Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients. METHODS: 225 subjects with stage 3-5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction. RESULTS: There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR ≥3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity. CONCLUSIONS: NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.

The relationship between microalbuminuria, left ventricular hypertrophy, retinopathy, and sex hormone status in newly diagnosed hypertensive women.

An increased incidence of hypertension (HT) in postmenopausal female population has been shown in previous studies and this has been ascribed to an association with altered status of estrogen (E2) and other female sex hormones. Hypertension is associated with certain target organ damage (TOD) and related clinical conditions. The aim of this study was to determine the relationship between microalbuminuria, left ventricular hypertrophy (LVH), retinopathy, and sex hormone status in newly diagnosed hypertensive women. A total of 66 hypertensive women (39 postmenopausal and 27 premenopausal) were included in the study. Along with the tests recommended in the HT guidelines, LVH, hypertensive retinopathy, and microalbuminuria were investigated in all the patients. Sex hormones (follicle stimulating hormone, luteinizing hormone, progesterone, and E2) of the patients were also measured. The results show that there was no statistically significant difference between the two groups in regard to TOD except microalbuminuria. The frequency of microalbuminuria in premenopausal group patients was higher than that of the postmenopausal group patients (P = .038). This study suggests that TOD caused by HT is a very important health problem, seeming to be related with female sex hormones.

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.

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.

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.

An additional LDL-lowering effect of amlodipine; not only an antihypertensive?

Hypertension is a modifiable risk factor for cardiovascular diseases and is associated with several metabolic disorders like dyslipidemia. Higher levels of triglyceride and low-density lipoprotein (LDL) are quite strong factors for the development of cardiovascular diseases. In this study, we investigated the effects of valsartan and amlodipine on the lipid profile in patients with newly diagnosed essential hypertension. We observed a beneficial effect of amlodipine on the lipid profile with a significant reduction of LDL compared to valsartan. In the treatment of hypertension, prior knowledge of the plasma cholesterol levels can be important in antihypertensive drug choice.

Amlodipine seems to be superior to valsartan in decreasing microalbuminuria in newly diagnosed hypertensive patients: a novel effect to be explained with hyperfiltration?

BACKGROUND: Microalbuminuria (MA) is common in hypertensive population and is a marker for endothelial dysfunction and a predictor of increased cardiovascular risk. A great body of data shows the importance of MA as a strong predictor of renal and cardiovascular disease (CVD) risk in hypertensive population. AIM: In this study, we aimed to compare the anti-albuminuric effects of an angiotensin II receptor antagonist, valsartan, with a calcium channel blocker, amlodipine, in newly diagnosed hypertensive patients. MATERIAL AND METHODS: Totally, 20 patients were recruited into the study. Patients were randomized to one of the following intervention protocols: An (a) angiotensin II receptor blocker (valsartan, 80-320 mg/day) or (b) calcium channel blocker (amlodipine, 5-10 mg/day), for 12 weeks immediately after baseline measurements. Ten patients were randomized into valsartan group and 10 patients into the amlodipine group. Twenty-four-hour urinary albumin excretion (UAE) levels of the patient groups were measured before treatment and on the 12th week. RESULTS: Patients of the two groups were matched for age and body mass index. In the amlodipine group, baseline urine microalbumin levels were higher compared to valsartan group, although the difference was not statistically significant (p = 0.082). At the 12th week, there was a significant decrease in urine microalbumin levels in the amlodipine group, but no significant change was observed in the valsartan group. CONCLUSION: Amlodipine seems to be superior to valsartan in decreasing UAE. To reduce cardiovascular risks, endothelial dysfunction, and microinflammation, these factors are taken into consideration while prescribing antihypertensive drugs in hypertensive patients.

Amlodipine increases vitamin D levels more than valsartan in newly diagnosed hypertensive patients: pointing to an additional effect on bone metabolism or a novel marker of inflammation?

Hypertension is a major challenge for public health. Appropriate antihypertensive treatment seem to provide a better life with lower morbidity and mortality rates. Another pathologic condition, osteoporosis, mainly affects postmenouposal women, and constitutes a growing body of risks after a particular age. As bone is a dynamic organ system that is directly related to calcium and phosphor metabolism, imbalance in these two parameters upon aging or menopause finally may lead to osteoporosis. Today, both osteoporosis and high blood pressure are major morbidities, especially in the elderly population. There are some intriguing results on the effects of antihypertensive agents on bone metabolism in the literature. In this study, we aimed to investigate the effects of widely used antihypertensive agents, valsartan and amlodipine on vitamin D levels in newly diagnosed hypertensive population. We found that amlodipine increased vitamin D levels significantly in patients with a newly diagnosed hypertension on a 12-week treatment duration compared to valsartan.

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.

Evaluation of electrocardiographic parameters in patients with diabetes insipidus.

BACKGROUND: There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors. METHODS: Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared. RESULTS: Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively). CONCLUSIONS: DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

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 (ß coefficient: 0.092, p = 0.358; and ß 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.

Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus.

Central Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein.

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.

Serum gamma-glutamyltransferase levels are inversely related to endothelial function in chronic kidney disease.

BACKGROUNDS: Gamma-glutamyltransferase (GGT) is an enzyme responsible for the extracellular catabolism of the antioxidant glutathione and recently implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is a prodromal feature of atherogenesis. Since oxidative stress is highly present in uremia and causally linked to endothelial dysfunction, we hypothesized that GGT may be a factor implicated in this process. METHODS: Serum GGT and C-reactive protein (CRP) levels, estimated glomerular filtration rate (eGFR), and 24-h proteinuria were measured in 214 nondiabetic stages 3-5 CKD patients. The endothelium-dependent vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasound. We investigated the relationship between FMD and circulating serum GGT. RESULTS: Serum GGT levels were negatively associated with FMD (r = -0.41, p < 0.001) and eGFR (r = -0.34, p < 0.001) in univariate analysis. Multivariate regression analysis showed that the association between GGT and FMD persisted after adjustment for age, sex, smoking, renal function (eGFR), inflammation (CRP), proteinuria, and homeostatic model assessment index. CONCLUSION: Circulating GGT levels significantly associate with endothelial dysfunction, an important early feature of the atherogenic process. GGT might be an early marker of oxidative or other cellular stress that it is possibly directly related to the pathogenesis of endothelial dysfunction.

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

ObjectiveThere 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 methodsSixty 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.ResultsFasting 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).ConclusionPrediabetes 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.