Relationship between aortic valve stenosis and the hemodynamic pattern in the renal circulation, and restoration of the flow wave profile after correction of the valvular defect.

OBJECTIVE: The index of maximal systolic acceleration ([AImax]: maximal systolic acceleration of the Doppler waveform divided by peak systolic velocity) shows diagnostic accuracy in screening of renal artery stenosis. This study aimed to determine whether an upstream factor of resistance, such as aortic valve stenosis (AVS), can affect Doppler parameters detected in the peripheral arteries. METHODS: In this prospective study, we measured the AImax in non-stenotic renal interlobar arteries of 62 patients with AVS. Patients were divided into three groups on the basis of severity of valvulopathy as follows: mild-to-moderate AVS (M-AVS; n = 24), intermediate AVS (I-AVS; n = 15), and severe AVS (S-AVS; n = 23) based on Nishimura's criteria. RESULTS: The AImax in the renal parenchymal arteries was significantly lower in the S-AVS group (8.9 ± 3.6 s-1) than in the M-AVS (15.3 ± 3.8 s-1) and I-AVS groups (16.7 ± 5.2 s-1). The AImax was positively correlated with the aortic valve area and inversely correlated with the tranvalvular aortic pressure gradient. After aortic valve replacement, the AImax significantly increased from 10.7 ± 4.0 s-1 at baseline to 19.3 ± 4.4 s-1. CONCLUSIONS: Proximal resistance can lead to diagnostic bias of Doppler parameters that are applied in the diagnosis of peripheral vasculopathies, particularly in renal artery stenosis.

Valvular and/or Non-valvular Aortic Pathology Can Bias the Ultrasonographic Diagnosis of Renal Artery Stenosis.

Renal artery stenosis (RAS) has been shown to cause a reduction in the index of maximal systolic acceleration (AImax: the maximal acceleration of flow waveform in early systole divided by the peak systolic velocity) of blood in the renal interlobar arteries, caused by local dampening of the pulse wave. In previous studies, AImax demonstrated diagnostic accuracy in terms of negative predictive value, which is useful for screening, but had a relatively low specificity. We hypothesized that an upstream focal resistance, such as an aortic stenosis or aneurysm, could act in the same way as RAS, thus generating false positives in non-stenotic kidneys. We studied 226 patients who underwent a complete protocol for RAS screening. AImax was 6.2 ± 2.9 s-1 and 13.4 ± 3.5 s-1 (mean ± standard deviation) in stenotic and non-stenotic kidneys, respectively. Diagnostic accuracy of ultrasonography with respect to the benchmark of renal computed tomography or magnetic resonance angiography (significant RAS cutoff ≥50%) resulted in 97% sensitivity, 94% specificity and a negative and positive predictive value of 99% and 55%, respectively. Using logistic regression for unexpectedly low AImax in non-stenotic kidneys (AImax cutoff ≤ 9.0 s-1), aortic pathology, such as aortic valve stenosis or aortic arch dilation (as assessed by echocardiography), was found to be the only significant predictor (Χ2 = 33.8, p < 0.0001) of false positive cases compared with clinical and hemodynamic variables. We concluded that the aortic valvular and non-valvular pathology can act as a proximal resistance that can attenuate the Doppler flowmetric parameters, which explore the flow waveform in the renal parenchymal arterial circulation, thus mimicking the presence of a focal resistance in the peripheral vascular region explored.

A case report of hyponatremia after surgery for Conn's adenoma.

Primary aldosteronism (PA), also known as Conn's syndrome, is a frequent cause of secondary hypertension. If PA is due to a documented unilateral adrenal adenoma, adrenalectomy is the treatment of choice. Endocrine Society guidelines suggest monitoring potassium after adrenalectomy, while there is no mention of sodium disorders after surgery. Here we report the case of a patient with Conn's syndrome who developed hyponatremia after surgery. This was an unexpected event in the course of the treatment, which sheds light on the fact that low levels of aldosterone strongly influence sodium concentration, and advises clinicians to monitor sodium after adrenalectomy.

Influence of carotid atherosclerotic plaques on pulse wave assessment with arterial tonometry.

OBJECTIVE: Aortic stiffness and central pressure measurements have become increasingly important for the overall estimation of cardiovascular risk. The aim of this study is to verify whether the presence of stenosis in the carotid arteries due to atherosclerotic plaques may induce a bias in the measurement of carotid-femoral pulse wave velocity (PWV) and in the analysis of central pulse waveform variables assessed by carotid tonometry. METHODS: Eighty-four patients (age: 67.1 ±â€Š12.4 years) undergoing screening for carotid atherosclerosis were enrolled, divided into three groups according to carotid ultrasound findings (NASCET criteria): 28 patients without significant stenosis, 30 patients with bilateral plaques, and 26 patients with right or left monolateral stenosis. PWV and other variables derived from the central pulse waveform analysis (central blood pressure, augmentation index and forward and backward waves) were measured at both right and left carotid arteries by a validated PulsePen tonometer. A repeatability study was performed in 28 young healthy patients (age: 25.4 ±â€Š2.9 years). RESULTS: A high degree of correlation was found between bilateral measurements in all groups, and particularly in groups with monolateral carotid stenosis, with no significant difference attributable to lateralized stenosis. Right-left differences in asymmetric groups were 0.35 ±â€Š5.12 mmHg (R = 0.960) for central blood pressure, -2.12 ±â€Š7.39% (R = 0.743) for augmentation index, 0.64 ±â€Š1.56 m/s (R = 0.947) for PWV, 0.08 ±â€Š8.48 mmHg for forward wave (R = 0.742) and 0.35 ±â€Š2.35 mmHg for backward wave (R = 0.907). CONCLUSION: Measurement of PWV and of variables derived from the central pulse waveform analysis by carotid tonometry is not biased by the presence of local atherosclerotic plaques.

A case report of malignant hypertension in a young woman.

BACKGROUND: Malignant hypertension is a condition characterized by severe hypertension and multi-organ ischemic complications. Albeit mortality and renal survival have improved with antihypertensive therapy, progression to end-stage renal disease remains a significant cause of morbidity and mortality. The underlying cause of malignant hypertension, which can be primary or secondary hypertension, is often difficult to identify and this can substantially affect the treatment outcomes, as we report here. CASE PRESENTATION: A 33-year-old woman presented with severe hypertension and acute renal failure. Initial evaluation demonstrated hyperreninemia with hyperaldosteronism and a possible renal artery stenosis at the contrast-enhanced CT scan. Although this data suggested the presence of a secondary form of hypertension, further exams excluded our first diagnosis of renal artery stenosis. Consequently, the patient did not undergo renal angiography (and the contrast media infusion associated with it), but she continued to be medically treated to achieve a tight blood pressure control. Our conservative approach was successful to induce renal function recovery over 2 years of follow-up. CONCLUSION: This case highlights the difficulty in differentiating between primary and secondary forms of malignant hypertension, particularly when the patient presents with acute renal failure. Clinicians should consider renal artery ultrasound as a first level diagnostic technique, given that the presentation of primary malignant hypertension can often mimic a renal artery stenosis. Secondly, adequate control of blood pressure is essential for kidney function recovery, although this may require a long time.

Baroreflex sensitivity and central hemodynamics after omega-3 polyunsaturated fatty acids supplementation in an animal model of menopause.

OBJECTIVE: Baroreflex sensitivity (BRS) and central arterial function are significantly worsened after menopausal transition. This study tested the hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA) might contribute to prevent these adverse changes in the vascular function of ovariectomized rats, an animal model of experimental menopause. METHODS: We randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL), sham surgery, normal diet; ovariectomized with normal diet (OVX) and ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d) (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic response to phenylephrine-induced blood pressure increase, while large artery function was estimated by the graphical analysis of the aortic pressure wave (diastolic to systolic pressure-time integral ratio, DTI/STI). RESULTS: Ovariectomy caused a significant decrease in BRS (CTRL: 6.23±0.68ms/mmHg; OVX: 2.85±0.75; p<0.001). n-3 PUFA supplementation prevented part of the decline of BRS caused by surgical menopause (OVX+O3: 4.75±0.53; p<0.01 vs OVX). In animals treated with n-3 PUFA, the central arterial pressure profile did not show the changes in DTI/STI ratio seen in OVX (OVX: 3.31±1.72; OVX+O3: 3.83±1.52; p<0.01). CONCLUSIONS: In an experimental model of menopause, treatment with n-3 PUFA normalized central hemodynamics and prevented the decrease in BRS, associated with the reduction of compliance of the arterial wall. These findings suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of postmenopausal vascular disease.

Ambulatory Blood Pressure Monitoring-Derived Short-Term Blood Pressure Variability in Primary Aldosteronism.

The aim of this study was to investigate the short-term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone-producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24-hour, daytime, and nighttime BP; 24-hour weighted SD of BP; and 24-hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM-derived short-term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified.

Supplementation of omega-3 polyunsaturated fatty acids prevents increase in arterial stiffness after experimental menopause.

BACKGROUND: Menopause is associated with increased arterial stiffness, an independent marker of cardiovascular risk. Omega-3 polyunsaturated fatty acids (N3-PUFAs) are thought to have multiple cardiovascular benefits, including prevention of arterial stiffness. We investigated whether treatment with N3-PUFA prevents increase in arterial stiffness in ovariectomized rats, an animal model of experimental menopause. METHODS: A total of 43 Wistar rats, 2 months old, were divided into 3 groups, control, sham surgery, normal diet (CTRL, n = 15); ovariectomy, normal diet (OVX, n = 14); and ovariectomy with N3-PUFA supplementation (0.8 g/kg/d in daily gavages administration; OVX + O3, n = 14). Two months after surgery, carotid-femoral pulse wave velocity (PWV) and arterial blood pressure (BP) were measured by carotid and femoral cannulation. Aortic morphometric measurements were performed after dissection. RESULTS: Ovariectomy caused a significant increase in BP (P < .05), PWV (P < .0001), and elastic modulus (P = .001) compared to CTRL. After ovariectomy, N3-PUFA supplementation completely prevented increase in arterial stiffness (P < .0001 vs OVX) and BP (P < .05 vs OVX) and resulted in a significant increase in body weight and aortic thickness. CONCLUSIONS: In an experimental model of menopause, N3-PUFA supplementation prevents arterial stiffening and other vascular changes induced by ovariectomy. These results represent a therapeutic benefit of N3-PUFAs in prevention of postmenopausal cardiovascular disease.

Ambulatory arterial stiffness indexes in acromegaly.

OBJECTIVE: Acromegaly is associated with increased cardiovascular morbidity and mortality and with specific heart and vascular abnormalities. The aim of our study was to investigate arterial stiffness using the ambulatory arterial stiffness index (AASI) and symmetric AASI (Sym-AASI), two indexes derived from 24-h ambulatory blood pressure monitoring (ABPM), in a group of normotensive and hypertensive patients with active acromegaly, compared with normotensive controls (NOR-CTR) or hypertensive controls (HYP-CTR). SUBJECTS AND METHODS: Ninety-six consecutive patients with active acromegaly (46 males, mean age 49±14 years) underwent 24-h ABPM and evaluation of cardiovascular risk factors. Based on ABPM measurement, acromegalic patients were divided into 64 normotensive (normotensive acromegalic patients (NOR-ACRO)) and 32 hypertensive (hypertensive acromegalic patients (HYP-ACRO)) patients, and were compared with 35 normotensive (NOR-CTR) and 34 hypertensive (HYP-CTR) age-, sex,- and ABPM-matched control subjects. RESULTS: The AASI and Sym-AASI indexes were significantly higher in acromegalic patients than in controls, either in the normotensive (NOR-ACRO vs NOR-CTR, P<0.0001 for AASI and P=0.005 for Sym-AASI) or in the hypertensive (HYP-ACRO vs HYP-CTR, P=0.01 for AASI and P=0.01 for Sym-AASI) group. Multiple logistic regression analysis showed a significant association of the highest AASI tertile with serum IGF1 (P=0.034) in the whole acromegalic group. CONCLUSION: AASIs are increased in acromegaly, independent of blood pressure (BP) elevation, and may have an important role in predicting cardiovascular risk in this disease.

Imaging for renovascular disease.

Renal artery stenosis is frequently considered in the diagnosis of severe hypertension and renal insufficiency, but the benefits of screening and the choice of imaging modalities is controversial. Sonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA), and conventional angiography are all used and each has advantages and disadvantages. However, performance and interpretation of each requires significant experience and expertise. Since there are no clear data or consensus on the choice of imaging modalities, this should be based on the level of expertise that is available.

Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: potential role of the renin-angiotensin system.

OBJECTIVES: The mechanisms underlying the increased cardiovascular risk after menopause are poorly understood. Estrogens modulate the cardiac renin-angiotensin system (RAS) and influence cardiac adaptation to afterload. To investigate whether the loss of the natural inhibition of the RAS by estrogen may be linked to an increase of cardiac apoptosis, we studied 17ß-estradiol (E2) and/or angiotensin-converting enzyme (ACE) inhibitor treatment effects on cardiomyocyte survival in ovariectomized spontaneously hypertensive rats (SHRs). METHODS: Five groups of female SHRs were evaluated for 8 weeks. One group served as nonovariectomized control; the other four groups underwent bilateral ovariectomy and were randomized to receive 60-day-release pellets containing placebo or 0.5 mg of E2, the ACE inhibitor ramipril at the dosage of 2.5 mg/kg per day, or the combination of the two treatments. RESULTS: Ovariectomy increased cardiomyocyte apoptosis and induced proapoptotic changes of Bcl-2 and Bax genes and proteins. These modifications were associated with an upregulation of ACE and angiotensin II type 1 (AT1) receptor genes. Ramipril was as effective as E2 in preventing cardiac apoptosis and in restoring cardiac brain natriuretic peptide in association with reduced cardiac ACE and AT1 receptor gene expression. In contrast to the ramipril treatment, the favorable effect of E2 on cardiac apoptosis occurred independently from changes in SBP. No synergistic effect was observed when the two treatments were combined. CONCLUSION: These data show that ovariectomy stimulates myocardium apoptosis by a mechanism involving Bax and Bcl-2 genes. The antiapoptotic effect of E2 and ACE inhibitor treatment was linked to a downregulation of cardiac RAS.

Dose and time-dependent apoptotic effects by angiotensin II infusion on left ventricular cardiomyocytes.

OBJECTIVE: To gain insight into the regulation of cardiac apoptosis we studied the dose-response and time-course effects of angiotensin II (Ang II) infusion on ventricular cardiomyocyte apoptosis and on the expression of Bax and Bcl-2 genes and proteins. STUDY DESIGN AND METHODS: In the dose-response study, Ang II was infused subcutaneously at doses of 100, 200, 400, 800 and 1200 ng/kg per min for 14 days. In the time-course study, rats infused with Ang II at doses of 200 and 400 ng/kg per min were followed for 7 and 14 days. The cardiomyocyte apoptotic density was assessed by DNA end labelling (terminal deoxynucleotide nick-end labelling; TUNEL). Gene and protein expression of Bcl-2 and Bax were evaluated by reverse transcriptase-polymerase chain reaction and by Western blots. RESULTS: Systolic blood pressure and left ventricular mass were increased in a dose-dependent manner in Ang II-infused rats. A statistically significant increase in the rate of cardiac apoptosis and pro-apoptotic changes of Bcl-2 and Bax gene and protein expression was observed when high doses of Ang II (800-1200 ng/kg per min) were infused. A positive correlation of apoptotic density with Bax and a negative correlation with Bcl-2 and Bcl-2/Bax ratio were found. Cardiac apoptosis was greatly influenced by the timing of Ang II infusion. Losartan-treated Ang II-infused rats exhibited normalized systolic blood pressure, left ventricular weight, apoptosis, and Bax and Bcl-2 levels. CONCLUSIONS: Our results are consistent with the pathophysiological role of Ang II in induction of cardiac apoptosis, and explain the cardioprotective effect of Ang II receptor antagonists.

Glomerular permeability defect in hypertension is dependent on renin angiotensin system activation.

BACKGROUND: The aim of the present study was to compare glomerular permeability alterations associated with experimental hypertension models known to have different effects on the circulating renin-angiotensin system (RAS). METHODS: Five groups, 10 animals each, were studied. One group served as a nonhypertensive control. The other four groups of hypertensive animals were composed of spontaneously hypertensive rats, deoxycorticosterone acetate hypertensive rats, Goldblatt two-kidney, one-clip rats, and a group of Wistar rats infused with angiotensin II (200 ng/kg/min). Tail-cuff sphygmomanometric systolic blood pressure (BP), albumin permeability determined in isolated glomeruli exposed to oncotic gradients (P(alb)), glomerular filtration rate (GFR, iopamidol method), plasma renin activity (PRA), and albuminuria were evaluated. RESULTS: Alterations in P(alb) and albumin excretion rate were more evident in the experimental models with an activation of the RAS despite similar levels of systolic BP and GFR. A positive correlation was found between P(alb) and albuminuria (r = 0.51; P < .001) and between systolic BP and albuminuria (r = 0.37; P < .01). No relation was found between systolic BP and P(alb). CONCLUSIONS: The present study indicates that the activation of the RAS plays a significant role in the development of glomerular albumin permeability defects in hypertensive models and may contribute to the mechanisms that lead to target organ damage in hypertension.

Large-artery hemodynamics after acute alcohol administration in young, healthy volunteers.

The objective of the present study was to investigate the acute effects of alcohol on blood flow volume and velocity, on wall motion of superficial large arteries, and on systemic hemodynamics in humans. In 10 healthy volunteers small doses of alcohol were administered either orally (0.3 g/kg in 250 mL water) or intravenously (7.5 mg/kg/minute in 250 mL saline in 40 minutes). The effects of alcohol were compared with those of saline 250 mL infused for 40 minutes (6.25 mL/min). Blood velocity and systodiastolic changes of wall diameter were measured in the common carotid, femoral, and brachial arteries simultaneously with cardiac output and finger blood pressure. Skin temperature was measured at the cheek, hand, and toe. Ethanol administration caused a transitory blood pressure increase accompanied by a rise in peripheral resistances at 20 minutes. Arterial blood flow was not changed by either mode of alcohol administration at any of the measurement sites. However, this result was achieved through different compensatory mechanisms in each artery. In fact, mean carotid diameter increased after both oral and intravenous ethanol administration but remained unchanged at the brachial and femoral level. Mean blood velocity was reduced after alcohol administration at the carotid but was unchanged at the brachial and femoral level after oral or intravenous alcohol administration. Skin temperature increased 20 minutes after alcohol administration at all sites. This study shows that although acute alcohol administration does not change blood flow in superficial large arteries, it causes different autoregulatory local responses of vessel walls.