Endothelial damage in white coat hypertension: role of lectin-like oxidized low-density lipoprotein-1.

The aims of this study included an examination of soluble lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (sLOX-1) levels in hypertensive (HT) patients. Another aim examined sLOX-1 associations with oxidized LDL (oxLDL), nitric oxide synthase (eNOS) and nitric oxide (NOx). A final aim was to compare these parameters between HT patients, white-coat hypertensive (WCH) patients and healthy controls. The three groups, HT, WCH and controls, were comprised of 35 patients each. sLOX-1 and oxLDL levels were significantly increased in WCH and HT patients compared with controls. The eNOS activation was significantly lower in HT than in the control group. sLOX-1 and oxLDL levels were significantly negatively correlated with eNOS levels in the WCH and HT groups. Carotid intima-media thickness (CIMT) measurements were significantly higher in the WCH and HT groups compared with controls. There was a significant positive correlation between CIMT and sLOX-1 and oxLDL; however, there was a negative correlation with eNOS in WCH. Regression analysis revealed that sLOX-1 was the variable that had a significant effect on blood pressure (P<0.001, odds ratio (95% confidence interval=23.273 (5.843-92.688)). A possible endothelial impairment may act as a cardiovascular risk factor in WCH. Necessary measures should be considered in terms of atherosclerosis risk with HT, especially in early identification of endothelial damage by looking at sLOX-1 levels. We believe sLOX-1 levels are strong biomarkers for determining early endothelial damage in HT, and especially in WCH patients.

Hypertension and hemostatic/fibrinolytic balance disorders.

BACKGROUND: Hypertension is one of the principal risk factors for cardiovascular disease. We aimed to evaluate the impact of hypertension on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), tPA/PAI-1 complex and fibrinogen. METHODS: Patients enrolled into the study were divided into four groups: 22 essential hypertensive (EH), 22 white coat hypertensive (WCH), 22 renovascular hypertensive (RH) and 22 normotensive control subjects. Plasma PAI-1, tPA, tPA/PAI-1 complex levels were measured by enzyme linked immunosorbent assays. RESULTS: There was no difference in the systolic and diastolic blood pressure measurements of the EH and RH groups. The four groups were comparable for age, gender, smoking habits and BMI. Patients with EH, RH and WCH had increased plasma levels of PAI-1, tPA, tPA/PAI-1 complex and fibrinogen compared with controls. No fibrinolytic parameter was associated with blood pressure in hypretensive subjects. CONCLUSION: This prospective study showed that fibrinolytic markers such as PAI-1, tPA, tPA/PAI-1 complex are independently associated with the development of hypertension. This supports the hypothesis that disturbances in fibrinolysis precede a cardiovascular event. Therefore, hypertension may be associated with impaired fibrinolysis.

Blunted nocturnal fall of blood pressure in isolated clinical hypertension.

OBJECTIVE: The aim of the study is to assess the relation between diurnal blood pressure variations and target organ damage in isolated clinical hypertension (ICH). MATERIAL AND METHODS: Ninety patients with ICH (clinical systolic blood pressure [SBP] superior or equal to [>=] 140 and/or diastolic blood pressure [DBP]> = 90 mm Hg) and ambulatory daytime SBP and DBP <135/85 mm Hg were enrolled in this study. Patients with ICH were classified into two groups as dippers (13 males, 34 females) and nondippers (7 males, 36 females). Nondippers were defined by a reduction in mean blood pressure of less than 10% from day (06:00-24:00) to night (24:00-6:00); and the rest of the patients were classified as dippers. Left ventricular mass index (LVMI) and early diastolic velocity/late diastolic velocity (e/a) were determined by echocardiography; intima-media thickness (IMT) and compliance of the carotid artery (distensibility coefficient [DC] and compliance coefficient [CC]) were measured by ultrasound. Renal function was measured by glomerular filtrate rate (GFR) and urinary albumin excretion (UAE). Retinal changes were determined by fundoscopy. RESULTS: There was no difference between the demographic and biochemical characteristics of the two groups. IMT was significantly higher in nondippers (p <0.005). The nondippers had significantly lower levels of DC (p <0.005) and CC (p <0.0005). LVMI was above normal in both groups with no significant difference. The e/a ratio, although normal in both groups, differed significantly between them (p <0.0005). HTRP, microalbuminuria and GFR <90 mL/min/1.73 m2 were more frequent in nondipper ICH patients. CONCLUSION: The results of the study suggest that in ICH nondipping is associated with a decrease in arterial compliance. The global risk load for target organ.

Levels of paraoxonase, an index of antioxidant defense, in patients with active sarcoidosis.

OBJECTIVE: Oxidative mechanisms are currently discussed as playing a crucial role in the genesis of inflammatory lung diseases. We aimed to evaluate the oxidant-antioxidant balance in the pathogenesis and activity of sarcoidosis and to search if the change in the level of PON can be taken as an activity marker. METHODS: 26 active sarcoidosis subjects aged 41.3+/-12.9 years, 37 inactive subjects aged 39.6+/-11.7 years and 48 control subjects aged 48.9+/-2.5 years were recruited in our study. Malondialdehyde (MDA), paraoxonase1 (PON1) and oxidized low density lipoprotein (oxLDL) levels in serum were analyzed by spectrophotometric, kinetic, and ELISA methods, respectively. RESULTS: PON1 levels were significantly lower in the active disease state than both the inactive form and control groups. MDA levels were significantly higher in active sarcoidosis than both the inactive disease and control groups, and oxLDL levels were significantly higher in the active disease group than the inactive group and control group. The level of PON1 in the inactive disease group is not significantly different from the control group while the oxLDL and MDA levels of inactive group is significantly higher than the control group (p<0.001). There was a negative correlation between the PON1 activities and MDA values in both active and inactive groups (p=0.008). CONCLUSION: Oxidative stress increases in sarcoidosis might be due to both increase in lipid peroxidation and decrease in antioxidant status (PON1) and the relationship between oxidative status and the activation of the disease should be discussed by comparing the previously known activation criteria.

Oxidative stress in human in sustained and white coat hypertension.

Oxidative stress is thought to play a critical role in the pathogenesis of hypertension. Protein oxidation is defined here as the covalent modification of a protein induced either directly by reactive oxygen species or indirectly by reaction with secondary by-products of oxidative stress. The aim of our study was to evaluate the protein oxidation and to examine the function of the antioxidative system in sustained and white coat hypertensives (WCH) and compare with normotensives. This study was designed to investigate the protein oxidation parameters [protein carbonyls (PCOs)] in sustained hypertensives (17 males and 20 females) and WCH (18 males and 19 females). PCO and the endogenous antioxidant components protein thiol (P-SH), CuZn-superoxide dismutase (CuZn-SOD) and glutathione (GSH) were analysed using spectrophotometric and kinetic methods. Sustained hypertensive and WCH groups exhibited higher protein oxidation and lower P-SH, CuZn-SOD and GSH activities than normotensives. With regard to these parameters, there was no significant difference between sustained hypertensive and WCH groups. Blood pressure correlates positively with PCO groups and negatively with others. There exists an imbalance between oxidants and antioxidants in WCH because of the increase of oxidants associated with the decrease of antioxidant capacity. This may cause endothelial dysfunction just like in sustained hypertension. It may be necessary to add antioxidants to conventional antihypertensive therapy to balance the oxidative status in WCH.

Increased circulating concentrations of asymmetric dimethylarginine (ADMA) in white coat hypertension.

Elevated plasma levels of the endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) contribute to endothelial dysfunction and seem to be a predictor for cardiovascular mortality. Elevated ADMA plasma concentrations have been demonstrated in patients with hypertension. However, the plasma concentrations of ADMA in white coat hypertension (WCH) has not been previously studied. The aim of this study was to evaluate ADMA in WCH and compare with normotensive (NT) and hypertensive (HT) patients. We also evaluated the relation between ADMA and NO in these three groups. For this purpose, 34 NT, 34 white coat hypertensive (clinical hypertension and ambulatory daytime blood pressure <135/85 mmHg) and 34 HT patients were recruited in this study. The subjects were matched for age, gender, body mass index (BMI) and the patients with smoking habit, dyslipidaemia and diabetes mellitus were excluded. The ADMA levels were determined by high performance liquid chromatography. Plasma ADMA levels were significantly higher in WCH group than in the NT group (3.21+/-0.49 micromol/l vs 2.84+/-0.58 micromol/l, P=0.046). It was significantly higher in the HT group than in the NTs (4.24+/-0.38 micromol/l, P<0.001). There was also a significant difference between the HT and WCH groups (P<0.001). The WCH subjects had significantly higher levels of NO than the HTs (41.68+/-2.23 vs 32.18+/-2.68 micromol/l; P<0.001) and significantly lower values than the NTs (48.24+/-4.29 micromol/l; P<0.001). In WCH and HT group, there was a negative correlation between ADMA and NO (r=-0.515, P=0.003 and r=-0.389, P=0.034, respectively). In NT subjects, there was no correlation between these two parameters (r=-0.287, P=0.124). The correlation between ADMA and NO was stronger in WCH group than in HT group. Although NO levels in HT patients were lower than WCHs and ADMA levels were higher in HT patients than WCHs, the negative correlation of these two parameters were more pronounced in WCH group. Decreased NO and increased ADMA levels in WCH may indicate endothelial dysfunction. Our data indicate also that WCH represent an intermediate group between NT and HT when endothelial dysfunction is concerned.

Endothelium and angiogenesis in white coat hypertension.

Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. The aim of this study was to compare the risk conferred by white coat hypertension (WCH) vs sustained hypertension in the development of the endothelial dysfunction and abnormal angiogenesis by evaluating nitric oxide (NO=NO2+NO3), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and E-selectin levels in plasma. The study group included 102 subjects, 34 with WCH (17 male and 17 female patients) aged 49+/-11 years, 34 sustained hypertensives (HT) (15 male and 19 female patients) aged 47+/-11 years and 34 normotensive control subjects (NT) (16 male and 18 female patients) aged 48+/-10 years. WCH was defined as clinical hypertension and daytime ambulatory blood pressure less than 135/85 mmHg. The subjects were matched for age, gender, body mass index and the patients with smoking habit, dyslipidaemia, and diabetes mellitus were excluded from the study. The NO, ET-1, VEGF and E-selectin levels were analysed by ELISA technique. The WCH subjects had significantly higher levels of NO than the HT (41.68+/-2.23 vs 32.18+/-2.68 micromol/l; P<0.001) and significantly lower values than the NT (48.24+/-4.29 micromol/l; P<0.001). ET-1 levels of the WCH group were significantly higher than the NT (8.10+/-0.92 vs 5.95+/-0.26 ng/ml; P<0.001) and significantly lower than the HT (11.46+/-0.59 ng/ml; P<0.001). Considering with VEGF, the WCH group had significantly higher levels than the NT (195.88+/-11.84 vs 146.26+/-18.67 pg/ml; P<0.001), but the difference from the HT group was not significant (203.35+/-7.48 pg/ml; P=0.062). E-selectin in the WCH group was significantly lower than the HT (4.77+/-0.52 vs 8.49+/-2.85; P<0.001), but the difference from the NT group was not significant (3.86+/-0.67; P=0.077). Our data demonstrate that WCH is associated with endothelial dysfunction and abnormal angiogenesis. The degree of these changes is not as severe as observed in hypertensive population.

Oxidative stress in white coat hypertension; role of paraoxonase.

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.

Gaucher disease and brucella: just a mere coincidence?

Gaucher disease type I and brucellosis are chronic diseases with similar symptoms and physical signs though the former is the most common lysosomal storage disease and the latter is an infectious disease. The similarities between these diseases make differential diagnosis difficult. Immunodeficiency is a feature of Gaucher disease type I and increases the susceptibility towards infections. A Gaucher disease type I patient with brucellosis is presented with improvement after treatment of brucellosis.

Benign cystic mesothelioma: a rare cause of ascites in a case with familial Mediterranean fever.

Benign cystic mesothelioma (BCM) is a rare neoplasm of the peritoneum, consisting of solitary or multiple cysts arising from mesothelial cells. Here we report a patient with a previous diagnosis of familial Mediterranean fever (FMF) presenting with abdominal distension and ascites which were found to be due to BCM. The co-existence of these two entities has not been reported previously. Ascites as the presenting feature of BMC is also a rare observation.

Target organ damage and changes in arterial compliance in white coat hypertension. Is white coat innocent?

The aim of this study was to perform an extensive evaluation of target organ status, metabolic abnormalities and hemodynamic alterations in white coat hypertension (WCH). Fifty normotensive (NT), 90 WCH (ambulatory daytime blood pressure < 135/85 mmHg) and 101 hypertensive (HT) subjects underwent extensive biochemical, echocardiographic, fundoscopic examination. In a subgroup study, arterial compliance and intima-media thickness (IMT) were measured by Doppler ultrasound in left common carotid artery. WCH subjects were found to have higher body mass index (BMI) than the NTs (p = 0.042). Left ventricle mass index (LVMI) was greater in the WCHs than the NTs (p < 0.001), but significantly less than the HTs (p < 0.001). Hypertensive retinopathy was observed in the WCHs, but was less severe and rare compared to the HTs (13% vs 27%). Both WCHs and HTs had high levels of urinary albumin excretion (UAE) (p = not significant). Total cholesterol was higher in WCHs than in the NTs (p = 0.04) The distensibility coefficient (DC) of the WCHs was significantly greater than the HTs (p < 0.01), while significantly smaller than the NTs (p < 0.01). The compliance coefficient (CC) of the WCHs was significantly higher than the HTs (p < 0.01), and significantly less than the NTs (p < 0.01). The IMT in the HTs was significantly higher than the WCHs (0.81 +/- 0.05 vs 0.70 +/- 0.04 mm; p < 0.001) and the NTs (p < 0.001). The difference between the NTs and the WCHs was not significant. Our data indicate that patients with WCH represent an intermediate group between NTs and sustained HTs where target organ damage and cardiovascular risk is concerned.

The antihypertensive effects of doxazosin on the arterial system: changes in peripheral vascular resistance and wall tension.

Background: Hypertension is characterized by structural and functional abnormalities that affect the entire cardiovascular system, including the large arteries. The antihypertensive efficacy of doxazosin, a selective alpha(1) antagonist, and its effects on the arterial system were investigated. Method: In our double-blind, randomized, placebo-controlled study including 30 hypertensive patients (doxazosin group: nine males, 11 females; mean age 45+/-12 years; placebo group: four males, six females; mean age 47+/-9 years), the systolic, diastolic and mean blood pressure (BP), heart rate, diameter and area of the brachial artery, peak systolic velocity, end-diastolic velocity, pulsatility index (PI), resistance index (RI), S/D (systolic velocity/diastolic velocity), flow volume, local resistance, and wall tension were recorded before and 4 h after the administration of 2 mg doxazosin or placebo. The two groups were statistically compared. Results: In the doxazosin group, systolic, diastolic and mean pressures decreased significantly (P<0.001), while heart rate remained unchanged. Local resistance (P<0.001), RI (P<0.05), PI (P<0.05), and wall tension (P<0.001) all decreased significantly, while flow volume increased significantly (P<0.05). However, no significant changes were observed in arterial diameter, surface area, peak systolic velocity, end-diastolic velocity or S/D ratio. The placebo group did not show a significant difference in any of the parameters listed above. Conclusion: The antihypertensive effect of doxazosin is accompanied by a reduction in brachial arterial wall tension that occurs without any change in arterial diameter. The lack of change in the diameter of the artery leads us to suggest different effects on other vasomotor determinants.