Endothelial Dysfunction In Hypertensive Patients Research Articles

Endocan as a marker of endothelial dysfunction in hypertension: a systematic review and meta-analysis.

Hypertension is one of the foremost risk factors for cardiovascular disease and a significant cause of death worldwide. Importantly, endothelial dysfunction (ED) is one of the primary manifestations that may precede the development of hypertension. Endocan is a novel endothelial dysfunction and inflammation biomarker secreted from endothelial cells. Whether endocan may serve as a biomarker of hypertension is currently debated. This systematic review and meta-analysis aimed at linking endocan to ED in hypertensive patients. International databases, including PubMed, Scopus, Embase, and Web of Science, were systematically searched for studies investigating Endocan serum or plasma levels in hypertensive patients and healthy controls. Random effect meta-analysis was performed to calculate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies assessing the association between endocan levels and hypertension were included in which 3130 individuals with a mean age of 50.48 ± 8.45 years were assessed. Hypertensive patients presented with higher circulating endocan levels (SMD 0.91, 95% CI 0.44-1.38, p-value < 0.01) compared with healthy controls. Interestingly, our data demonstrated that removing three studies assessing endocan levels in hypertensive patients with different comorbidities or special populations resulted in the same statistically higher endocan levels (SMD 1.16, 95% CI 0.66-1.65, p-value < 0.01). Overall, this systematic review and meta-analysis indicated that in hypertensive patients circulating endocan levels are significantly elevated. Thus, suggesting endocan as an easy-to-use biomarker to detect ED in hypertension. Despite this, more research is warranted to address this potential ability specifically.

Significance of Endothelial Dysfunction in Hypertensive Patients with Knee Osteoarthritis

Significance of Endothelial Dysfunction in Hypertensive Patients with Knee Osteoarthritis

The role of NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms in endothelial dysfunction pathway and carotid intima-media thickness in hypertensive patients.

The mechanisms orchestrating the balance between nitric oxide and endothelium-derived contracting factors, and genetic predisposition to endothelial dysfunction in hypertensive patients remain to be determined. One-hundred hypertensive patients participated in the case-control study to clarify the risk of endothelial dysfunction and carotid "intima media" thickness (IMT) changes depending on NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms. It is found that presence of NOS3 gene's С-allele significantly elevates the risk of atherosclerotic plaques on carotid arteries (OR95%CI: 1.24-11.20; р = 0.019) and the probability of low NOS3 gene expression (OR95%CI: 17.72-520.0; р < 0.001). Homozygous carriage of С-allele of GNB3 gene is protective and corresponds to the lowest chances of the carotid IMT increase, atherosclerotic plaques formation and sVCAM-1 elevation (OR = 0.10-0.34; OR95%CI: 0.03-0.95; р ≤ 0.035-0.001). Vice versa, Т-allele of GNB3 gene significantly augments the risk of the carotid IMT increase (OR95%CI: 1.09-7.74; р = 0.027) including development of atherosclerotic plaques, associating GNB3 (rs5443) with cardiovascular pathology.

ENDOTHELIAL COMPLICATIONS IN HYPERTENSIVE PATIENTS WITH OBESITY OR NORMAL BODY WEIGHT AFTER COVID-19

Objective: To study the contribution of a COVID-19 to endothelial dysfunction in hypertensive patients with obesity or normal body weight. Design and method: 59 hypertensive patients, male and female, aged 20–50 years (40.2 ± 6.7 years), with blood pressure (BP) under control, without diabetes, non-smokers were included in the study. All of them were divided into three groups: I (n = 13) - patients with obesity (body mass index (BMI) &gt; 30 kg/m2) and 1 month after COVID-19; II (n = 11) - patients with normal body weight (BMI &lt; 25 kg/m2) and 1 month after COVID-19; III (n = 25) - patients with obesity (BMI &gt; 30 kg/m2) without COVID-19. Patients of Ith and IIIth groups were comparable in BMI and BP levels. LDL-cholesterol and triglycerides levels, office systolic BP and diastolic BP, flow-mediated dilation (FMD) study to assessed endothelial function, were performed in all groups. Calculation was done with software STATISTICA 6.0. Results: Post-COVID-19 patients with obesity had significantly higher levels LDL-cholesterol and triglycerides, systolic BP and diastolic BP then in post-COVID-19 patients with normal body weight: 3.5 ± 0.7 mmol/l vs 3.02 ± 0.62 mmol/l (p &lt; 0.05), 3.5 ± 2.9 mmol/l vs 1.10 ± 0.3 mmol/l (p &lt; 0.05), 141 ± 9.6 mmHg vs 123 ± 10.3 mmHg (p &lt; 0.05), 89.5 ± 10.01 mmHg vs 76 ± 8.8 mmHg (p &lt; 0.05) respectively. FMD were significantly lower in patients with obesity and COVID-19 (3.6 ± 2.9%, p &lt; 0.05) then in patients with normal body weight and COVID-19 (8.7 ± 3.4%, p &lt; 0,05) and in patients with obesity without COVID-19 (4.2 ± 3.6%, p &lt; 0.05). Conclusions: Our study highlights that chronic impairment of systemic vascular endothelial function in patients with obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. However, obesity itself is one of important factors contributing to deterioration of endothelial function.

Analysis of Urea, Creatinine, and Platelet Indices in Hypertensive Patients

Hypertension may lead to complications of kidneys and blood vessels. Measurement of urea, creatinine, and platelet indices can be markers of renal function and endothelial dysfunction in hypertensive patients. This study aimed to analyze the profile and correlation between renal function parameters such as urea and creatinine and platelet indices (MPV, PDW, and PCT) with blood pressure in hypertensive patients. One hundred and thirty-third hypertensive patients treated at Wahidin Sudirohusodo Hospital from April to July 2019 were involved in this cross-sectional study. Researchers collected demographic data, blood pressure degrees (based on ESC 2018), systolic and diastolic blood pressure, and urea, creatinine, and platelet index value (MPV, PDW, and PCT) data from the medical record. Descriptive analysis, Spearman test, Fisher exact test, and Kruskal-Wallis test were used confidence interval of 95%. A total of 133 participants were involved in this research. There were significant difference between the mean age (p=0.023), MPV (p=0.032), and PCT (p=0.019) to the degree of hypertension, while gender (p=0.185), urea (p=0.106), creatinine (p=0.498), platelet (p=0.094) and PDW (0.826) showed no significant difference. The bivariate correlation test showed that urea (rs= -0.232 p=0.007) and creatinine (rs= -0.180 p=0.038) had a positive correlation with systolic blood pressure. Platelets index, MPV (rs=0.285 p=0.001), and PDW (rs=0.179) were positively correlated to systolic blood pressure. Also, urea levels and creatinine were positively correlated with MPV value. There was an increase in MPV along with the increase of urea, creatinine. An increase in MPV could be a predictor of endothelial damage and the risk of atherothrombosis.

Ambulatory Blood Pressure Monitoring and Endothelial Dysfunction in Hypertensive Patients with Diabetes Mellitus Type 2

Aim: Diabetic hypertensive patients have pronounced changes in ambulatory blood pressure profile and endothelial function. But the correlation between the parameters of ambulatory blood pressure monitoring (ABPM) and endothelial dysfunction in diabetic hypertensive patients have not been fully clarified. We studied ABP and endothelial function in a group of diabetic hypertensive patients. Methods: Patients with a glomerular filtration rate (GFR) of less than 30 mL/min per 1.73 m(2) were excluded. 120 patients were included into the research. Of these, the first (basic) group made up diabetic hypertensive patients in which there were 34 males and 26 females, the mean age was 56.1±1.3 years, the duration of arterial hypertension (AH) was 12.3±2.1 years and the duration of type 2 diabetes mellitus (DM2) was 4.4±0,7 years. The second (control) group made up 60 non-diabetic hypertensive patients in which there were 27 males and 33 females, the mean age was 55.2±1.2 year and duration of AH was 11.1±0.9 years. The patients in both groups were similar in age, duration of AH. Results:The analysis of the results of the 24-hour ABPM revealed that the number of patients with increased 24 hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability was more among diabetic hypertensive patients than in non-diabetic hypertensive patients (76.7 % versus 21.1 and 70.0 % versus 22.5 %, respectively, p <0,05). There were not any significant changes in pulse rate, SBP and DBP. The amount of non-dipper and night-peaker patients was significantly higher in the basic group than in the control one (60.0 % versus 25.4 %, respectively, p <0,05). It was established that the number of patients with DBP daily value <10 was more significant in diabetic hypertensive patients versus non- diabetic hypertensive patients (33.3 % versus 18.2 %, respectively). We also determined nitric oxide metabolites concentration (nitrites and nitrates (NO)) and endothelin (ET-1) in serum and in 24 h-urine collection to assess endothelial function. So, the concentration of ET-1 in serum was significantly higher in diabetic hypertensive patients compared with non-diabetic hypertensive patients (2.49±0.01 pg/ml versus 1.5±0.07 pg/ml, respectively, p <0,05). NO metabolites concentration in serum and urine was significantly lower in the basic group than in the control group (12.7±1.5 uM versus 19,9±1,8 uM and 428.2±27.9 uM versus 792.1±39.4 uM, respectively, p <0,05). The direct association between SBP, DBP and ET-1 in urine were determined in diabetic hypertensive patients (r = 0.7, r = 0.99, respectively, p < 0.001). The correlation between daily index of SBP and ET-1 in urine (r = -0.58, p < 0.001), daily index of DBP and ET-1 in serum (r = -0.47, p < 0.001) were established in the basic group. Conclusion: The correlation between the parameters of ABPM and endothelial dysfunction in diabetic hypertensive patients were established in this study.

Circulating senescent angiogenic T cells are linked with endothelial dysfunction and systemic inflammation in hypertension.

Objective:Angiogenic T cells (Tang cells), a recently discovered T-cell subset, have been reported involved in the repair of endothelial injury. The purpose of this study was to explore the correlation of immunologic senescence and pro-inflammatory capacity of Tang cells with endothelial dysfunction in hypertensive patients.Methods:Immunological characteristics of Tang cells (CD3+CD31+CXCR4+) from hypertensive patients with or without endothelial dysfunction were elucidated by surface immunophenotyping and intracellular cytokine staining. Endothelial function was measured by flow-mediated dilation (FMD).Results:The frequency of CD28null subset in CD4+ Tang cells was notably elevated in hypertensive patients with endothelial dysfunction, which was negatively associated with FMD. The high frequency of CD28nullCD4+ Tang cells was an independent risk factor of endothelial dysfunction with good diagnostic performance in ROC curve analysis. Immunophenotyping revealed that this specific subset of Tang cells exhibited senescent profile and has low hTERT expression. CD28nullCD4+ Tang cells produced high levels of inflammatory cytokines, IL-6, IFN-γ and TNF-α, and significantly correlated with the systemic inflammation in hypertensive patients with endothelial dysfunction.Conclusion:Collectively, our findings demonstrate for the first time that CD28null subset in CD4+ Tang cells with senescent and pro-inflammatory phenotype is dependently correlated with impaired FMD and systemic inflammation, which might contribute to the immunopathologic mechanism of endothelial dysfunction. Identification of a pathogenic CD4+ Tang-cell subset lacking CD28 may offer opportunities for the evaluation and management of endothelial dysfunction in hypertension.

Возможности двойной блокады РААС в коррекции эндотелиальной дисфункции у больных артериальной гипертензией: сравнительное исследование

Возможности двойной блокады РААС в коррекции эндотелиальной дисфункции у больных артериальной гипертензией: сравнительное исследование

P5456The role of ST2 as an early marker of endothelial dysfunction in hypertensive patients

Abstract Background The association between endotelial dysfunction and progression of diastolic dysfunction suggests that endotelial and myocardial impairment might have similar pathogenic pathways. Moreover, in hypertensive diabetics the endotelial function is worse in those with impaired diastolic performance compared to normal diastolic performance. ST2 provides additional data to echocardiography in early detection of diastolic performance alteration in hypertension (HT) and is a prominent predictive marker of worse clinical outcome in hypertensive patients. There is scarce data on ST2 role in detection of early vascular involvement in hypertensive patients. Purpose The aim of the study is to evaluate whether ST2 levels correlate with impaired endotelial function in hypertensive patients. Methods Our prospective study included 84 hypertensive patients (mean age 52.9±14.4 yrs, 54.3% males and 45.7% females), after they signed an informed consent. All patients underwent clinical and laboratory (including ST2) evaluation. To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter both at rest and during reactive hyperemia in the muscle distal to the brachial artery (BA) which causes endothelium-dependent vasodilatation. The study methodology was approved by the Ethical Committee and statistical data processing was performed with SPSS. Results Patients were assigned to group A – those without left ventricular hypertrophy (LVH) and group B – those with LVH. There were no significant differences regarding gender, age and HT stage between groups A and B. Patients in group A had lower ST2 levels [18.83 (13.98 - 42.05) vs 55.63 (48.6 - 100.21) vs, p&lt;0.001] and fewer risk factors (1.4 vs 2.6, p&lt;0.01) compared to group B. We found significant differences regarding diastolic performance parameters between the groups. The relative increase in diameter (% FMD; DD = D 100) was significantly higher in group A than group B (6.67±0.43% vs 3.10±0.33%, p&lt;0.01). ST2 levels were greater in group B and correlated with the degree of endotelial dysfunction evaluated by flow-mediated dilatation (FMD) (r=0.411, p&lt;0.01). Multiple regression analysis showed that ST2 had a significant negative correlation with the relative increase in arterial diameter while multivariate Cox regression analysis showed ST2 was an independent predictor of endothelial dysfunction severity in hypertensive patients (hazard ratio: 4.012, 95% confidence interval: 1.207–31.24, P=0.031). Conclusions ST2 levels correlate with cardiovascular risk and are a significant predictive marker of endothelial dysfunction in hypertensive patients regardless of diastolic dysfunction.

Endothelin-1 is a surrogate biomarker link severe periodontitis and endothelial dysfunction in hypertensive patients: The potential nexus

Aim and Objectives: The objective of this study was to illustrate the link between periodontitis (PO) and endothelial dysfunction in hypertensive patients. Materials and Methods: This cross-sectional study involved 53 hypertensive patients with or without PO compared with 28 healthy controls. On the basis of the study protocol, the participants were divided into three groups: Group (1): 24 patients with hypertension only, Group (2): 29 patients with hypertension and PO, and Group (3): 28 healthy controls. Lipid profile, endothelin-1 (ET-1), and high-sensitivity C-reactive protein (hs-CRP) were measured. Blood pressure and body mass index (BMI) were evaluated. Diagnostic criteria of severe PO periodontal indices including plaque index, gingival index, and community periodontal index were estimated. Data collected during the study were analyzed using analysis of variance followed by Bonferroni post hoc test and unpaired t-test (IBM SPSS Statistics for Windows, version 20.0, 2014, IBM, Armonk, NY). Results: BMI was not differed in both groups, P = 0.08. Systolic blood pressure and diastolic blood pressure were high in hypertensive patients with PO compared with hypertensive patients only, P = 0.04 and P = 0.03, respectively. Moreover, hypertensive patients with PO showed significant dyslipidemic status compared with hypertensive patients only (P < 0.05). Biomarker of endothelial dysfunction (ET-1) was elevated in patients with PO (67.54 ± 13.56 pg/mL) compared with hypertensive patients only (23.67 ± 9.63 pg/mL), P = 0.0001. hs-CRP serum level was increased patients with PO compared with hypertensive patients only, P = 0.002. PO indices were high in patients with PO compared with hypertensive patients only, P < 0.01. Conclusion: ET-1 serum level is elevated in hypertensive patients with severe PO and correlated with cardio-metabolic complications, mainly endothelial dysfunction. Therefore, ET-1 serum level is regarded as a surrogate biomarker link PO with risk of endothelial dysfunction.

Особенности дисфункции эндотелия у больных артериальной гипертензией с добавочными почечными артериями

Особенности дисфункции эндотелия у больных артериальной гипертензией с добавочными почечными артериями

Performing under pressure: hypertension and the regulation of cerebral oxygen delivery.

Performing under pressure: hypertension and the regulation of cerebral oxygen delivery.

Correlation between Flicker-Induced Retinal Vessel Vasodilatation and Plasma Biomarkers of Endothelial Dysfunction in Hypertensive Patients

ABSTRACTPurpose: Hypertension (HT) strongly affects the vascular endothelium, resulting in chronic inflammatory disease. Dynamic vessel analysis (DVA) is a modern methodological approach to analyze vascular function in the retinal microcirculation. The aim of this study was to examine whether a defective retinal vessels response is associated with HT-induced endothelial dysfunction.Materials and Methods: Retinal vessel reactions to flicker stimulation were examined by DVA in both eyes of 37 hypertensive and 41 healthy control subjects. Plasma concentrations of C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNFɑ) were measured using the enzyme-linked immunosorbent assay.Results: Both arterial and vein responses to flicker stimulation were significantly decreased in patients with HT compared with the healthy controls (dilatation of the arteries was lower in the HT group by, on average, 1.31, p = 0.001 and dilatation of the veins was lower in the HT group by, on average, 1.32, p = 0.002) after independent adjustment for age, sex, body mass index, and pressure values. In the hypertensive group, there was a negative correlation between the arterial response to flicker stimulation and the plasma CRP concentration (Spearman’s Rank-order Coefficient (Rs) = −0.29, p = 0.07). Similarly, the plasma TNFα concentrations negatively correlated with the arterial response to flicker stimulation (Rs = −0.39, p = 0.02).Conclusions: Our results indicate that DVA directly reflects the actual metabolic status of the retinal endothelium. DVA might be used as an early noninvasive screening tool to detect vascular dysregulation and pan-endothelial dysfunction in patients with HT.

The GG genotype of the -152 G/A vascular endothelial growth factor (VEGF) polymorphism predisposes to hypertension-related chronic kidney disease.

Our purpose was to determine whether the VEGF -152 G/A polymorphism could be associated with chronic kidney disease and endothelial dysfunction in hypertensive patients. There were 100 healthy volunteers enrolled into the control group. The group of patients was constituted by 99 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. All patients were treated with anti-hypertensive polytherapy. Presented study revealed that the hypertensive patients bearing the GG genotype were characterized by the highest values of diastolic blood pressure and markers of endothelial damage such as Angiogenin, Endostatin, CRP as well as von Willebrandt factor. In addition, higher number of immature endothelial progenitor cells with CD34(+)CD133(+), CD34(+)CD133(-) markers was observed in GG hypertensive carriers while in normotensive individuals no differences were found. Such phenomenon may indicate an increased mobilization of bone-marrow derived endothelial progenitors. It may testify to the preserved compensatory mechanism in chronic kidney disease (CKD) patients until the G3a stage of the disease. Moreover, patients with higher estimated glomerular filtration rate (eGFR) level had lower of vWf and Endostatin values, and higher level of VEGF. Taken together our findings clearly indicate the -152 GG hypertensive carriers as more prone to develop CKD. We can suspect that the VEGF -152 GG genotype is strongly associated with hypertension-dependent CKD.

Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β‐Blockers?

We have read with great interest the recently published article by Neuman and coworkers1 in which they hypothesized that nebivolol, a selective β1-antagonist that stimulates nitric oxide (NO), improves endothelial function in African Americans with hypertension when compared with metoprolol. In that well-designed study, the authors found evidence for NO bioavailability at rest during treatment with both nebivolol and metoprolol succinate in hypertensive African American patients, with a clear trend for a greater contribution of NO during nebivolol therapy. Moreover, after combined blockade of NO and endothelium-derived hyperpolarizing factor (EDHF), there was significantly greater vasoconstriction during nebivolol compared with metoprolol therapy, suggesting a greater contribution of both NO and EDHF combined to resting vasomotor tone during nebivolol treatment. Moreover, the contribution of NO to exercise-induced vasodilation was greater during treatment with nebivolol compared with metoprolol succinate. Nebivolol is a third-generation, β1-adrenergic receptor antagonist that has vasodilatory properties both in animals and humans independent of β1-receptor antagonism and related to β3-receptor agonist effects.2-5 It is a racemic mixture of D- and L-enantiomers, of which D-nebivolol is considered to be a highly selective β-adrenergic receptor antagonist.5-8 It was demonstrated that nebivolol stimulates NO release through both β3-receptor and adenosine triphosphate–dependent, P2Y-receptor activation.3, 9-12 In a well-designed clinical study, Tzemos and coworkers13 analyzed whether nebivolol could improve endothelial dysfunction in patients with essential hypertension. They showed that nebivolol/bendrofluazide increased both stimulated and basal endothelial NO release, whereas, for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on NO bioactivity; therefore, they concluded that nebivolol may offer additional vascular protection in treating hypertension.13 Moreover, Oelze and coworkers14 demonstrated that nebivolol but not metoprolol improved endothelial function and reduced vascular oxidative stress in an experimental model of AngII-induced hypertension. These effects were associated with a normalization of the expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits Nox1, Nox2, p22phox, p47phox, p67phox, and Rac1 and an inhibition of NOS III uncoupling in a rat hypertension model. More importantly, they found that nebivolol but not metoprolol inhibited activation of vascular NADPH oxidase and were able to dissociate an already assembled and active membrane-associated NADPH oxidase complex. These observations indicate that nebivolol, in addition to its β1-receptor–blocking and NO-releasing effects, possesses substantial inhibitory effects on vascular oxidative stress, all of which may beneficially influence endothelial dysfunction because of oxidative stress in the setting of arterial hypertension.14 It is well-known that essential hypertension is associated with endothelial dysfunction, and with greater oxidative stress producing free oxygen radicals that contribute to the decrease in NO bioavailibility. Elevated plasma levels of malondialdehyde, a final product of lipid peroxidation and an index of oxidative stress, have been demonstrated in patients with essential hypertension.15, 16 Concordantly, our study group previously found that nebivolol, differently from metoprolol, improved oxidative stress and insulin sensitivity, decreased plasma sP-selectin, and increased adiponectin levels in hypertensive patients.17 From that standpoint, we concluded that nebivolol may significantly improve endothelial dysfunction in hypertensive patients. However, our study population had no African American patients, unlike the patient population from the study by Neumann and coworkers. In conclusion, nebivolol has beneficial effects on endothelial function mainly by increasing NO bioavailability. We strongly believe that although standard β-blockers are falling out of favor nowadays, perhaps the new generation of β-blockers such as nebivolol may “rescue” the reputation of these agents in the near future. There are no conflicts of interest to declare.

Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome-Related Endothelial Dysfunction in Hypertensive Patients.

Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS−NAFLD− and MS+NAFLD−. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD− and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD−, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.

Serum phosphorus levels are associated with endothelial dysfunction in hypertensive patients

Background and aimsRecent data demonstrated that serum phosphorus, within the normal range, is an independent predictor of atherosclerotic cardiovascular disease, independently of renal function. Traditional cardiovascular risk factors are important mediators of endothelial dysfunction, the early step of atherosclerosis. We designed this study to evaluate a possible correlation between serum phosphorus and endothelium-dependent vasodilation, evaluated by the strain-gauge plethysmography, in naïve hypertensives. Methods and resultsWe investigated by strain-gauge plethysmography, the relationship between forearm blood flow (FBF) response to acetylcholine (ACh) and serum phosphorus in 500 patients with uncomplicated, never-treated, essential hypertension, divided by phosphorus tertiles. There were no significant differences among tertiles with the exclusion of forearm blood flow (FBF). Phosphorus (β = −0.454; P = 0.0001), estimated-glomerular filtration rate (e-GFR, by CKD-EPI formula) (β = 0.261; P = 0.0001), gender (β = 0.215; P = 0.0001), BMI (β = −0.086; P = 0.018), HDL-cholesterol (β = 0.077; P = 0.036) were significantly related to endothelium-dependent vasodilation. In an additional analysis including serum high sensitivity C-reactive protein (hs-CRP) (measured in 400 patients) in the same model, the link between serum phosphorus and ACh-stimulated FBF did not change (β = −0.422; P = 0.0001). Clinically relevant, 0.1 mg of phosphorus increase is associated with a reduction of 22% of ACh-stimulated FBF. On multiple logistic regression analysis, the risk of endothelial dysfunction was about twice higher in patients in the second (OR = 1.754, 95% CI = 1.055–2.915; P = 0.030) and three-fold higher in the third tertile (OR = 2.939, 95% CI = 1.598–5.408; P = 0.0001) in comparison with those in the first tertile of phosphorus. ConclusionAn impaired ACh-stimulated FBF is associated with serum phosphorus levels, within the normal range, in hypertensives.

Impact of psychoemotional stress and physical activity on endothelial function in hypertensive patients with obesity

Objective . To study the effect of chronic emotional stress and physical activity on endothelial function in patients with arterial hypertension (HTN) and obesity. Design and methods. We enrolled 76 male patients with HTN stage I and II. Group 1 consisted of 36 patients with HTN and obesity, group 2–40 hypertensive patients without obesity. Ultrasound of the brachial artery was performed to assess endothelial function after reactive hyperemia (flow-mediated dilation) and nitrate administration (nitrate-mediated dilation). Serum cortisol level was determined by enzyme-linked immunosorbent assay. PSM‑25 scale was used to access psycho-emotional stress. The level of reactive and personal anxiety was measured by the Spielberger and Khanin’s questionnaire. Brief international physical activity questionnaire was used (IPAQ) for physical activity evaluation. Results. In patients with HTN and obesity a more significant deterioration of the flow-mediated and nitrate-mediated dilation (FMD and NMD) was found compared to hypertensive patients without obesity, and to healthy individuals. In both groups physically inactive patients showed a significant decrease in endothelial function compared to physically active patients. In group 1, an inverse correlation between FMD with the level of reactive anxiety and trait anxiety (r = –0,54; r = –0,46, respectively; p < 0,05) and a direct correlation with the level of physical activity (r = 0,42; p = 0,01) was found. In group 2, FMD and NMD inversely correlated with psycho-emotional stress (r = –0,42; r = –0,33, respectively; p < 0,05) and directly correlated with the level of physical activity (r = 0,46; r = 0,33, respectively; p < 0,05). In both groups, there were direct correlations between cortisol levels with personal and reactive anxiety scores. Furthermore, there was an inverse association between FMD and cortisol levels in group 1 (r = –0,36; p = 0,05) and group 2 (r = –0,41; p = 0,02). Conclusions. Our findings suggest a strong connection between chronic emotional stress and physical inactivity with endothelial dysfunction in hypertensive patients.

Screening the markers of endothelial dysfunction in hypertensive patients with obesity

Screening the markers of endothelial dysfunction in hypertensive patients with obesity

Deficiency of the T‐type Calcium Channel Ca v 3.1 Attenuates Endothelial Dysfunction in Aging Mice

Background T-type calcium channels are involved in vasoconstriction. Furthermore, these channels play a larger role in contraction of vascular smooth muscle under increased oxidative stress. It was therefore hypothesized that T-type channels contribute to the endothelial dysfunction during old age. Method: The endothelial function was tested in young and one year old Wt and Cav3.1-/- mice. Mesenteric blood vessels were perfused and changes in luminal diameter were determined. Aortae were isolated, suspended in a wire-myograph and changes in tension were determined. Results: Depolarization by high K+ induced a constriction followed by secondary dilatation (recovery) in mesenteric vessels. The recovery was significantly diminished in Wt mice with age. By contrast, recovery was significantly increased with age in KO mice. Pretreatment with L-NAME abolished recovery. The initial constriction was not different between Wt and KO mice. Aortae were precontracted by high K+(EC70) with no difference between young and old mice. Acetylcholine-induced relaxations in aortae were significantly smaller (abolished) in old compared to young Wt mice. By contrast, there was no difference in the aortic response to acetylcholine between old and young KO mice. Conclusion T-type calcium channel deficient mice are protected against age-dependent endothelial dysfunction as arteries of T-type deficient mice do not develop decreased recovery and reduced responses to acetylcholine with age. This is in line with studies suggesting that T-type blockers have a protective effect against endothelial dysfunction in hypertensive patients. Foundation: Danish Research Council and Danish Heart Foundation.