Ozcan Orscelik

Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients.

Background/Aims: Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. Methods: Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. Results: Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. Conclusion: Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.

Bilirubin levels and the burden of coronary atherosclerosis in patients with STEMI.

We investigated whether serum bilirubin level (a marker of heme oxygenase activity) is a predictor of high levels of SYNTAX score (SXscore) in patients with acute myocardial infarction. Patients (n = 281; male 77%; mean age 60 ± 12) who were admitted with ST-elevation myocardial infarctions (STEMIs) were enrolled. Patients were divided into 2 groups. Group 1 was defined as SXscore <22 and group 2 was defined as SXscore ≥22. Total bilirubin levels were significantly higher in the high-SXscore group than in the low-SXscore group (0.86 ± 0.42 vs 1.02 ± 0.51, P = .005). A significant correlation was detected between total bilirubin and SXscore (r = .42; P = .001). At multivariate analysis, total bilirubin (odds ratio: 1.86, 95% confidence interval 1.04-3.35; P = .038) was an independent risk factor for high SXscore in patients with STEMI. In conclusion, serum bilirubin level is independently associated with SXscore in patients with STEMI.

High levels of serum uric acid predict severity of coronary artery disease in patients with acute coronary syndrome.

We aimed to elucidate the relation between serum uric acid (SUA) level and severity of coronary artery disease (CAD) in nondiabetic, nonhypertensive patients (n = 246) with acute coronary syndrome (ACS). Severity of CAD was assessed by the Gensini score. One, 2, and 3 or more diseased vessels were identified in 87 (35.4%), 55 (22.4%), and 104 (42.2%) patients, respectively. Patients with hyperuricemia had higher Gensini score, high number of diseased vessels, critical lesions, and total occlusion. Serum uric acid level was significantly associated with number of diseased vessels. Serum uric acid was an independent risk factor for multivessel disease by univariate analysis. High levels of SUA associated with the severity of CAD in nondiabetic, nonhypertensive patients with ACS.

A Link between the Intrarenal Renin Angiotensin System and Hypertension in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Early onset of hypertension and its consequences account for the great majority of deaths in patients with autosomal dominant polycystic kidney disease (ADPKD). Renin-angiotensin system (RAS) components have been shown in ADPKD kidneys independent of systemic RAS. Thus, we examined the urinary angiotensinogen (UAGT) levels as a biomarker of intrarenal RAS status in ADPKD patients with/without hypertension and healthy subjects. Methods: Eighty-four ADPKD patients (43 with hypertension and 41 without hypertension) and 40 healthy controls were studied cross-sectionally. Patients with glomerular filtration rate <60 ml/min were excluded from the study. Hypertension was diagnosed with ambulatory blood pressure monitoring. Urinary and plasma concentration of angiotensinogen, spot urine microprotein and creatinine (UCre) levels were recorded for each participant. Results: UAGT/UCre levels were higher in hypertensive ADPKD patients (23.7 ± 8.4) compared with normotensive ADPKD patients (16.6 ± 5.2) and healthy controls (6.9 ± 3.3; p < 0.001). In univariate analysis, UAGT correlated with systolic blood pressure, diastolic blood pressure (DBP) and proteinuria. The independence of these correlations was analyzed in a regression model, and UAGT was shown to be significantly predicted by proteinuria and DBP. Conclusion: Intrarenal RAS activation which is monitored by UAGT levels clinically may be a harbinger of hypertension and kidney disease in ADPKD patients.

Serum Uric Acid Levels and Endothelial Dysfunction in Patients with Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit endothelial dysfunction (ED) despite normal levels of renal function. Hyperuricemia occurs in these patients and has been postulated to affect ED through the generation of oxidative stress. We therefore investigated the prevalence of ED and its association with serum uric acid levels in early-stage ADPKD. Methods: A cross-sectional design was used for the assessment of prevalent patients with early-stage (normal renal function) ADPKD (n = 91) from two academic medical centers. ED was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Serum uric acid levels were evaluated using an Olympus AU2700 autoanalyzer. Results: ADPKD patients with higher serum uric acid levels had a higher asymmetric dimethylarginine (ADMA) level (1.19 ± 0.2 vs. 1.47 ± 0.3, p < 0.001) and lower FMD rates (8.1 ± 1.3 vs. 6.8 ± 0.7, p < 0.001). In multiple regression analysis for predictors of cohort FMD, uric acid (β = -0.32, p < 0.001), ADMA (β = -0.36, p < 0.001), high-sensitivity C reactive protein (CRP; β = -0.32, p < 0.001) and estimated glomerular filtration rate (eGFR; β = 0.33, p < 0.001) all predicted FMD. Conclusions: In early-stage ADPKD patients, uric acid levels, serum ADMA and eGFR all independently predict ED in a similar manner. Future studies are needed to investigate the causes of elevated serum uric acid, ADMA and CRP in these patients.

The Association Between Arterial Stiffness and Fluid Status in Peritoneal Dialysis Patients

♦ Objectives: In this study our aim was to evaluate the relationship between degree of fluid status and arterial stiffness measured by pulse wave velocity (PWV) in peritoneal dialysis (PD) patients. Fluid status was determined by different methods including fluid overload measured by bioimpedance (Body Composition Monitor, BCM), calf normalized resistivity (CNR), plasma N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and extracellular to intracellular water ratio (ECW/ICW). ♦ Methods: Sixty PD patients were evaluated. They were stratified into normo- and hypervolemic groups according to their fluid overload (FO). CNR was calculated from resistance at 5 kHz using calf bioimpedance spectroscopy. Arterial stiffness was assessed by PWV. Additionally, all patients underwent transthoracic echocardiography and had levels of NT-proBNP measured. ♦ Results: PWV was higher in the hypervolemic compared to normovolemic patients (9.99 ± 2.4 m/sec vs 7.48 ± 2.3 m/sec, p < 0.001). Hypervolemic patients had higher NT-proBNP levels (3065 ± 981 pg/mL vs 1095 ± 502 pg/mL, p < 0.001), a higher ratio of ECW/ICW; (0.93 ± 0.11 vs 0.81 ± 0.08, p < 0.001) and lower CNR (13.7 ± 2.4 vs 16.0 ± 3.3 W m3/kg*10-2, p = 0.005). NT-pro BNP level, ECW/ICW ratio, relative FO, and left ventricular (LV) mass index were positively and CNR negatively correlated with PWV. Relative FO and CNR independently predicted PWV in multivariate analysis adjusted for age, duration of PD, body mass index and mean arterial pressure. ♦ Conclusions: Arterial stiffness is increased in fluid-overloaded PD patients. Our results indicated that fluid status is an independent predictor of PWV.

Acute effects of intracoronary nitroglycerin and diltiazem in coronary slow flow phenomenon.

Background The coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder angiographically defined by delayed opacification of the distal vasculature in the absence of obstructive coronary artery disease. We aimed to investigate and compare the effects of intracoronary nitrate and diltiazem on thrombolysis in myocardial infarction frame count (TFC) in patients with CSFP during coronary angiography. Methods Sixty patients with CSFP were randomly divided into 2 groups. The first group is nitroglycerin group with 30 patients (22 men; mean [SD] age, 50 [12] years), and the second is diltiazem group with 30 patients (27 men; mean age, 54 ± 11 years); intracoronary 5-mg diltiazem or 250-μg nitroglycerin was administered. Heart rate, systolic and diastolic blood pressures, and TFCs in all 3 coronaries were recorded before and after administering these medications. Results After nitroglycerin administration, systolic and diastolic blood pressures decreased, heart rates significantly increased, and TFCs decreased in all coronaries (P < 0.001 for 3 coronaries). After the application of intracoronary 5-mg diltiazem, heart rate, systolic and diastolic blood pressures, and TFCs were found significantly lower than predrug values (P < 0.001 for all values). When the percent TFC reductions, after the application of intracoronary diltiazem or nitroglycerin, in left anterior descending coronary artery, circumflex coronary artery, and right coronary artery were evaluated, diltiazem significantly reduced the TFCs of the left anterior descending coronary artery and circumflex coronary artery compared with nitroglycerin (P < 0.01 for both coronaries). Conclusion Both intracoronary diltiazem and nitroglycerin improve the TFCs in CSFP, and intracoronary diltiazem is superior to nitroglycerin in reducing TFCs in CSFP.

Androgenetic alopecia as an indicator of metabolic syndrome and cardiovascular risk

Abstract Numerous studies have investigated a probable association between androgenetic alopecia (AGA) and cardiovascular disease (CVD) by researching limited and dispersed parameters. We aimed to evaluate both traditional and non-traditional cardiovascular risk factors in male patients with early-onset AGA. This case–control study included 68 participants: 51 male patients with early-onset AGA and 17 healthy male controls. Patients with AGA were classified into three groups according to the Hamilton–Norwood scale and the presence of vertex hair loss. Traditional and non-traditional cardiovascular risk factors were examined in all study subjects. Metabolic syndrome was diagnosed in 25 patients with AGA and in two control subjects (p < 0.05). The carotid intima–media thickness values were found to be significantly higher in patients with vertex pattern AGA than in patients without vertex baldness and controls (p < 0.05). The pulse-wave velocity values were also found to be significantly higher in patients (p < 0.001). A limitation of this study was the small study population. In conclusion, vertex pattern AGA appears to be a marker for early atherosclerosis. This finding supports the hypothesis that early-onset AGA alone could be an independent risk factor for CVD and metabolic syndrome.

The effect of strict volume control on cardiac biomarker and arterial stiffness in peritoneal dialysis patients.

INTRODUCTION Arterial stiffness is a risk marker for cardiovascular events in peritoneal dialysis (PD) patients. Strict volume control strategy has been shown to result in better cardiac functions and control of hypertension in these patients. The aim of the study was to identify the determinants of arterial stiffness and evaluate the changes in cardiac biomarkers in PD patients under strict volume control strategy. METHODS 58 PD patients were enrolled into this prospective observational study. Arterial stiffness determined by aortic pulse wave velocity (PWV), echocardiography, ambulatory blood pressure and NT-pro-BNP levels were measured at baseline and at first year. RESULTS The mean age of the patients was 46.4 ± 14 years. 30 patients were on automated PD (APD) and 28 on continuous ambulatory PD (CAPD) group. In both groups, there were significant differences in PWV values at baseline and at the end of the study. A similar decrease was observed with NT-proBNP and PWV levels. In addition, a significant improvement was found in echocardiographic parameters in all patients. Comparison of APD and CAPD groups with respect to change in one year, showed no difference in echocardiographic findings, while the reduction in PWV, NTproBNP and blood pressure values was higher in the CAPD group. CONCLUSIONS In PD patients, strict volume control leads to a reduction in NT-pro-BNP levels, better control of blood pressure and significant improvements in cardiac functions and arterial stiffness.

Improved arterial stiffness in mitral stenosis after successful percutaneous balloon valvuloplasty

BACKGROUND Rheumatic mitral stenosis (MS) is still a common disease in developing countries with high morbidity and mortality rates. The purpose of the study was to evaluate arterial stiffness in severe MS before and after percutaneous mitral balloon valvuloplasty (PMBV). METHODS Thirty patients with MS in sinus rhythm requiring PMBV and 20 age-gender matched healthy volunteers. The analyze of pulse wave velocities (PWV) were performed using of the carotid artery at the femoral by PWV technique on patients at baseline and a week after PMBV. RESULTS The values of PWV were significantly decreased after successful PMBW in MS patients. Mitral mean gradients and systolic pulmonary artery pressures (sPAP) both on echocardiography and catheterization also had a significant decrease after PMBW. The mitral valve areas were significantly increased after PMBW. There was a highly significant negative correlation between mitral valve areas and PWV values. A highly significant positive correlation was seen between mitral mean gradient on catheterization and PWV (r = 0.830, p 〈 0.001). There was also a significant correlation between sPAP on catheterization and PWV values (r = 0.639, p 〈 0.001). Echocardiographic mitral mean gradients and PWV were highly positive correlated with each other (r = 0.841, p 〈 0.001). The sPAP on echocardiography had also a highly positive correlation with PWV (r = 0.681, p 〈 0.001). CONCLUSIONS Mitral stenosis is a cause of impaired arterial stiffness and after the enlargened mitral valve area arterial stiffness improved in patients with MS.