Hypertensive crisis is a common clinical situation that presents a high rate of morbidity and mortality and it is characterized by symptomatic rise of blood pressure (BP), systolic (SBP) ≥ 180 mmHg and/or diastolic (DBP) ≥ 120 mmHg. It is classified as emergency (HE) or hypertensive urgency (HU). There is no description of laboratory findings in patients who present acute BP elevation. Thus, this study had the objective to assess the biochemical-metabolic parameters of patients with HC. We studied 74 normotensive individuals (NT), 74 controlled hypertensive patients (ContrHT), 50 subjects with HU, and 78 with HE for evaluating biochemical-metabolic parameters. HE occurs in older individuals and more frequently in those with known hypertension. More patients with HE had dyslipidemia than those with HU (58% vs. 38%). The diastolic BP and heart rate were higher in the HE group (120 mmHg and 87 bpm) compared to ContrHT (71 mmHg and 71 bpm; p < 0.0001) and NT groups (75 mmHg and 68 bpm; p < 0.0001). Glycemia was higher in HE vs. NT and ContrHT (p < 0.05). HDL cholesterol was lower in HE than NT (p = 0.0088). Potassium was lower in HE vs. NT, ContrHT and HU groups (p < 0.05). Creatinine was higher in the HC group vs. NT and ContrHT (p < 0.05). The GFR was significantly lower in HE group vs. HU, ContrHT and NT (p < 0.001). In conclusion, individuals with HC show biochemical alterations when compared to ContrHT and NT. Acute BP elevations are associated with hyperglycemia, dyslipidemia, and higher potassium and creatinine levels and lower renal function. Abbreviations BMI = body mass index BP = blood pressure CH = hypertensive crisis ContrHT = controlled hypertensive DBP = diastolic blood pressure GFR = glomerular filtration rate HbA1c = glycated hemoglobin HDLc = high-density lipoprotein cholesterol HE = hypertensive emergency HPLC = high-performance liquid chromatography HR = heart rate HU = hypertensive urgency JNC 7 = VII Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure LDLc = low-density lipoprotein cholesterol MDRD = Modification of Diet in Renal Disease NT = normotensive RASB = renin-angiotensin system blockers SBP = systolic blood pressure TC = total cholesterol TG = triglycerides.
Background: Matrix metalloproteinase-9 (MMP-9) participates in the degradation of components of the extracellular matrix and it is involved in vascular remodeling and vasomotor changes. The aim of this study was to investigate the plasma levels of MMP-9 in acute vascular alterations due to hypertensive crisis. Methods: This cross-sectional study was performed in 40 normotensive (NT) and 58 controlled hypertensive subjects (CHyp) followed up in outpatient clinic. Moreover, 57 patients with hypertensive emergency (HypEmerg) and 43 in hypertensive urgency (HypUrg), seen in emergency department, were also included. Hypertensive crisis was divided into HypEmerg, which was characterized by levels of systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥ 120 mmHg complicated with target-organ damage (TOD), and HypUrg, defined by BP elevation without TOD. Univariate and multivariate regression analysis was performed to identify the influence of independent variables on MMP-9 levels. A p-value < 0.05 was considered statistically significant. Results: The mean age was 43.5 years in the NT group (11 men); 57.7 years in the CHyp group (29 men); 59.4 years in the HypUrg group (21 men) and 62.4 years in the HypEmerg group (31 men). The age was statistically different in the NT group compared to other 3 groups. The mean BP was 116.5 ± 13.9/72.4 ± 10.6 mmHg for NT, 123.2 ± 12.6/79 ± 9.2 for CHyp, 194.1 ± 24.3/121.4 ± 17.3 for HypUrg and 191.6 ± 34.3/121.7 ± 18.8 mmHg for HypEmerg, respectively (p-value< 0.0001 between groups). MMP-9 levels were statistically different between the HypEmerg (2.31 ± 0.2 ng/mL) and HypUrg groups (2.17 ± 0.3 ng/mL) compared to the NT (1.94 ± 0.3 ng/mL) (p-value < 0.01 and p-value < 0.05, respectively) and CHyp groups (1.92 ± 0.2 ng/mL) (p-value < 0.01). Uric acid was the only independent variable for predicting MMP-9 levels (p-value = 0.001). Conclusion: MMP-9 concentrations are significantly higher in the hypertensive crisis groups (urgency and emergency) compared to the control groups. Therefore, MMP-9 may be a biomarker or mediator of pathophysiologic pathways in cases of acute elevations of blood pressure.
Background Estrogens have a modulatory effect on several immune responses, many of which are correlated to autoimmune diseases. Estrogens act through binding to their receptors, and an overexpression of these receptors has been identified in patients with different autoimmune diseases. Here we analyzed the association of a putative functional genetic variant in the main estrogen receptor (ERα) gene ( ESR1), and the susceptibility to clinical findings and severity of SLE. Methods A total of 426 individuals (266 healthy controls and 160 SLE patients) were genotyped for the polymorphism rs2234693 in the ESR1 gene. Allele and genotype frequencies were calculated and analyzed between cases and controls using Unphased software. Results The SNP rs2234693 was not associated with SLE per se but the minor allele rs2234693-C was correlated with the presence of nephritis and discoid skin rash. On the other hand, the rs2234693-CC genotype was correlated with the absence of arthritis as well as anti-ANA and anti-RNP autoantibodies. The comprehensive clinical analysis of these patients revealed a more severe status of the disease, characterized by a younger age of onset and higher number of organs involved when compared to European populations. Conclusions Minor allele rs2234693-C was associated with renal and cutaneous involvement, as well as the absence of arthritis, anti-ANA and anti-RNP autoantibodies.
BackgroundResistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals.Methods/designThis is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham).DiscussionIn recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous system inhibition can also be noninvasively achieved by electric current. Therefore, the application of TENS may be a new therapeutic option for treating resistant hypertensive individuals.Trial RegistrationClinical Trials NCT02365974Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1302-8) contains supplementary material, which is available to authorized users.
The pathophysiological mechanism of resistant hypertension (RH) is related to increased vascular smooth muscle tone and blood volume, exacerbation of the activity of the sympathetic system and hyperactivity of the renin-angiotensin-aldosterone system (RAAS), all of which are important regulatory mechanisms of blood pressure. Hypertension is associated with reduced endothelial homeostasis, and thus the best treatment would not only reduce blood pressure but also reverse endothelial injury. RH is associated with more serious vascular dysfunction, assessed by endothelium-dependent vasodilation and the presence of serum biomarkers. Arterial stiffness also constitutes an important independent factor that can determine risk of cardiovascular events in patients with RH; it is an important indicator of vascular changes, and is associated with cardiovascular mortality. Arterial stiffness can be assessed by 3 measures: central blood pressure, augmentation index (AIx) and pulse wave velocity (PWV). PWV is a recognized as main marker of the severity of vascular injury. The increase in central blood pressure caused by backward (reflected) waves can be evaluated as an index derived from an analysis of the central aortic blood pressure curve known as the AIx, and depends on the magnitude and time of the reflected waves and indirectly on heart frequency and arterial stiffness. The evaluation of patients with RH is focused on the identification of causes of hypertension guided by the clinical features of hypertension and metabolic, vascular, endocrine and family history.
Background/Aim: We studied the molecular pathogenesis of obesity, involving complex interactions between environmental and genetic factors, with a focus on the leptin gene. It was our aim to characterize the LEP -2548G>A leptin polymorphism and lipid profile in obese and normal-weight individuals. Methods: A total of 212 individuals were divided into the study group including 136 obese patients (body mass index, BMI ≥30) and the control group with 76 normal-weight individuals (BMI >18.5 and ≤24.9). DNA was amplified by polymerase chain reaction and restriction fragment length polymorphism. The lipid profile was analyzed by enzymatic colorimetric methods. The level of significance was set at p < 0.05. Results: There was a prevalence of the GA genotype in both groups. However, comparative group analysis showed an association of the recessive model (AA+GA) with increased triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) levels in the study group. Conclusion: This study did not confirm an association between obesity and the LEP -2548G>A polymorphism. However, AA+GA genotypes, in the presence of obesity, seem to contribute to a reduction in HDL-C and an increase in TG compared with normal-weight individuals. This should be confirmed in further studies.
IntroductionHypertension and kidney function are closely related. However, there are few studies on renal function during acute elevation of blood pressure (BP), denominated hypertensive crisis (HC).ObjectivesTo evaluate the relationship between renal function and inflammatory cytokines in HC, subdivided into hypertensive urgency (HUrg) and emergency (HEmerg).Materials and methodsThis cross-sectional study was carried out in 74 normotensive (NT) and 74 controlled hypertensive individuals (ContrHT) followed up in outpatient care. Additionally, 78 subjects with hypertensive emergency (HEmerg) and 50 in hypertensive urgency (HUrg), attended in emergency room, were also evaluated. Hypertensive crisis was classified into HEmerg, defined by systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥ 120 mmHg in presence of target-organ damage (TOD), and HypUrg, clinical situation with BP elevation without TOD. The glomerular filtration rate (eGFR) was estimated, and cytokine levels were measured. Statistical analysis was performed using the Kruskal-Wallis or Mann-Whitney test and Spearman’s correlation, with significant differences p-value < 0.05.ResultsThe median age was 53.5 years in the NT group (52 female), 61 years in the ContrHT group (52 female), and 62.5 years in the HC group (63 female) (p-value < 0.0001). The median BP was 118.5/75 mmHg for NT, 113.5/71 for ContrHT, and 198.5/120 mmHg for HC, respectively (p-value < 0.0001 among groups). BP and heart rate levels were significantly higher in the HC group compared to the NT and ContrHT groups (P < 0.001 for all). The eGFR was significantly lower in HC group compared to the NT and ContrHT groups. The cytokine levels were higher in the HEmerg and HUrg groups compared to ContrHT group (P < 0.0001, except for IL-1β in HUrg vs. ContrHT), without difference between the acute elevation of BP groups. Thus, all cytokines were significantly elevated in patients with HC compared to the control groups (NT and ContrHT). There was a negative correlation between eGFR and the cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in the HC group.ConclusionElevated inflammatory cytokines are associated with reduced eGFR in individuals with HC compared to control groups, suggesting that the inflammatory process participates in the pathogenesis of acute elevations of BP.
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