achieved successfully with interdisciplinary collaboration.