The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension : a cross-sectional study

Background: Obesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients. Methods: The 541 participants (20–72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability. Results: Mean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p < 0.05 for all). Cardiac index was lower in quartile 4 versus quartile 1, while no differences were seen in heart rate variability, augmentation index, plasma renin activity, and aldosterone concentration between the quartiles. Linear regression analyses showed independent associations of abdominal obesity with higher aortic systolic and diastolic blood pressure, systemic vascular resistance, and pulse wave velocity (p < 0.05 for waist:height ratio in all regression models). Conclusion: Higher waist:height ratio was associated with elevated blood pressure, systemic vascular resistance, and arterial stiffness, but not with alterations in cardiac sympathovagal modulation or activation of the circulating renin-angiotensin-aldosterone system. Although obesity-related elevation of blood pressure has distinct phenotypic features, these results suggest that its main characteristics correspond those of primary hypertension. Trial registration: ClinicalTrails.gov NCT01742702 (date of registration 5th December 2012).publishedVersionPeer reviewe

LDL cholesterol is associated with systemic vascular resistance and wave reflection in subjects naive to cardiovascular drugs

Background and aim: Low density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerosis, but it is also associated with elevated blood pressure (BP) and future development of hypertension. We examined the relationship between LDL-C and haemodynamic variables in normotensive and never-treated hypertensive subjects. Methods: We recruited 615 volunteers (19–72 years) without lipid-lowering and BP-lowering medication. Supine haemodynamics were recorded using continuous radial pulse wave analysis, whole-body impedance cardiography, and single channel electrocardiogram. The haemodynamic relations of LDL-C were examined using linear regression analyses with age, sex, body mass index (BMI) (or height and weight as appropriate), smoking status, alcohol use, and plasma C-reactive protein, sodium, uric acid, high density lipoprotein cholesterol (HDL-C), triglycerides, estimated glomerular filtration rate, and quantitative insulin sensitivity check index as the other included variables. Results: The mean (SD) characteristics of the subjects were: age 45 (12) years, BMI 27 (4) kg/m2, office BP 141/89 (21/13) mmHg, creatinine 74 (14) µmol/l, total cholesterol 5.2 (1.0), LDL-C 3.1 (0.6), triglycerides 1.2 (0.8), and HDL-C 1.6 (0.4) mmol/l. LDL-C was an independent explanatory factor for aortic systolic and diastolic BP, augmentation index, pulse wave velocity (PWV), and systemic vascular resistance index (p  Conclusions: LDL-C is independently associated with BP via systemic vascular resistance and wave reflection. These results suggest that LDL-C may play a role in the pathogenesis of primary hypertension.</p

Erratum: Vasopeptidase Inhibition Corrects the Structure and Function of the Small Arteries in Experimental Renal Insufficiency

<b><i>Background:</i></b> We studied whether vasopeptidase inhibition corrects the structure and function of the small arteries in experimental chronic renal insufficiency (CRI). <b><i>Methods:</i></b> After 5/6 nephrectomy (NX) surgery was performed on rats, there was a 14-week follow-up, allowing CRI to become established. Omapatrilat (40 mg/kg/day in chow) was then given for 8 weeks, and the small mesenteric arterial rings were investigated in vitro using wire and pressure myographs. <b><i>Results:</i></b> Plasma and ventricular B-type natriuretic peptide (BNP) concentrations were increased 2- to 2.7-fold, while systolic blood pressure (BP) increased by 32 mm Hg after NX. Omapatrilat treatment normalized the BNP and reduced the BP by 45 mm Hg in the NX rats. Endothelium-dependent vasorelaxation was impaired but the response to acetylcholine was normalized after omapatrilat treatment. Vasorelaxations induced by nitroprusside, isoprenaline and levcromakalim were enhanced after omapatrilat, and the responses were even more pronounced than in untreated sham-operated rats. Arterial wall thickness and wall-to-lumen ratio were increased after NX, whereas omapatrilat normalized these structural features and improved the strain-stress relationship in the small arteries; this suggests improved arterial elastic properties. <b><i>Conclusion:</i></b> Omapatrilat treatment reduced BP, normalized volume overload, improved vasorelaxation and corrected the dimensions and passive elastic properties of the small arteries in the NX rats. Therefore, we consider vasopeptidase inhibition to be an effective treatment for CRI-induced changes in the small arteries

Supplementary Material for: Dietary Phosphate Binding and Loading Alter Kidney Angiotensin-Converting Enzyme mRNA and Protein Content in 5/6 Nephrectomized Rats

<i>Background:</i> Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotensin system components in the surgical 5/6 nephrectomy rat model (5/6 NX) of chronic renal insufficiency. We tested the hypothesis whether dietary modification of phosphate influences kidney renin-angiotensin system gene expression at the mRNA level in 5/6 NX rats. <i>Methods:</i> Fifteen weeks after surgery, rats were given control diet (0.3% calcium, 0.5% phosphate), phosphate-lowering diet (3% calcium as carbonate) or high-phosphate diet (1.5%) for 12 weeks. Sham-operated rats were on control diet. <i>Results:</i> Blood pressure, plasma phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were increased in remnant kidney rats, whereas creatinine clearance was decreased. Phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were further elevated by the high-phosphate diet, but were reduced by the phosphate-lowering diet. Plasma calcium was increased with the phosphate-lowering diet and decreased with the high-phosphate diet. Remnant kidney rats on control diet showed upregulated kidney angiotensin-converting enzyme (ACE) and angiotensin (Ang) IV receptor (AT₄) transcription, while ACE2, Ang II type 2 receptor and renin receptor transcription were downregulated in comparison with sham rats. Phosphate-lowering diet reduced whereas high-phosphate diet increased kidney ACE, and these effects were observed at both mRNA and protein levels. Dietary phosphate loading also resulted in lower AT_1a gene transcription. <i>Conclusion:</i> Dietary phosphate loading was associated with elevated kidney ACE expression, increased tissue damage and lower AT_1a transcription in 5/6 NX rats. Phosphate binding with 3% calcium carbonate had opposite effects on ACE and kidney damage