ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

BackgroundThe absence of nocturnal blood pressure dipping (ND) identified by 24-h ambulatory blood pressure monitoring (ABPM) correlates with a worse cardiovascular prognosis. The renin–angiotensin system influences blood pressure levels and the occurrence of target organ damage (TOD). Thus, the aim of this study was to correlate the angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism with the 24-h blood pressure profile and TOD in hypertensive individuals.Methods155 non-diabetic hypertensive individuals on antihypertensive treatment underwent ABPM. Peripheral blood samples were drawn for biochemistry and genetic analysis of the ACE I/D polymorphism by polymerase chain reaction. ND was defined as ≥10 % differences in the mean systolic blood pressure (BP) during wakefulness and sleep.ResultsThere were no differences in clinical or biochemical variables or TOD in respect to ND status, except for higher BP levels during sleep (p < 0.001) in non-dippers. There was significant difference in the prevalence of left ventricular hypertrophy (LVH) between ACE genotypes (II: 13.0 %; ID: 34.1 %; DD: 46.5 %; p value = 0.024) with an increased risk in carriers of the DD genotype (OR = 5.80; IC 95 % 1.50–22.44; p value = 0.011). Carriers of the D allele had higher systolic BP during wakefulness and by ABPM (p < 0.05), higher left ventricular mass (117.3 ± 50.0 vs. 100.3 ± 25.7; p value = 0.017) and higher prevalence of LVH (37.4 vs. 12.5 %; OR = 4.14; 95 % IC: 1.17–14.65; p value = 0.028), compared to the II genotype.ConclusionsThe DD genotype is associated with a higher prevalence of LVH. The presence of the D allele appears to be associated with higher mean 24-h and wake systolic BP measured by ABPM in hypertensive patients under antihypertensive treatment.

BackgroundVildagliptin, a DPP-4 inhibitor widely used for the treatment of type 2 diabetes mellitus (T2DM), shows beneficial effects on endothelial function. This study aims to evaluate the effect of vildagliptin on endothelial function and arterial stiffness in patients with T2DM and hypertension.MethodsFifty over 35-year-old patients with T2DM and hypertension, without cardiovascular disease, will be randomly allocated to two groups: group 1 will receive vildagliptin added-on to metformin and group 2, glibenclamide added-on to metformin. Biochemical tests (glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, alanine aminotransferase, ultrasensitive C-reactive protein, and microalbuminuria), 24-h non-invasive ambulatory blood pressure monitoring, and assessment of endothelial function and arterial stiffness will be performed in both groups before and after 12 weeks of treatment. The endothelial function will be assessed by peripheral arterial tonometry, which measures the reactive hyperemia index (vasodilation), and arterial stiffness will be evaluated by applanation tonometry. All analysis will be performed using SPSS Statistical Software. For all analysis, a 2-sided P < 0.05 will be considered statistically significant.ResultsThe study started in December 2013 and patient recruitment is programed until October 2015. The expected results are that vildagliptin will improve the endothelial function in patients with T2DM and hypertension compared to glibenclamide treatment, independently of glycemic control.ConclusionsIt is expected that this DPP-4 inhibitor will improve endothelial function in patients with T2 DM.Trial registration: Clinical Trials NCT02145611, registered on 11 Jun 2013

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.

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Hypertension and type 2 diabetes mellitus (DM) are among the main risk factors for the development of cardiovascular disease. Pharmacotherapy for DM should not only improve blood glucose control, but also provide beneficial glucose-independent cardiovascular effects. The central systolic blood pressure (SBP) has become more important than the brachial SBP in the assessment of cardiovascular risk.This case report describes the effect of vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on the central SBP in a 54-year-old woman with hypertension and DM. She was submitted to applanation tonometry (AT) before and after vildagliptin association. AT of the radial artery is a non-invasive method that indirectly assesses arterial stiffness by calculating the central SBP and the augmentation index (AIx).After 3 months of follow-up using vildagliptin, central SBP and AIx were improved. Moreover, she presented better glycemic control.This case suggests an effect of DPP-4 inhibitor on arterial stiffness parameter (central SBP) in a hypertensive and diabetic patient, which shows a glucose-independent beneficial cardiovascular effect of this group of drugs.

BackgroundHypertension reduction strategies use blood pressure in the brachial artery as the primary endpoint. Individuals who achieve the target blood pressure reduction with antihypertensive treatment have residual cardiovascular risk attributed to the difference in pressure between the aorta and brachial artery. Antihypertensive treatment affects the intrinsic properties of the vascular wall and arterial stiffness markers and consequently the central pressure. Recent publications stress the importance of adequate control of the central compared to peripheral blood pressure. Related clinical implications suggest that individuals with normal peripheral but high central blood pressure should not receive antihypertensive drugs that act on the central pressure. Therefore, they are at greater cardiovascular risk. The aim of the study was to evaluate the effect of treatment with a thiazide diuretic versus losartan on the central blood pressure in stage 1 hypertensive patients.MethodsTwenty-five patients were randomized to the chlorthalidone 25 mg/amiloride 5 mg group (q.d.) and 25 patients received losartan 50 mg (b.i.d). The central systolic blood pressure (CSBP) and augmentation index (AIx 75) were assessed using applanation tonometry. The paired t-test was used to compare the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), CSBP and AIx 75 between the thiazide and losartan groups at baseline and after 6 months of treatment.ResultsSignificant reductions in CSBP (123.3 ± 14.2 vs. 113.4 ± 111.4, P = 0.0103) and AIx 75 (87.7 ± 9.6 vs. 83.8 ± 8.9, P = 0.0289) were observed after 6 months of drug treatment with chlorthalidone 25 mg/amiloride 5 mg (q.d.). The administration of losartan 50 mg (b.i.d) did not reduce the CSBP and there were insignificant changes in the AIx 75.ConclusionsSix-month treatment of chlorthalidone/amiloride but not losartan reduces the CSBP and AIx 75 in adults with stage 1 hypertension.

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.