Hakan Tezcan

Association between salt sensitivity and target organ damage in essential hypertension

Cardiovascular events occur more frequently in sodium-sensitive patients with essential hypertension; recently, sodium sensitivity was shown to be a cardiovascular risk factor independently of other classic factors such as blood pressure and cigarette smoking This study examined the relationship between salt sensitivity status and target organ damage in hypertensive patients. Ninety-six patients (35 men, 61 women) with moderate essential hypertension were studied for salt sensitivity status and the presence of target organ damage, including hypertensive retinopathy, serum creatinine, creatinine clearance, and urinary albumin excretion (UAE). Four different patterns of left ventricular anatomic adaptation were identified by categorizing patients according to the values of left ventricular mass index and relative wall thickness by the means of echocardiography. Forty-five (47%) patients were shown to be salt-sensitive, in contrast to 51 (53%) salt-resistant subjects. Serum creatinine and UAE were significantly higher in the group of salt-sensitive hypertensives (P < .05 and P < .001, respectively). Left ventricular mass index (LVMI), relative wall thickness (RWT), and left atrial index (LAI) were all significantly higher in the group of salt-sensitive hypertensive patients. Concentric hypertrophy was significantly more prevalent in the salt-sensitive group (37.8% v 11.8%; P < .01). The prevalence of hypertensive retinopathy in the salt-sensitive group was 84.4%, in contrast to 59.6% in the salt-resistant group (P < .01). Multivariate regression analysis revealed salt sensitivity as a significant predictor of LVMI, RWT, and UAE, independently of age, body mass index, and mean blood pressure. In conclusion, salt-sensitive hypertensive patients are more prone to develop severe hypertensive target organ damage that may enhance their risk of renal and cardiovascular morbidity.

Bortezomib: a new therapeutic option for POEMS syndrome

Objective: POEMS syndrome with its classical five findings (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) is a rare multisystem disease. Proinflammatory and proangiogenic cytokines play important roles in its pathogenesis. Treatment options are still debated. Methods: We present a 65‐year‐old man with POEMS syndrome who was successfully treated with bortezomib. Results: After seven cycles of this protocol, serum M protein level declined to normal range, and near‐to‐complete remission was achieved. His symptoms of polyneuropathy improved dramatically. Conclusion: Bortezomib may be an effective and safe therapeutic option for patients with POEMS syndrome.

Effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction

Abstract Objective: To evaluate the acute effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction. Design: Prospective, double-blind, placebo-controlled, clinical study. Setting: Cardiology and postmenopausal outpatient clinics of a university hospital. Patient(s): Thirty postmenopausal women with hypertension (diastolic blood pressure of >90 mm Hg) and left ventricular diastolic dysfunction (mitral E/A ratio [the ratio of peak velocity of early mitral diastolic filling to late diastolic filling] of 100 ms) were included in the study. Thirty normotensive postmenopausal women with normal left ventricular diastolic function served as the control group. Intervention(s): Conjugated equine estrogen (0.625 mg) was given orally. Left ventricular diastolic function was assessed by Doppler echocardiography at baseline and 3 hours after the administration of estrogen. Main Outcome Measure(s): Left ventricular diastolic filling as assessed by Doppler echocardiography. Result(s): Estrogen had no effect on heart rate or blood pressure in either study group. The baseline E/A ratios were 0.72 ± 0.26 and 1.22 ± 0.30, and the isovolumic relaxation times were 122 ± 18 ms and 89 ± 14 ms in the hypertensive and normotensive groups, respectively. Estrogen had no significant effect on any of the Doppler parameters in the normotensive group. In the hypertensive group, there was a trend toward normalization of the E/A ratio (from 0.73 ± 0.11 to 0.84 ± 20) and a significant improvement in the isovolumic relaxation time (from 124 ± 20 ms to 105 ± 13 ms) in response to the administration of estrogen compared with placebo. Conclusion(s): A single dose of oral estrogen caused a significant improvement in left ventricular diastolic filling in hypertensive postmenopausal women with diastolic dysfunction.

Effect of angiotensin-converting enzyme inhibition on endothelial function and insulin sensitivity in hypertensive patients

Introduction Evidence suggests an association between insulin resistance, hypertension and impaired endothelial function. Studies have shown that insulin resistance precedes the development of hypertension. By improving insulin sensitivity, it may be possible to improve hypertension and the subsequent damage to vessel walls. Some data indicates beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on insulin sensitivity and endothelial function. We aimed to investigate these effects of ACE inhibition in the same group of patients with essential hypertension. Materials and methods Nine non-smoking, untreated hypertensive patients (38.3 9 years, 4/5 male/female) and 12 age-matched healthy subjects (35.2 6.7 years, 5/7 male/female) were included in the study. Hypertensive patients were given enalapril maleate (5—40 mg/day) for six months. The following parameters were studied at baseline and at the end of treatment period. Whole body insulin sensitivity was measured by a formula derived from an oral glucose tolerance test and named I as the insulin sensitivity index (ISI). Insulin was measured by chemiluminescence and glucose by a glucose oxidase method. Endothelial function was evaluated as flow-mediated dilatation (FMD) of the brachial artery by ultrasonography and expressed as a percentage change relative to baseline diameter. Endothelialindependent vasodilatation was measured after sublingual nitroglycerine. Results FMD was impaired in the hypertensive group compared with healthy subjects (7.3 3.1% vs. 15.3 4.8%, p<0.0005), and ISI values were 1.18 0.6 vs. 4.4 0.9 (p<0.0001) respectively. Both insulin sensitivity and FMD improved after the treatment period compared with baseline values, FMD increased from 7.3 3.1% to 16.0 2.9% (p<0.0005) and ISI from 1.18 0.6 to 4.2 1.0 (p<0.0001). FMD and ISI showed a significant positive correlation (r=0.67, p<0.001) in the hypertensive group. Conclusions Patients with essential hypertension have impaired endothelial function and decreased whole body insulin sensitivity compared with healthy subjects. Treatment for six months with enalapril maleate seems to improve both FMD and ISI. This study confirms the beneficial effects of ACE inhibition on both endothelial function and insulin sensitivity tested in the same group of essential hypertensive patients. The mechanism of these favourable effects of ACE inhibition needs to be clarified.

Temporal effects of low-dose ACE inhibition on endothelial function in Type 1 diabetic patients.

Aim: Increased asymmetrical dimethylarginine (ADMA) is known to disturb endothelial function. ACE inhibitors decrease plasma ADMA levels in diseases associated with endothelial dysfunction. The effects of ACE inhibition on endothelial function and plasma ADMA levels in Type 1 diabetic patients was evaluated in the study. Methods: Thirty Type 1 diabetic patients [29±6 yr; females (F)/males (M): 18/12] and 29 controls (30±6 yr; F/M: 16/13) were recruited. Flow-mediated dilatation (FMD), plasma ADMA and thiobarbituric acid reactive substances (TBARs) were determined at baseline, on day 15 and 90 of 0.5 mg qd trandolapril therapy. Results: Compared to controls, baseline FMD levels were lower (4.7±2.0% vs 11.2±3.9%) (p<0.001), plasma ADMA (271.1±48.1 nmol/l vs 237.5±25.1 nmol/l) (p<0.05) and TBARs levels [4517.1±2366.9 nmol/malondialdehyde (MDA) vs 1775.9±598.7 nmol/MDA] (p<0.001) were higher in diabetic patients. On day 90 of trandolapril treatment, FMD (8.6±4.1%) (p<0.01) increased, ADMA levels (229.6±42.9 nmol/l) (p<0.001) decreased and TBARs levels (1531.8±1036.0 nmol/MDA) (p<0.001) decreased significantly. FMD was negatively correlated with plasma ADMA (r=-0.228, p<0.01), and TBARs levels (r=−0.244, p=0.02), whereas ADMA and TBARs levels were correlated positively (r=0.399, p<0.0001). Conclusions: In conclusion, endothelial dysfunction is associated with elevated plasma ADMA levels in Type 1 diabetic patients. Low-dose ACE inhibition improves endothelial dysfunction and reduces ADMA levels. The antioxidant action of ACE inhibitors may play role in this process.

Diurnal Blood Pressure Abnormalities Are Related to Endothelial Dysfunction in Patients with Non-Complicated Type 1 Diabetes

Patients with diabetes have an increased cardiovascular morbidity and mortality despite interventions to prevent these outcomes. Abnormalities in diurnal blood pressure patterns are also associated with excess cardiovascular mortality. The aim of this study was to determine the effects of diurnal blood pressure patterns on endothelial function and oxidative stress in patients with uncomplicated type 1 diabetes mellitus. Thirty-two normotensive and normoalbuminuric type 1 diabetic patients (21 dipper and 11 nondipper) and 37 healthy (27 dipper and 10 nondipper) volunteers underwent 24-h ambulatory blood pressure monitoring. Their endothelial functions were evaluated using flow mediated dilatation (FMD) and by measuring nitric oxide and thiobarbituric acid reactive substances (TBARS). Dippers were defined as subjects who exhibited an average reduction in both systolic and diastolic blood pressure of greater than 10% between day and night periods. Nondipper type 1 diabetic patients and controls had nighttime systolic and diastolic blood pressure values that were significantly higher than those of dipper diabetic patients (p<0.05) and dipper controls (p<0.01). Values of FMD for nondipper diabetic patients (5.12±2.2%) were significantly lower than those in dipper diabetic patients (10.19±2.5%, p<0.01), nondipper (10.08±2.9%, p<0.001) and dipper controls (11.76±3.8%, p<0.001). Additionally, levels of TBARS in the dipper diabetic group and dipper controls were significantly lower than those in the nondipper diabetic group (p<0.05). In conclusion, only type 1 diabetic patients with a nondipping pattern of blood pressure exhibited changes that may lead to endothelial dysfunction and atherosclerosis.

The Effects of Amlodipine on Left Ventricular Mass and Diastolic Function in Concentric and Eccentric Left Ventricular Hypertrophy.

Background: The effects of the antihypertensive therapy with amlodipine (5-10 mg/day) on left ventricular mass and diastolic function were examined in 30 mild to moderate essential hypertensive patients who have left ventricular hypertrophy (LVH) and diastolic dysfunction. Methods and Results: Each patients left ventricular mass was measured, and left ventricular diastolic function was assessed by echocardiographic Doppler examination at entry, and at 3 and 6 months after the initiation of the treatment. Amlodipine reduced both blood pressure (from 164 ± 14/10 ± 6 mmHg to 134 ± 9/83 ± 4 mmHg) and left ventricular mass index (from 160 ± 30 g/m2 to 137 ± 26 g/m2) significantly at 3 months and both parameters maintained at these levels for 6 months. When the patients were classified according to the type of the LVH. a significant regression in left ventricular mass index was seen only in the patients who had concentric LVH with a relative wall thickness ≥ 0.44 (n = 16), but not in the eccentric LVH group (n = 14), although both groups were not significantly different from each other regarding the basal hemodynamic parameters. baseline left ventricular mass index and the decrease in blood pressure in response to amlodipine treatment. The mitral inflow E/A ratio did not show any significant change in either group. Conclusions: Across the three chronic heart disease risk strata, lovastatin appears to be significantly more potent than fluvastatin, on a per milligram basis, in lowering cholesterol levels.

QT Dispersion in Renal Transplant Recipients

An increased QT dispersion (QTd) is associated with a variety of cardiac diseases and predicts sudden death. Although chronic renal failure patients and patients on hemodialysis are shown to have an increased QTd, evidence of increased QTd in renal transplant patients is scarce. In this study, renal transplant patients were evaluated to find out if they had an increased QTd. Thirty-four renal transplant recipients aged 35 ± 8 years and 34 healthy control subjects aged 34 ± 8 years were included in the study. The mean time after transplantation was 51.8 ± 40.4 (range 5–154) months. The QT interval was measured by 12-lead electrocardiogram, and the QTd was defined as the difference between the maximum and minimum QT interval. Bazett’s formula was used to correct for the heart rate (QTc). Both QTd and QTc dispersion (QTcd) in renal transplant patients were compared with those of control subjects. All patients underwent transthoracic echocardiographic assessment and 24-hour ambulatory blood pressure monitoring. Renal transplant recipients had similar QTd (37 ± 15 vs. 39 ± 17 ms) and QTcd (50 ± 18 vs. 55 ± 20 ms) compared to control subjects. QTd and QTcd were similar in patients with and without left ventricular hypertrophy (QTd 37 ± 14 vs. 36 ± 17 ms and QTcd 50 ± 14 vs. 49 ± 21 ms, respectively). No association was found between QTd and left ventricular mass index or blood pressure measurements. The QTd was not found to be increased in renal transplant recipients as compared with that of healthy controls in this study. Normalization of the QTd after renal transplantation may be through the correction of several factors responsible for increased QTd in uremic patients.

A study to classify Non-Dipper/Dipper blood pressure pattern of type 2 diabetes mellitus patients without Holter device

The aim of this study was to design an expert system to predict the Non-Dipping or Dipping pattern by using several basic clinical and laboratory data through an artificial intelligence algorithm. Data Mining is a technique which extracts information from data sets by using a combination of both statistical analysis methods and artificial intelligence algorithms. Also in this study, the decision tree and naivebayes classification algorithms of this technique were used. Firstly, sixty-five patients (mean age 51±7 years, 40 females,) were included in the study. Systolic and diastolic dipping were found in 13 and 15 % of the patients, respectively. In the advancing process of the experiment, the number of instances were reduced, because of some missing data of the patients. The data sets were tested using the J48 decision tree algorithm. This classification algorithm was implemented on 56 instances, and also the number of attributes was reduced from 35 to 23. 66 % of the instances (37) were reserved for training and 44 % of the instances (19) were reserved for testing. When the algorithm was run, the Non-Dipper/Dipper pattern of the instances were correctly predicted in a rate of 73.6842 %. Model was built in 0.02 seconds. This pilot study shows that a machine learning algorithm can help in the prediction of diurnal blood pressure pattern relying on some basic demographic, clinical and laboratory data, with a reasonable accuracy.

Interaction between C-reactive protein and endothelin-1 in coronary artery disease.

Background: Increased concentrations of serum C-reactive protein (CRP) have been reported to predict major cardiovascular events in patients with coronary artery disease (CAD). Increased concentrations of endothelin-1 (ET-1) are also associated with poor prognosis after myocardial infarction. Hypothesis: We tested the hypothesis that ET-1 might contribute to CRP in prediction of adverse outcome in CAD. Methods: Serum high sensitive CRP and plasma ET-1 levels of 40 patients who have stable CAD and 25 control subjects were measured, and correlation analysis between these molecules was performed. Results: Mean high sensitive CRP was 8.64 ± 12.73 mg/l, and mean ET-1 was 8.24 ± 7.06 pg/ml in the CAD group. We found that there was no statistically significant correlation between high sensitive CRP and ET-1 in either CAD group (p = 0.82), or the control group (p = 0.85). In a subgroup of 13 patients who were not under statin treatment, we found a strong correlation between the levels of these molecules (p = 0.01). Conclusion: Our study does not clearly support or exclude a link between CRP and ET-1 in patients who have stable CAD.