Resistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity. Low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated with RHTN. Single nucleotide polymorphisms (SNPs) -11377C/G (rs266729) and +276G/T (rs1501299) in ADIPOQ (adiponectin gene) were associated with hypertension. This study evaluated the association between two SNPs (-11377C/G and +276G/T) and adiponectin levels in RHTN. This study comprised 109 patients with RHTN genotyped for both polymorphisms. A cross-sectional study was designed to compare features of CC homozygous versus G allele carriers for -11377C/G and GG homozygous versus T allele carriers for +276G/T. Office and ambulatory BP measurements were similar among genotypes subgroups in both SNPs as well as the markers of target organ damage (arterial stiffness, left ventricular mass index and microalbuminuria). Adiponectin concentrations were significantly higher in CC compared to G carrier for -11377C/G (CC:7.0 (4.0-10.2) versus G allele:5.5 (2.5-7.9), p = 0.04) and lower in GG compared to T carrier for +276G/T (GG:5.3 (2.3-7.7) versus T allele:7.1 (3.6-10.5), p = 0.04). Adjusting for systolic ambulatory BP, body mass index, age, gender, race and presence of type 2 diabetes, multiple linear regression analyses revealed that the minor alleles G (β-coefficient= -0.14, SE=0.07, p = 0.03) and T (β-coefficient=0.12, SE=0.06, p = 0.04) were independent predictors of adiponectin. The -11377C/G and +276G/T SNPs in ADIPOQ were associated with adiponectin levels in RHTN individuals.
Resistant hypertension (RHTN) and target organ damage are linked to increased inflammatory biomarkers, which may regulate adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1); and the platelet (P-selectin) and endothelial (E-selectin) selectins. We investigated a previously unknown relationship between soluble P-selectin (sP-selectin), E-selectin (sE-selectin), ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) with RHTN and target organ damage.We included 110 subjects diagnosed for true RHTN and 112 mild-moderate hypertensive (HTN) patients. Blood pressure parameters, pulse wave velocity and left ventricular mass index (LVMI) were measured. Adhesion molecules were measured on ELISA. Both sP-selectin and sE-selectin were increased; in contrast, sICAM-1 was reduced in RHTN compared with HTN patients, while similar sVCAM-1 was noted in the groups. sP-selectin and sVCAM-1 were elevated in the presence of arterial stiffness (sP-selectin: 104±47 vs. 89±45 ng/ml, P<0.05; sVCAM-1: 1,189±411 vs. 1,060±412 ng/ml, P<0.05) and cardiac hypertrophy (sP-selectin: 105±51 vs. 88±43 ng/ml, P<0.05; sVCAM-1: 1,170±433 vs. 1,040±383 ng/ml, P<0.05) in all HTN patients. sP-selectin was associated with target organ damage after adjustment for age and BP. Apart from potential confounders, sE-selectin was a significant indicator of RHTN.The adhesion molecule sP-selectin plays a role in cardiovascular damage, and sE-selectin in resistance to antihypertensive therapy. (Circ J 2016; 80: 1196-1201).
Objective: The purpose of this study was to evaluate the prevalence of metabolic syndrome (MetS) and the clinical features associated with it in resistant and mild to moderate hypertensives.Methods: This cross-sectional study included 236 patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients with resistant hypertension (RHTN).We determined blood pressure measurements and adipokines levels.Target organ damages such as microalbuminuria (MA), cardiac hypertrophy and arterial stiffness were also assessed.Results: We found a prevalence of 73% in resistant and 60% in mild-to-moderate hypertensive patients.The patients with MetS showed a higher prevalence of MA ≥30mg.g⁻¹compared to their counterparts (20% vs. 4%).Adiponectin levels were significantly lower in patients with MetS (5.30 vs. 7.50 µg.mL⁻¹), while leptin demonstrated to be increased in those patients, compared to the subjects without MetS (21.0 vs. 15.7 ng.mL⁻¹).Finally, in a multiple regression analysis MA (OR=8.51;p=0.01), leptin/adiponectin ratio (LAR) (OR=4.13;p=0.01) and RHTN (OR=3.75;p=0.03) were independently associated with the presence of MetS, apart from potential confounders.Conclusions: Our findings suggest that the metabolic derangements present in MetS tend to develop early signs of end-organ damage with hormonal changes in hypertensive patients.Indeed, LAR may be useful as a reliable biomarker for identifying those who are at risk for developing MetS.
Introduction: Endothelial function, intima-media thickness (IMT) and vascular stiffness are variables closely associated in normotensive subjects as well as in hypertensive and diabetic (DM) patients; however this correlation has not been tested in resistant hypertensive (RHTN) individuals. It is known that DM is a very common finding in RHTN, but it is controversial whether this condition causes some incremental impairment in vascular dysfunction in these patients. Also, it is controversial if glycated haemoglobin plasma levels predict arterial abnormalities in RHTN individuals. Methods: Two hundred and six RHTN patients were divided in two groups: RHTN+DM (HBglic=7.3%, age= 58.7y, BMI= 30.8, n= 134) and RHTN-nonDM (5.5%, age= 58.3y, BMI= 30.5, n=72). Blood pressure (ABPM and office) was similar between the 2 groups (RHTN+DM= 150/87/63 and RHTN-nonDM= 151/89/62 mmHg; p> 0.05). Arterial rigidity (PWV, m/s, Sphygmocor system), endothelial function (FMD,%) and carotid IMT (mm) were assessed and parametric tests (t Student, Pearson correlation and linear regression) used analyse the data. Results (mean±SD): RHTN-DM group had higher values of PWV (12.1±1.6 vs. 10.7±1.7 m/s; p< 0.001) and lower measurements of FMD (7.3±1.8 vs. 8.2±1.9%; p<0.001); however, IMT values were found similar in the 2 groups (1.02±0.2 vs. 1.01±0.2 mm; p= 0.77). Hbglyc levels correlated with PWV (R=0.31; p<0.001) and FMD (R=-0,52; p<0,0001) only in the RHTN-DM group (RHTN-nonDM: R=0.01, p= 0.93, and R=-0.03, p=0.79, respectively). Linear regression analysis showed statistical significance between HbGlyc and PWV and e FMD only in RHTN-DM patients (p<0.05). Conclusion: DM worsened endothelial dysfunction and vascular stiffness, but not IMT, in RHTN subjects. Glycated haemoglobin is an important predictor of arterial rigidity and endothelial function in diabetic RHTN subjects.
Background and Purpose Adenosine is a local mediator that regulates physiological and pathological processes via activation of four GPCRs (A 1 , A 2A , A 2B , and A 3 ). We have investigated the effect of two A 1 ‐receptor‐selective agonists and the novel A 1 ‐receptor bitopic ligand VCP746 on the rat cardiovascular system. Experimental Approach The regional haemodynamic responses of these agonist was investigated in conscious rats. Male Sprague–Dawley rats (350–450 g) were chronically implanted with pulsed Doppler flow probes on the renal, mesenteric arteries and the descending abdominal aorta and the jugular vein and caudal artery catheterized. Cardiovascular responses were measured following intravenous infusion (3 min each dose) of CCPA (120, 400, and 1,200 ng·kg −1 ·min −1 ), capadenoson or adenosine (30, 100, and 300 μg·kg −1 ·min −1 ), or VCP746 (6, 20, and 60 μg·kg −1 ·min −1 ) following pre‐dosing with DPCPX (0.1 mg·kg −1 , i.v.) or vehicle. Key Results CCPA produced a significant A 1 ‐receptor‐mediated decrease in heart rate that was accompanied by vasoconstrictions in the renal and mesenteric vascular beds but an increase in hindquarters vascular conductance. The partial agonist capadenoson also produced an A 1 ‐receptor‐mediated bradycardia. In contrast, VCP746 produced increases in heart rate and renal and mesenteric vascular conductance that were not mediated by A 1 ‐receptors. In vitro studies confirmed that VCP746 had potent agonist activity at both A 2A ‐ and A 2B ‐receptors. Conclusions and Implications These results suggest VCP746 mediates its cardiovascular effects via activation of A 2 rather than A 1 adenosine receptors. This has implications for the design of future bitopic ligands that incorporate A 1 allosteric ligand moieties.
showing that the frequency of patients with true RHT is lower (3.0-4.5% of the general hypertensive population) in clinical settings when compared to 14.5% estimated in the Spanish ABPM Registry
Objective: Resistant hypertensive patients (RHTN) have unfavorable prognosis due to poor blood pressure (BP) control and higher prevalence of target organ damage. Deregulation of matrix metalloproteinases (MMPs) and their inhibitors are related to cardiac remodeling and left ventricular geometry in cardiac diseases.This study aimed to investigate the association between MMP-9 and TIMP-1 levels and the presence of LVH as well as compare its levels between resistant hypertensive patients (RHTN) and mild to moderate hypertensive (HTN). Design and method: This cross-sectional study was performed in the Outpatient Resistant Hypertension Clinic at the Hospital of the University of Campinas. Seventy nine patients classified as resistant hypertensive and 116 mild to moderate hypertensive patients (HTN) were included. Left ventricular mass index (LVMI) was calculated by dividing the LV mass by the body surface area. Plasma levels of MMP-9 and TIMP-1 were determined by ELISA. Results: Higher levels of TIMP-1 (median[IQR]) were found in RHTN RHTN (88.2 [77.4- 100.8]) ng/mL), compared with HTN individuals (79.7 [67.5- 99.6] p = 0.015), while lower levels of MMP-9 9 (23.9 [19.8 -54.2] vs. 38.1 [24.8 -64.0], p = 0.003) and consequently, decreased MMP-9/TIMP-1 ratio were observed in RHTN group (0.30 [0.20–0.56] vs. 0.53 [0.33- 0.85], p < 0.0001). Different patterns of correlation were observed of TIMP-1 with LVMI in the subgroups; in controlled hypertensive patients, a positive correlation was observed (r = 0.25, p = 0.003) whereas in RHTN, TIMP- 1 levels were inversely correlated with LVMI (r = -0.33 p = 0.02). Interestingly, multiple regression analysis showed that TIMP-1 levels are independent predictors for LVMI in RHTN but not in HTN subgroup. Conclusions: Our data suggest that MMP-9/TIMP-1 balance varies according to the severity of hypertension and are associated with resistant hypertension and left ventricular hypertrophy.
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