Seyit Ahmet Ay

The Comparative Effects of Valsartan and Amlodipine on vWf Levels and N/L Ratio in Patients with Newly Diagnosed Hypertension

High levels of circulating Von Willebrand factor (vWf) and increased neutrophil to lymphocyte (N/L) ratio may reflect vascular inflammation in hypertensive patients. In present study, we aimed to investigate the effects of valsartan as an angiotensin II receptor antagonist and amlodipine as a calcium channel blocker on the vWf levels and N/L ratio in patients with essential hypertension. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5–10 mg/day) as group A (n = 20 mean age = 51.85 ± 11.32 y) and angiotensine II receptor blocker (valsartan, 80–320 mg/day) as group B (n = 26 mean age = 49.12 ± 14.12 y). Endothelial dysfunction and vascular inflammation were evaluated with vWf levels and N/L ratio in hypertensive patients before treatment and after treatment in the 12th week. No statistically significant differences were found among the groups in terms of age, sex, and body mass index (BMI). There was a significant decrease in vWf levels (P < .001) and N/L ratio after treatment (P = .04, P < .001, respectively) in both the groups. Von Willebrand factor levels and N/L ratio are very important markers having a role in vascular inflammation and antihypertensive treatment with amlodipine and valsartan may improve cardiovascular outcomes by decreasing these biomarkers.

Low Triiodothyronine Alters Flow-Mediated Vasodilatation in Advanced Nondiabetic Kidney Disease

Background/Aims: Subclinical or frank hypothyroidism is causally implicated in endothelial dysfunction. Since the plasma concentration of the active form of thyroid hormone, triiodothyronine (T3), is reduced in chronic kidney disease (CKD), where endothelial function is frequently altered, low T3 may be a factor implicated in this disturbance in CKD patients. Methods: We investigated the relationship between flow-mediated vasodilatation (FMD) and thyroid hormones in a series of 217 nondiabetic patients with stage 3–4 CKD. Results: The plasma concentration of free T3 (fT3) was closely associated with FMD (r = 0.38; p < 0.001). fT3 was also inversely associated with hemoglobin (r = –0.41; p < 0.001), systolic pressure (r = –0.28; p < 0.001) and the plasma concentration of the endogenous inhibitor of NO synthase, asymmetric dimethylarginine (ADMA; r = –0.18; p = 0.007). However, adjustment for ADMA markedly attenuated the fT3-FMD link, a phenomenon suggesting that raised plasma ADMA, possibly driven by low fT3, at least in part mediates the adverse effects of low T3 on endothelial function in CKD. Conclusions: Low T3 in patients with moderate-to-severe CKD is a marker of endothelial dysfunction. This study sets a solid rationale for designing specific intervention studies aimed at clarifying the nature (causal or not causal) of the endothelial function-T3 link in CKD.

Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: comparative effects of amlodipine and valsartan

Abstract Vascular inflammation plays an important role in the pathophysiology of hypertension and high levels of endocan may reflect ongoing vascular inflammation in hypertensive patients. In the present hypothesis-generating study, we aimed at investigating the comparative effects of amlodipine and valsartan on endocan levels in newly diagnosed hypertensive patients. The study population consisted of 37 untreated hypertensive patients who were randomized to the two treatment arms. After baseline assessment, each patient was randomly allocated to either 10 mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3 males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP) and serum endocan were measured before and every 2 weeks during drug treatment. There was no statistically significant difference between the two treatment arms as far as baseline socio-demographic and clinical characteristics are concerned. After a 3-month treatment period, systolic and diastolic BP values significantly reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels were significantly decreased in both treatment arms (p < 0.05). However, amlodipine caused a greater percent decrease in circulating endocan levels compared with valsartan at the end of the treatment period. Both drugs reduced high sensitivity C-reactive protein values. However, the statistical significant difference vs baseline was achieved only in the group treated with amlodipine. No correlation was found between endocan plasma levels and BP reduction. The results of this hypothesis-generating study suggest that amlodipine and valsartan decrease endocan levels in newly diagnosed hypertensive patients. The effects, which are more evident with amlodipine, may contribute to the anti-inflammatory effects exerted by the two drugs on the vascular target.

The Relationship Between Some of the Cardiovascular Risk Factors and Arterial Stiffness Parameters in Essentially Hypertensive Patients

Hypertensive patients have strong evidence of endothelial dysfunction. We aimed to explore the relationships between cardiovascular risk factors and arterial stiffness parameters in hypertensive patients. The study population included 109 hypertensive patients (63 females, 46 males). Arterial stiffness measures including pulse wave velocity, augmentation index, and central aortic pressure were applied. Augmentation index and central aortic pressure were found to be significantly higher (P < .001 and P = .03, respectively) in women. The higher augmentation index and central aortic pressure values were observed in women than in men. These data offer new evidences for the role of sex hormones in the pathogenesis of atherosclerosis in women.

The Comparative Effects of Valsartan and Amlodipine on Vascular Microinflammation in Newly Diagnosed Hypertensive Patients

Pentraxin 3 (PTX3) is a new candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors. We aimed to investigate the effects of valsartan and amlodipine on the PTX3 and C-reactive protein (CRP) levels in patients with essential hypertension. Patients with a newly diagnosed essential hypertension were admitted to our internal medicine outpatient clinic. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5–10 mg/day) as group A (n = 22; mean age ± standard deviation [SD]: 52 ± 11 year) and angiotensine II receptor blocker (valsartan, 80–320 mg/day) as group B (n = 28; mean age ± SD: 50 ± 14 year). Endothelial dysfunction and systemic inflammation were evaluated with PTX3 and CRP. There was a significant decrease in the level of PTX3 after treatment in two groups (P < .05). Although there was a significant decrease in the level of CRP after treatment in amlodipine group, there was no significant decrease in the levels of PTX3 and CRP after treatment in two groups. There were no significant differences in the systolic and diastolic blood pressure reduction between the two treatment groups. In the treatment of hypertension, prior knowledge of the level of plasma PTX3 could be important in antihypertensive drug choice. C-reactive protein and PTX3 are the markers that have role in vascular inflammation and are found associated with the prognosis of cardiovascular outcomes in many trials. In our study, PTX and CRP levels were decreased when compared to baseline levels.

Asymmetric Dimethylarginine and Augmentation Index in Newly Diagnosed Patients With Hypertension

Pulse wave velocity (PWV), augmentation index (Aix), and central aortic pressure (CAP) are arterial stiffness markers of endothelial dysfunction (ED). We investigated the relationship between arterial stiffness parameters and asymmetric dimethylarginine (ADMA; a marker of ED), in newly diagnosed patients with hypertension (n = 101; 61 females). These patients were investigated in accordance with the recommendations of hypertension guidelines. Arterial stiffness was measured, and serum ADMA and C-reactive protein (CRP; a marker of inflammation) levels were determined. In both women and men, there was no difference in terms of age, body mass index, systolic and diastolic blood pressures, PWV, CAP and the levels of ADMA, while Aix and CRP levels were significantly higher in women (P = .004, P = .046, respectively). In the whole group, ADMA levels correlated with Aix (Pearson r = .237, P = .024). Our findings provide further evidence of a link between arterial stiffness and ED in newly diagnosed patients with hypertension.

Investigation of the Aortic Pulse Wave Velocity in Patients with Gilbert’s Syndrome

Arterial stiffness is currently the “gold standard” measure of aortic (carotid-femoral) pulse wave velocity (PWV), which is an important independent predictor of risk of developing a cardiovascular event. Gilbert’s syndrome is a congenital disorder characterized by intermittent and non-hemolytic elevation of indirect bilirubin levels due to the deficiency of the enzyme UDP-glucuronyl transferase in the liver and many prospective studies found an inverse relationship between bilirubin levels and cardiovascular events in these patients. We aimed to investigate serum bilirubin levels and arterial stiffness parameters in patients with Gilbert’s syndrome in this study. A total of 53 cases, consisting of 26 patients with a diagnosis of Gilbert’s syndrome and 27 healthy control subjects, were included in the study. Serum bilirubin levels, other routine blood chemistry, and arterial stiffness measurements were recorded. The mean ages of Gilbert’s syndrome and the control group were 31.5 ± 9.7 and 36.8 ± 11.1 years, respectively. PWV measurements were significantly lower in Gilbert syndrome patients (6.68 and 7.3 m/s in patients and controls; respectively) (P < .05). In correlation analysis in Gilbert’s syndrome patients, PWV had a significant correlation with total and indirect bilirubin levels (r = −0.370, P = .009/r = −0.495, P = .003, respectively). Gilbert’s syndrome patients have lower PWV measurements compared to healthy subjects, and the total and indirect bilirubin levels are also associated with PWV measurements. These findings may indicate the decreased atherosclerotic disease incidence in Gilbert’s syndrome patients.

Arterial stiffness and endothelial inflammation in prediabetes and newly diagnosed diabetes patients

OBJECTIVE There is a growing body of data supporting the association between diabetes and microcirculatory disfunction. We aimed to study e-selectin levels, and their associations with serum markers of inflammation and arterial stiffness in prediabetes and newly diagnosed diabetes patients in this study. SUBJECTS AND METHODS Sixty patients (25 females) with a newly established elevated fasting serum glucose [20 impaired fasting glucose (IFG), 20 impaired glucose tolerance (IGT), 20 newly diagnosed diabetes (T2DM)] and 17 healthy controls (13 females) were included in the study. Serum e-selectin and hs-CRP levels, and arterial stiffness parameters of the patients were studied. RESULTS Fasting serum glucose was the most important predictor of serum e-selectin levels. Pulse wave velocity and central aortic pressures were significantly higher in IFG, IGT and T2DM groups, compared to controls (p = 0.001, < 0.001, 0.013 and 0.015, 0.002, 0.009, respectively). The mean arterial pressure did not show any significant association with serum e-selectin and hs-CRP levels (β coefficient: 0.092, p = 0.358; and β coefficient: 0.189, p = 0.362, respectively). CONCLUSION Prediabetes patients have increasing e-selectin levels through the diagnosis of T2DM. E-selectin is associated with serum glucose levels. Prediabetic and newly diagnosed diabetics have higher arterial stiffness measurements. Serum e-selectin may be a good marker of endothelial inflammation and dysfunction increasing in parallel with serum glucose levels, predicting future cardiovascular events.

Nonalcoholic Fatty liver disease may be associated with coronary artery disease complexity.

We read the article ‘‘Association between nonalcoholic fatty liver disease and coronary artery disease complexity in patients with acute coronary syndrome: a pilot study’’ by Agaç et al. The authors assessed the relationship between nonalcoholic fatty liver disease (NAFLD) and SYNTAX score (SS) in patients who presented with acute coronary syndrome (ACS). They concluded that the presence of NAFLD is associated with higher SS in these patients. Serum alanine transaminase and aspartate transaminase activities are independently positively associated with the risk and severity of premature coronary artery disease (CAD), suggesting that these enzymes could serve as surrogate markers for cardiovascular (CV) risk in this specific group of patients. Serumg-glutamyltransferase activity is also an indicator of oxidative stress and is associated with CV disease. These associations can be partly attributed to NAFLD and insulin resistance, but there may be additional underlying mechanisms that contribute to the increased CV risk (eg, inflammation and oxidative stress). The NAFLD is a hepatic manifestation of metabolic syndrome (MetS). The MetS is a clinical entity comprising risk factors such as hypertension, glucose intolerance, atherogenic lipid profile, abdominal obesity, lack of physical activity, and increased inflammatory state. Most of the recent studies demonstrated that there was a correlation between the inflammatory mediators and the components of MetS. Elevated inflammatory mediators are a common indicator of atherosclerotic involvement of the vascular structure indicating CAD, cerebrovascular disease, peripheral arterial disease, and chronic inflammatory disease. Inflammatory mediators can also be affected by atherosclerotic risk factors such as smoking, alcohol consumption, hypercholesterolemia, and hypothyroidism. In this context, the authors did not mention some of the factors affecting these markers, including alcohol consumption, insulin resistance, hypercholesterolemia, hypothyroidism, heart failure, cerebrovascular disease, peripheral arterial disease, and chronic inflammatory disease in their study. Obstructive sleep apnoea syndrome (OSAS) and NAFLD are common conditions in clinical practice. Patients with OSAS should be screened for the presence and severity of NAFLD. It would be useful if the authors provided information about these factors. In a previous study, the presence of diabetes mellitus, lower values of high-density lipoprotein cholesterol, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate were independent predictors of CAD complexity. The SS was developed for the grading of coronary complexity based on angiographic visual assessment. The addition of clinical risk factors to the SS may further enhance its usefulness to objectively evaluate the patients. The Logistic Clinical SS consisting of 4 continuous variables (SS, age, creatinine clearance, and LVEF) substantially enhances the risk stratification of patients with CAD for the outcome of 1-year all-cause death compared with the SS alone. The Logistic Clinical SS was able to accurately distinguish patients with or without a clinical outcome and could accurately predict individual patient risk without underor overestimating the risk. Renal dysfunction included in this score may predict CAD and could estimate the risk of mortality and morbidity. Also, we believe that it would be useful to provide interobserver and intraobserver variability for CAD severity assessment in the Agaç et al study. In conclusion, NAFLD is associated with higher SS in patients who presented with ACS in the Agaç et al study. However, the reasons for higher SS are very complex, and the roles of the risk factors discussed above deserve further largescale prospective randomized clinical trials.

Cell-Free Circulating DNA as a Novel Biomarker in Patients with the Acute Coronary Syndrome

in many acute diseases as well as in some chronic conditions such as cancer and autoimmune diseases. It has been considered as a potential biomarker of aging, reflecting systemic inflammation and cell death nowadays. Cardiovascular complications are frequent in patients with obstructive sleep apnea and have been associated with morbidity and mortality in these patients [4] . Also, increases in serum concentrations of cf-DNA in these patients were positively correlated with disease severity. Serum cfDNA may become an important parameter for monitoring the severity of obstructive sleep apnea and response to therapy [5] . Furthermore, nonalcoholic fatty liver disease is an independent risk factor for CAD, and CAD is the most common cause of death in these patients. The presence of nonalcoholic fatty liver disease is linked to higher inflammatory parameters in nonhypertensive, nondiabetic individuals [6] . Thus, whether higher plasma DNA levels are the result of the acute coronary syndrome or of other comorbidities needs to be clarified to better prove its specificity. Hence, the inflammatory status can be affected by atherosclerotic risk factors such as hypertension, smoking, alcohol consumption, hypothyroidism and impaired glucose tolerance, and a higher inflammatory status, such as an inflammatory disease, by slow coronary flow [7] , cardiac syndrome X and infection [8] . Increased inflammation is a common indicator of atherosclerotic inWe have read the article by Cui et al. [1] with great interest. The authors aimed to investigate cell-free circulating DNA (cf-DNA) concentrations in patients with the acute coronary syndrome and the relationship of cf-DNA with clinical features. They concluded that cf-DNA may be a valuable marker for diagnosing and predicting the severity of coronary artery lesions and risk stratification in the acute coronary syndrome. Cardiovascular diseases (CAD) are the most important causes of mortality and morbidity in developed countries worldwide. Growing evidence suggests that inflammatory pathways influence the course of CAD, both with regard to the development of mild CAD but also outcome in patients with established severe CAD due to plaque destabilization and susceptibility to ischemia-driven myocardial damage. In the general population, high plasma levels of inflammatory markers have been found to increase the risk of coronary events, left ventricular function impairment and cardiovascular death [2] . cf-DNA has been demonstrated as a biomarker in many pathologies but it can also be found in small amounts in the plasma of healthy individuals. cf-DNA levels correlated with the levels of established markers of myocardial necrosis [3] . High cf-DNA levels have been associated with a poor prognosis in various diseases and cfDNA levels have been reported to increase Received: May 20, 2013 Accepted: May 23, 2013 Published online: August 17, 2013