Thomas K. Schwarz

Renal resistive index in addition to low-grade albuminuria complements screening for target organ damage in therapy-resistant hypertension.

Objective We examined the value of renal resistive index (RRI) for prevalence of cardiovascular target organ damage in therapy-resistant hypertension in comparison to low-grade albuminuria. Methods Eighty-four patients with therapy-resistant hypertension (age 59.7 ± 8.1 years) were screened for cardiovascular target organ damage with coronary computed tomography, cardiac magnetic resonance imaging (MRI), Doppler sonography for the assessment of carotid intima media thickness and, RRI, pulse wave velocity and for low-grade albuminuria of at least 10 mg/day in men and 15 mg/day in women, respectively. Results In patients with RRI greater than 0.7 pulse wave velocity (11.6 ± 3.7 vs. 9.8 ± 2.2 m/s; P = 0.02) intima media thickness (0.85 ± 0.09 vs. 0.76 ± 0.1 mm; P = 0.007) and Agatston score of coronary calcification (640 ± 915 vs. 129 ± 256; P = 0.05) were increased, whereas left ventricular mass (127 ± 24.5 vs. 125 ± 15.0 g; P = 0.70) was similar between the two groups. When patients were categorized according to low-grade albuminuria left ventricular mass was significantly higher in those with low-grade albuminuria (123 ± 25.8 vs. 135 ± 15.7 g; P = 0.01), whereas vascular parameters (intima media thickness, Agatston score, pulse wave velocity) did not differ between the two groups. Conclusion In patients with therapy-resistant hypertension RRI reflects functional and structural vascular parameters, whereas low-grade albuminuria is related to cardiac structural changes. Thus, measurement of RRI in addition to low-grade albuminuria complements screening for target organ damage in therapy-resistant hypertension.

High sodium intake modulates left ventricular mass in patients with G expression of +1675 G/A angiotensin II receptor type 2 gene.

Objectives In patients with hypertension left ventricular hypertrophy (LVH) is associated with genetic variations of the angiotensin type 2 receptor (AT2R). Hypertension and LVH are often aggravated by salt intake. Our objective was to assess the relationship between AT2R gene variation and salt intake and their impact on left ventricular mass (LVM). Methods and results In 205 subjects with normal or mildly elevated blood pressure, we assessed sodium intake and left ventricular structure and function by echocardiography. Intronic +1675 G/A polymorphism of the AT2R gene was investigated. A-allele carriers had a greater LVM (P = 0.049) than G-allele carriers. Independent of diet, septal wall thickness was higher in A-allele carriers (P = 0.001). Fractional fibre shortening was greater in A-allele carriers (P = 0.034), and the velocity of circumferential fibre shortening tended to be greater in A-allele carriers (P = 0.057). When the two groups were stratified according to their salt intake, only G-allele carriers displayed a modulating effect of salt intake on LVM. Covariance analysis revealed that there was a trend towards a modulating effect of salt intake on LVM, even after taking blood pressure into account (P = 0.054). Conclusion Our data clearly support the notion that LVM is influenced by AT2R polymorphisms. Furthermore, G-allele carriers in particular appear to be susceptible to a modifying effect of increased salt intake on LVM.

Renal resistive index—a valid tool to assess renal endothelial function in humans?

BACKGROUND In humans, renal endothelial function is assessed by the vasoconstrictive response to L-NG-monomethyl arginine (L-NMMA). We hypothesized that Doppler sonographic measurements of the renal resistive index in response to inhibition of nitric oxide synthase offer a new methodological approach for testing renal endothelial function. METHODS Forty-one patients without nephropathy were included. Para-aminohippurate and inulin clearance were performed under basal conditions and during L-NMMA infusion. In parallel, renal resistive index was assessed by Doppler sonography, and central blood pressure was determined. RESULTS Following nitric oxide synthase inhibition, renal resistive index increased significantly, and 29% of our patients developed Doppler sonographic diastolic zero flow. Renal plasma flow decreased in response to L-NMMA, and conversely, renal vascular resistance increased. There was no correlation of renal vascular resistance and renal resistive index at baseline and during nitric oxide synthase inhibition. Changes in renal resistive index were not related to changes in renal perfusion or renal vascular resistance. Renal resistive index correlated with central pulse pressure at baseline and during L-NMMA infusion, whereas renal vascular resistance did not correlate with central pulse pressure. CONCLUSION Our data do not support the hypothesis that renal resistive index is a tool to test renal endothelial function in humans and should not be used interchangeably with renal vascular resistance.

Valsartan and retinal endothelial function in elderly hypertensive patients

Background. The aim of this study was to investigate the impact of short‐term treatment with the angiotensin II receptor blocker (ARB) valsartan on retinal endothelial function in elderly patients with mild to moderate essential hypertension. Methods. In an open‐labeled study, 20 elderly, male patients with arterial hypertension (WHO I–II) were treated with the ARB valsartan (80–160 mg once daily) over 8 days. Central retinal artery perfusion at rest and during flicker light stimulation was measured before and after treatment using pulsed wave Doppler sonography. Retinal capillary flow was assessed with scanning laser Doppler flowmetry at rest and following systemic infusion of the nitric oxide synthase (NOS) inhibitor NG‐monomethyl‐l‐arginine (L‐NMMA). Results. While valsartan significantly lowered blood pressure, central retinal artery perfusion at rest as well as after flicker light stimulation was similar before and after treatment. Similarly, retinal capillary flow at rest and after infusion of L‐NMMA did not change with valsartan after 7 days of treatment. Subgroup analysis revealed that changes in retinal capillary flow in response to L‐NMMA might be dependent on serum low‐density lipoprotein (LDL) cholesterol levels of study participants. After treatment with valsartan, retinal capillary flow in response to L‐NMMA decreased more in patients with low (<3.54 mmol/l) than with high LDL‐cholesterol levels (−12.6±20.2% vs 12.3±19.5%, p<0.05). Conclusion. Short‐term treatment with valsartan did not improve retinal endothelial function in elderly hypertensive patients.

Low dose-eplerenone treatment decreases aortic stiffness in patients with resistant hypertension

Vascular damage is aggravated in animal models of hypertension with mineralocorticoid (MR) excess and in hypertensive patients with primary hyperaldosteronism. MR antagonism has shown to provide effective blood pressure (BP)‐control in patients with treatment resistant hypertension (TRH), but the concurrent effects on the vasculature have not been examined. In a randomized, double‐blinded, placebo‐controlled parallel‐group study, 51 patients with TRH received either eplerenone 50 mg or placebo for 6 months together with additional antihypertensives titrated to achieve a BP target of <140/90 mm Hg. Pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), AP normalized to a heart rate of 75/min (AP@HR75), renal resistive index (RRI), intima‐media thickness (IMT) and urinary albumin excretion rate (UAER) were assessed before and after treatment. PWV was reduced only with eplerenone (from 11.3±3.6 to 9.8±2.6 m/s, P˂.001), but not with placebo (10.3±2.0 to 10.1±1.8 m/s, P=.60), despite similar reductions in BP (−35±20/−15±11 mm Hg vs −30±19/−13±7 mm Hg, n.s.). Further, reductions in AP and AP@HR75 were greater with eplerenone, while changes in AIx, RRI, IMT and UAER were similar. Our data show that eplerenone beneficially affects markers of arterial stiffness and wave reflection in patients with TRH, independently of BP lowering. These data add to the evidence that MR antagonism should be the preferred treatment option in TRH.