High Plasma Renin Activity Research Articles

Diagnostic Role of Renal Doppler Ultrasound and Plasma Renin Activity as Screening Tools for Renovascular Hypertension in Children.

The diagnostic role of an ultrasound (US) and plasma renin activity (PRA) combination is unknown, despite the usefulness of Doppler US as a screening tool for renovascular hypertension (RVHT). The purpose of this study was to evaluate the diagnostic usefulness of US for RVHT in children stratified according to PRA. We identified 336 children who underwent renal Doppler US examinations for hypertension and divided them into a high-renin group (n = 177) and a normal-renin group (n = 159) based on PRA and stratified them by age. The Doppler US findings were retrospectively reviewed, and computed tomographic angiography (CTA) for the same children was used as the reference standard. In the high-renin group, 36 patients had positive Doppler US findings that were confirmed by CTA in 32 cases. The sensitivity and specificity values for Doppler US in the high-renin group were 84.2% and 93.6%, respectively. In the normal-renin group, 10 patients had positive Doppler US findings; these positive findings were confirmed by CTA in 9 cases. The sensitivity and specificity values for US in the normal-renin group were 100.0% and 100.0%. There were anatomic variations (n = 3) and segmental artery stenosis (n = 2) among the cases with false-negative US findings, which were confirmed by CTA. If patients have high PRA, a Doppler US examination should be performed with caution to avoid false-negative detection. If patients have normal PRA, renal Doppler US might be adequate for diagnosis of RVHT to avoid unnecessary CTA.

Low plasma renin activity is an independent predictor of near-term incidence of hypertension in Asian populations

ABSTRACTBackground: Plasma renin activity is involved in the regulation of body salt content and blood pressure. However, there is a paucity of data regarding the association between low or high plasma renin activity and the development of hypertension.Method: We investigated the relation of baseline plasma renin activity to increases in blood pressure and the incidence of hypertension after four years in 2,146 non-hypertensive individuals from a community-based Korean population (mean age, 50 years), 58% of whom were women. We defined an “increase in blood pressure” as an increment of systolic blood-pressure ≥ 10 mmHg or initiation of antihypertensive drugs and defined “hypertension” as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications.Results: After 4 years, the increase in blood pressure had increased in 27.9% of the participants, and hypertension had developed in 17.9%. After adjustment, the lowest sex-specific tertile of plasma renin activity was an independent risk factor of an elevation in blood pressure (Adjusted Odds Ratio 1.37, 95% confidence interval 1.07–1.74, p = 0.011) and hypertension (Adjusted Odds Ratio 1.84, 95% confidence interval 1.36–2.50, p < 0.001) compared to the highest sex-specific tertile. The associations between the plasma renin activity and blood-pressure outcomes were evident in adults with especially high urine sodium excretion.Conclusion: Low plasma renin activity was associated with the development of hypertension in the middle-aged Asian population, especially in peoples with high sodium intake.

Bilateral renal cryodenervation decreases arterial pressure and improves insulin sensitivity in fructose-fed Sprague-Dawley rats.

Consumption of food high in fructose is prevalent in modern diets. One week of moderately high fructose intake combined with high salt diet has been shown to increase blood pressure and failed to suppress plasma renin activity (PRA). We tested the hypothesis that the hypertension and high PRA are consequences of elevated renal sympathetic nerve activity (RSNA). In protocol 1, we assessed RSNA by telemetry in conscious Sprague-Dawley rats given 20% fructose or 20% glucose in drinking water on a 0.4% NaCl diet (NS) for 1 wk and then transitioned to a 4% NaCl diet (HS). After an additional week, mean arterial pressure (MAP) and RSNA increased significantly in fructose-fed but not glucose-fed HS rats. In protocol 2, fructose (Fruc)- or glucose (Glu)-fed rats on NS or HS diet for 3 wk underwent sham denervation (shamDNX) or bilateral renal denervation using cryoablation (cryoDNX). MAP was higher in Fruc-HS rats compared with Glu-NS, Glu-HS, or Fruc-NS rats and decreased after cryoDNX ( P < 0.01). MAP did not change in Fruc-HS shamDNX rats. Renal norepinephrine content decreased by 85% in cryoDNX ( P < 0.01 vs. shamDNX). PRA significantly decreased after cryoDNX in both Fruc-NS and Fruc-HS rats. Nonfasting blood glucose levels were similar among the four groups. Glucose-to-insulin ratio significantly increased in Fruc-HS cryoDNX rats, consistent with greater insulin sensitivity. Taken together, these studies show that renal sympathoexcitation is, at least in part, responsible for salt-dependent increases in MAP, increased PRA, and decreased insulin sensitivity in rats fed a moderately high fructose diet for as little as 3 wk.

A case of an infant suspected as IMAGE syndrome who were finally diagnosed with MIRAGE syndrome by targeted Mendelian exome sequencing

BackgroundAdrenal hypoplasia is a rare congenital disorder, which can be classified into a non-syndromic form, without extra-adrenal features, and a syndromic form, with such features. Despite biochemical and molecular genetic evaluation, etiologic diagnosis cannot be performed in many patients with adrenal hypoplasia.Case presentationThe patient in this case was a boy born at 31 weeks of gestation with a weight of 882 g (< 3rd percentile) to non-consanguineous parents. Genital examination showed micropenis and bilateral cryptorchidism. On the third day of life, he manifested hypotension with high urine output, hyponatremia, hyperkalemia, hypernatriuria, high plasma adrenocorticotropic hormone level, and high plasma renin activity, suggesting acute adrenal insufficiency. The serum 17α-hydroxyprogesterone level was normal. Adrenal insufficiency improved following administration of hydrocortisone and 9α-fludrocortisone, but the patient died of recurrent infection at 4 months of age. He was suspected as IMAGE (Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies) syndrome. However, no mutation in CDKN1C was identified. Targeted exome sequencing using the TruSight One Sequencing Panel (Illumina) identified a heterozygous mutation of c.2944C > T (p.R982C) in exon 3 in SAMD9.ConclusionThis report describes the first Korean case of MIRAGE syndrome. The patient presented with severe primary adrenal insufficiency, intrauterine growth retardation, and recurrent infection. SAMD9 mutation should be considered in patients who present with adrenal hypoplasia and extra-adrenal phenotypes.

PP.07.16] RELATIONSHIP BETWEEN PLASMA RENIN ACTIVITY, PLASMA ALDOSTERONE AND SELECTED ASYMPTOMATIC ORGAN DAMAGE INDICES IN ESSENTIAL ARTERIAL HYPERTENSION

Objective: To assess the relationship between plasma renin activity (PRA), serum aldosterone concentration (ALDO) and selected asymptomatic organ damage (AOD) indices in mild primary arterial hypertension (AH).Design and method: In 122 patients (61 men and 61 women) with untreated essential AH stage 1 (140/90 > BP < 160/100 mm Hg) and age 30–75 years we measured PRA, ALDO, and selected AOD indices (left ventricular mass index, carotid artery intima media thickness, carotid-femoral pulse wave velocity (cfPWV), central aortic pulse pressure (cPP), estimated glomerular filtration rate (eGFR)). Although the study group included only patients with mild essential AH without typical indications to perform screening for primary aldosteronism we decided to exclude patients with an aldosterone-to-renin ratio (ARR) >100 ng/dl/ng/ml/h and aldosterone concentration >15 ng/dl. Results: Based on PRA results, patients were divided into two subgroups, “low-renin” and “high-renin”, according to the Laragh and Alderman criteria (low-renin: PRA < 0.65 ng/ml/h, high-renin: PRA > 0.65 ng/ml/h). Patients with high PRA (>0.65 ng/ml/h) were characterized by lower plasma sodium concentration, several times lower aldosterone-to-renin ratio (ARR), higher ALDO, but similar level of AOD indices compared to patients with low PRA. Among AOD indices, cfPWV (p = 0.04) and cPP (p = 0.019) increased with ARR, while eGFR decreased with ALDO (p = 0.008). After adjusting for age, sex, and BMI, only eGFR was significantly correlated with ALDO (Table 1). In subjects with simultaneously high PRA and ARR values, we found significantly higher cfPWV (p = 0.02) and cPP (p = 0.04) and lower eGFR (p = 0.02) than in those with high PRA but low ARR values. Conclusions: In mild hypertension, assessment of RAAS influence on AOD should include the reciprocal relationship between renin and aldosterone. PRA itself has no predictive value for AOD. More advanced arterial stiffness and renal impairment are associated with increased PRA and ARR. RAAS activity might be useful in AOD prediction and hypertension severity assessment.

Muscle sympathetic nerve activity and volume-regulating factors in healthy pregnant and nonpregnant women.

Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In nonpregnant humans, volume-regulatory factors including plasma osmolality, vasopressin, and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume-regulating factors, including plasma osmolality, plasma renin activity, and arginine vasopressin (AVP). We studied 46 healthy, normotensive young women (23 pregnant and 23 nonpregnant). We measured SNA, arterial pressure, plasma osmolality, plasma renin activity, AVP, and other volume-regulatory factors in resting, semirecumbent posture. Pregnant women had significantly higher resting SNA (38 ± 12 vs. 23 ± 6 bursts/min in nonpregnant women), lower osmolality, and higher plasma renin activity and aldosterone (all P < 0.05). Group mean values for AVP were not different between groups [4.64 ± 2.57 (nonpregnant) vs. 5.17 ± 2.03 (pregnant), P > 0.05]. However, regression analysis detected a significant relationship between individual values for SNA and AVP in pregnant (r = 0.71, P < 0.05) but not nonpregnant women (r = 0.04). No relationships were found for other variables. These data suggest that the link between AVP release and resting SNA becomes stronger in pregnancy, which may contribute importantly to blood pressure regulation in healthy women during pregnancy.NEW & NOTEWORTHY Sympathetic nerve activity and blood volume are both elevated during pregnancy, but blood pressure is usually normal. Here, we identified a relationship between vasopressin and sympathetic nerve activity in pregnant but not nonpregnant women. This may provide mechanistic insights into blood pressure regulation in normal pregnancy and in pregnancy-related hypertension.

Successful long-term effects of direct renin inhibitor aliskiren in a patient with atherosclerotic renovascular hypertension.

A 64-year-old man visited our hospital with complaints of misty vision and ophthalmalgia. On admission, his blood pressure (BP) was high at 220/135mmHg with no past history of hypertension, and he had choked discs. He was tentatively diagnosed as having idiopathic intracranial hypertension, and was later found to have atherosclerotic unilateral renovascular hypertension (RVH) based upon the extremely high plasma renin activity together with the radiological image tests. On day 3, combined antihypertensive therapies consisting of oral angiotensin II receptor blocker (ARB) and Ca channel blocker (CCB) along with intravenous CCB induced an abrupt BP lowering which led to deterioration of his renal function, progressing into acute kidney injury (AKI). Cessation of the ARB and reduction of the CCB dose ameliorated the AKI-related decline in renal function. On day 17, as he was reluctant to receive surgical intervention, he was treated with a direct renin inhibitor, aliskiren, combined with a half-dose CCB as a maintenance antihypertensive therapy. The therapy has proven not only successful to chronically maintain his renal function but was also capable of controlling his BP in the neighborhood of 130/85mmHg over a period of 2 years. The present case suggests that the direct renin inhibition with aliskiren can be a safe and useful antihypertensive option to control hypertension and to preserve renal function in patients with atherosclerotic unilateral RVH.

Comparison of the concentration of leptin between obese women and obese men with essential hypertension

Background The main determinants of the level of leptin in human plasma are the fat mass and sex. In recent literature many papers have been published indicating the participation of leptin in the pathogenesis of essential hypertension. The aim of this study was to compare serum levels of leptin and evaluate its importance in the pathophysiology of hypertension in obese men and women. Material and methods The study was conducted in a group of a total of 52 obese individuals (26 women and 26 men) with newly diagnosed essential hypertension. The study protocol included blood sample collection for the measurements of biochemical parameters and hormone levels. Biochemical assays were performed using routine methods. Serum insulin was determined by immunoradiometric assay (IRMA). The index of insulin resistance (IR) was calculated using HOMA. Leptin, plasma renin activity (PRA) and plasma aldosterone concentration were determined by radioimmunoassay (RIA). Results No significant differences were found between women and men in terms of age, BMI, blood pressure, total cholesterol, LDL and fasting glucose. Men had slightly but significantly higher waist circumference. The group of women had significantly higher levels of leptin, insulin and insulin resistance, and a higher PRA and aldosterone levels than males. In the group studied, leptin significantly positively correlated with blood pressure, as well as with the concentration of aldosterone and renin both in women and in men. There was no similar relationship between leptin and insulin and the insulin resistance index. Conclusions Women with obesity and hypertension have higher levels of leptin than obese men with hypertension. Reported correlations between plasma leptin concentration and blood pressure suggest that it is directly or indirectly involved in the pathophysiology of hypertension in obese individuals regardless of gender.

082 - Plasma Renin Activity in Distinct Patient Populations with Heart Failure and Reduced Ejection Fraction

Background: Renin-angiotensin-aldosterone system (RAAS) activation in heart failure with reduced ejection fraction (HFREF) is detrimental through cardiac remodeling and water/salt retention. Aims: This study aims to describe RAAS activity in distinct HFREF populations—acute decompensation, chronic HFREF and HFREF with normalized ejection fraction after cardiac resynchronization therapy (CRT)—and to assess its prognostic impact. Methods and Results: In 72 acute decompensated HFREF patients (ADHF), 78 chronic HFREF patients without clinical signs of congestion and 53 patients with HF with normalized ejection fraction (HFNEF), venous blood samples and hemodynamic parameters were obtained. Subjects were prospectively followed up to 30 months. Plasma renin activity (PRA) is significantly lower in ADHF (1.5 ng/ml/h [0.8;5.7]) compared to stable HFREF (7.6 ng/ml/h [2.2;18.1] and HFNEF patients (3.9 ng/ml/h [1.0;13.0]) (all P < .05) (Fig. 1). PRA was significantly associated with arterial blood pressure, renin-angiotensin system blocker dose, beta-blocker dose, and mineralocorticoid receptor antagonist use (all P < .05) but not with age, left ventricular ejection fraction, heart rate, loop diuretic dose, creatinine or NT-pro BNP (all P > .05). High PRA levels are associated with increased cardiovascular mortality or HF admission in acute ADHF, but not in stable HFREF or HFNEF (Fig. 2). Conclusion: PRA is significantly elevated in ambulatory chronic HFREF patients, even when ejection fraction has normalized after CRT which is associated with blood pressure and medication use. Yet, in contrast to ADHF where PRA levels predict cardiovascular mortality and rehospitalizations, PRA levels are not associated with outcome in chronic HFREF and HFNEF.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pseudohypoaldosteronism in a Neonate Presenting as Life-Threatening Hyperkalemia.

Context. Pseudohypoaldosteronism type 1 (PHA1) is a life-threatening disease that causes severe hyperkalemia and cardiac arrest if not treated appropriately or if diagnosis is missed. Objective. To report a case of a newborn with vomiting and lethargy, ultimately diagnosed with pseudohypoaldosteronism. Patient. This case presented to the ED at an age of 14 days in hypovolemic shock. There was a family history of sudden infant death, her sister who was diagnosed with CAH and passed away at 3 months of age despite regular hormone replacement. Our patient had cardiac arrest in ED, due to hyperkalemia; while receiving fluid boluses, cardiopulmonary resuscitation was initiated. After stabilization, diagnostic workup demonstrated persistently low sodium, acidosis, and high potassium, which required peritoneal dialysis. Based on these findings, the patient was diagnosed with CAH. It turned out later that the patient had PHA1. Two years later, the patient had a new sibling with the same disease diagnosed at birth and started immediately on treatment without any complication. Conclusions and Outcome. This case highlights the significant diagnostic and therapeutic challenges in treating children with PHA1. Adrenal crisis is not always CAH; delayed diagnosis can lead to complication and even death. The presence of high plasma renin activity, aldosterone, and cortisol, along with the presence of hyponatremia and hyperkalemia, established the diagnosis of PHA type 1 and ruled out CAH.

Abstract 14714: Association of Plasma Renin and Aldosterone Levels With Future Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: The renin-angiotensin-aldosterone-system (RAAS) has been implicated in left ventricular (LV) hypertrophy and dysfunction. We explore the association of circulating levels of plasma renin activity (PRA) and aldosterone to subclinical measures of LV structure and function from MRI. Methods: The MESA study enrolled 6814 participants free of cardiovascular disease at baseline (2000-2002). We included MESA participants who had blood assayed for measurement of PRA and aldosterone levels at the second/third follow-up exams (2003-2005) and underwent MRI at the fifth follow-up exam (2010 -2012). We excluded participants on hypertension medication (N=509). Harmonic phase analysis was used to compute circumferential strain and torsion from tagged MRI; LV function and structure measures were obtained from cine images. Linear regression evaluated the relationship between PRA, aldosterone and aldosterone to renin ratio (ARR) with LV structure and function. The models included adjustments for cardiovascular risk factors and demographics at the time of assays (model 1) and at the time of imaging (model 2) separately. Results: At the time of assays, the participants (N=384) were 59±8 years, 53% male, 43% Caucasian, 13% African-American, 17% Chinese, 28% Hispanic, 4% diabetic, with median levels of PRA 0.56 ng/ml (IQR:0.30-0.97), aldosterone 126 pg/ml (IQR:90-176) and ARR 120 ng/ml to pg/ml (IQR:53-234). Higher PRA was associated with lower LV end-diastolic volume index. Higher PRA was associated with higher mass-volume ratio and torsion. Higher ARR was associated with higher LV volume and lower torsion. Conclusions: In individuals not on hypertension medications, higher PRA was associated with concentric remodeling and higher torsion 7 years later but not to LV function. Also, higher ARR was associated with eccentric LV chamber remodeling and lower torsion. In conclusion, RAAS activity may be implicated in future concentric/eccentric LV remodeling.

Prognostic Impact of B-type Natriuretic Peptide Levels and Plasma Renin Activity in Female Patients with Acute Decompensated Heart Failure

In acute decompensated heart failure (ADHF), the number of female patients has been increasing but their prognostic factors has remained uncertain. We have studied consecutive 252 female patients with ADHF admitted to our department from 2007 through 2012. Of 252 patients, 170 patients whose BNP levels and plasma renin activity (PRA) were examined. We divided into two groups on the basis of the median BNP levels and PRA. Kaplan-Meier analysis revealed that high PRA groups had worse prognosis than low PRA groups (p<0.01), but BNP levels could not predict cardiovascular death and HF admission (Figure 1). Multivariate analysis revealed that PRA predicted cardiac event (HR: 1.029 [1.005-1.050], p<0.05) but BNP levels were not. PRA was stronger predictors of cardiac events than BNP levels in ADHF patients.

Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease

There are currently no published data on post-paracentesis circulatory dysfunction (PPCD) or its prevention in children. Our study was aimed to analyze the safety and complications of large volume paracentesis (LVP) in children with severe ascites due to chronic liver disease with or without albumin therapy. A prospective longitudinal observational study enrolled children with severe ascites who underwent single time LVP at admission. They were divided into albumin infused (AI) and albumin non-infused (ANI) groups. Hemodynamic monitoring and laboratory parameters including plasma renin activity (PRA) were compared between baseline, 48 h and day 6 of LVP. Their outcome at 3 months and maximal follow-up were noted. 32 children (AI, n=17; ANI, n=15) had comparable baseline characteristics and 90.6% had high PRA at onset. The incidence of PPCD was 37.5% (ANI: 67%; AI: 12%, p=0.003), occurred if ascitic fluid extraction was >197.5 ml/kg (sensitivity: 90%; specificity: 50%, p=0.01) and if flow rate was higher in ANI group (1224 ± 476 vs. 678 ± 214 ml/h, p=0.009). ANI patients were susceptible to asymptomatic, persistent hyponatremia (baseline vs. day 6, 131 ± 4 vs. 128 ± 6 mEq/L; p=0.04) and had higher rates of recurrent ascites (42%) and hospital readmission (67%) within 3 months. No survival benefit among the AI or non-PPCD groups was demonstrated. LVP is safe in all age groups, best performed under albumin cover to overcome the problems of PPCD and hyponatremia. It is prudent to restrict volume extraction to less than 200 ml/kg actual dry weight for all and flow rate of 680 ml/h in ANI.

The Ratio of Plasma Aldosterone Concentration to Potassium in Adrenocorticotropin Stimulation Test is a Possible New Index for Diagnosis of Aldosterone-producing Adenoma in Patients with Primary Aldosteronism

Primary aldosteronism (PA)is the most common form of secondary hypertension,and is characterized by high plasma aldosterone concentration (PAC)and low plasma renin activity(PRA),refractory hypertension, and occasional hypokalemia. Reliable parameters are required to identify aldosterone-producing adenoma (APA)in patients with PA,because APA is treatable with surgical resection if localization of aldosterone hypersecretion can be determined by adrenal venous sampling (AVS).The purpose of this study is to summarize the results of AVS in our institute and to evaluate the diagnostic accuracy of various parameters with adrenocorticotropic hormone(ACTH)stimulation test in identifying probable APA among patients with PA. Eighty-one patients with PA were admitted to Shinshu University Hospital from April 2009 to March 2013,and 59 patients who underwent AVS were included in the study.PAC and aldosterone to potassium ratio (APR) in ACTH stimulation tests were examined in 28 patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic accuracy.The response of PAC to ACTH in the probable APA group was stronger than that in the others.In ROC curve analysis,the area under the curve(AUC)of APR (PAC / potassium)for diagnosis of probable APA was 0.9840 with an optimal cutoffvalue>102.6 corresponding to sensitivity and specificity of 94.1% and 90.9 % for diagnosis of APA,respectively.This study indicated that APR after the ACTH stimulation test may be a useful and accurate parameter in cases of PA.In cases with APR 100 after ACTH stimulation,AVS is strongly recommended for localization of aldosterone hypersecretion.Shinshu Med J 63 : 145―156, 2015 (Received for publication December 8,2014;accepted in revised form January 28,2015)

PP.11.05

Objective: Plasma renin activity (PRA) is accepted as a marker for increased risk of cardiovascular diseases. We examined whether PRA is a risk factor left ventricular structure abnormal in hypertension patients of Han Chinese.Design and method: This cross-sectional study included a total of 879 consecutive Han patients diagnosed essential hypertension who were hospitalization at Department of Hypertension in People's Hospital of Xinjiang Uygur Autonomous Region in China between 2009 and 2013, subjects aged from 30 years to 60 years. All participants who had not taken antihypertensive drugs at least four weeks, or stopped the drug to effect hormone, such as contraception pills, diuretic dihydropyridines calcium antagonist, beta blockers, angiotensin converting enzyme inhibitors and angiotensin II receptor inhibitor. 24-h ambulatory blood pressure monitoring, echocardiography, plasma renin activity and plasma aldosterone were also performed. LV mass index (LVMI) was calculated according to the method of Devereux and Reichek. LV hypertrophy (LVH) was defined as LVMI>=125 g/m2 in men and >=110 g/m2 in women. According to LVMI and RWT, concentric remodeling (CCR), a normal LVMI and RWT>=0.45; concentric hypertrophy (CCH), RWT<0.45 and LVH; eccentric hypertrophy (ECH) RWT>=0.45 and LVH. According to the plasma renin activity lever, participants were classified three renin categories, as follows: low renin, <0.56ng/ml/h (30% of the sample); medium renin, 0.56 to 4.24ng/ml/h (60% of the sample); or high renin,>4.24ng/ml/h(10% of the sample) Results: As compared with low-renin and medium-renin groups, high-renin group had high mean 24-h mean arterial pressure. High-renin group show a high prevalence of LVMI and concentric hypertrophy, eccentric hypertrophy than low and medium renin groups adjusting for sex, age, BMI, and mean 24 hours MAP. Regression models showed that high-renin group showed significantly increased 3.033 fold risk of left ventricular hypertrophy (p < 0.001), compared to low-renin group, as potential confounders for age, gender, BMI, serum creatinine, high-sensitivity C-reactive protein, triglyceride,duration. Conclusions: These results raise the hypothesis that high plasma renin activity may have a deleterious effort on the development of LV structure in essential hypertension.

Glycosylated haemoglobin is associated with neurohormonal activation and poor outcome in chronic heart failure patients with mild left ventricular systolic dysfunction.

We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin [HbA(1c)] on neurohormonal activation and outcome in chronic heart failure (CHF). Nine hundred and twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles. Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.

PP.23.22

Objective: Primary aldosteronism (PA) has been associated with excess left ventricular (LV) hypertrophy, but whether this is also a feature of secondary aldosteronism (SA) without hypertension is uncertain. We therefore investigated the cardiac changes in patients with PA and SA, who had preserved LV ejection fraction, but had contrasting levels of blood pressure (BP) and plasma renin activity (PRA). Design and method: PA patients (n 278) were compared to SA (n 117) patients with liver cirrhosis for PRA, aldosterone, and multiple Doppler echocardiography-derived variables. Healthy subjects (HS, n 60) were used as controls. LV systo/diastolic function was assessed also by use of tissue Doppler imaging and strain-rate analysis. Results: HS and SA patients showed normal BP values, but SA showed increased heart rate, reduced peripheral vascular resistance and increased cardiac index, output and work (p < 0.0001). PA showed higher BP values than SA and HS (p < 0.0001). SA and PA showed high and low PRA values (15 ng/ml/hr vs 0.56 ng/ml/hr, p < 0.0001) respectively, in spite of similarly elevated aldosterone levels (66 ng/dl vs 42 ng/dl, respectively). Of interest, in both PA and SA the LV mass index (51.4 and 54.3 g/m2,7) was higher than in HS (41 g/m2,7). Peak systolic septal strain (21% vs 24% and 23%, p = 0.02) and midwall fractional shortening (16% vs 17% and 17%, p = 0.004) were significantly reduced in PA compared to both the other groups. No differences emerged as regards LV ejection fraction, peak longitudinal systolic septal tissue velocity and septal systolic strain rate. The indexes of diastolic filling (E/A ratio, DT and E/E’) did not differ between PA and SA. Conclusions: Hyperaldosteronism is associated with a prominent increase in LV mass and with related diastolic dysfunction. These changes imply a subclinical systolic dysfunction and appear to be related to raised total peripheral resistance in PA. At variance, in SA patients with liver cirrhosis, who have normal BP and reduced total peripheral resistance, they are related to the increased cardiac work deriving from underfilling. Whether the increased PRA contribute to this, remains to be clarified.

Plasma renin activity is a strong and independent prognostic indicator in patients with acute decompensated heart failure treated with renin-angiotensin system inhibitors.

The renin-angiotensin system (RAS) is activated in heart failure (HF) as a compensatory mechanism, being related to cardiac remodeling and poor prognosis. Although RAS inhibitors are used as first-line drugs for HF, plasma renin activity (PRA) is upregulated by RAS inhibitors via a negative feedback mechanism. The clinical significance of PRA during RAS inhibitor therapy is poorly understood in acute decompensated HF (ADHF). Therefore we examined the impact of PRA in HF patients already receiving RAS inhibitors. Of 611 consecutive patients with ADHF and emergency admission to hospital, we studied the impact of PRA on the prognosis of ADHF in 293 patients already receiving RAS inhibitors before admission. The patients were divided into 2 groups according to median PRA (≥ vs. <3.4 ng·ml(-1)·h(-1)). During a mean follow-up of 29.0 months, there were 124 deaths from all causes. Kaplan-Meier analysis showed that all-cause and cardiovascular mortality were significantly higher in patients with high PRA than low PRA (log-rank P=0.0002 and P<0.0001, respectively). Log PRA was an independent predictor of all-cause and cardiovascular death (HR, 1.194; 95% CI: 1.378-2.678, P<0.0001; and HR, 2.559; 95% CI: 1.610-4.144, P<0.0001, respectively). PRA was associated with an increased risk of all-cause and cardiovascular mortality in ADHF patients already receiving RAS inhibitors, suggesting that PRA would be a useful biomarker during ADHF treatment.

Two Cases with Pseudohypoaldosteronism

Pseudohypoaldosteronism type 1 PHA1 is characterized by salt loss which is due to peripheral resistance to aldosterone. Common clinical manifestations of PHA1 include hyponatremia, hyperkalemia, metabolic acidosis and elevated plasma aldosterone levels. The symptoms of PHA1 are easily confused with the symptoms of congenital adrenal hyperplasia associated with 21-hydroxylase deficiency or 3-beta-hydroxysteroid dehydrogenase deficiency; and the symptoms of hypoaldosteronism due to aldosterone deficiency. According to the clinical manifestations and Mendelian inheritance patterns, PHA1 can be classified as either renal PHA1 autosomal dominant or the more severe systemic PHA1 autosomal recessive . Herein, we presented two children with PHA1. Two children presented with vomiting, diarrhea, restlessness and dehydratation. After eliminating salt-losing congenital adrenal hyperplasia, PHA was diagnosed with high plasma renin activity and aldosterone

Plasma renin activity and its association with ischemic heart disease, congestive heart failure, and cerebrovascular disease in a large hypertensive cohort.

Plasma renin activity (PRA) may be a surrogate for vascular damage. The authors hypothesize that PRA is associated with cardiovascular and cerebrovascular disease (CED). A cross-sectional study (January 1, 1998, to December 31, 2009) was performed on hypertensive individuals 18 years and older using multivariable logistic regression models to estimate odds ratios (ORs) for ischemic heart disease (IHD), congestive heart failure (CHF), and CED based on PRA quartiles controlling for age, sex, race, diabetes mellitus (DM), and medication use. Among 7887 individuals (60% women; 34% whites, 23% blacks, and 19% Hispanics; and 29% with DM), the adjusted ORs (95% CI) for IHD were 0.94 (0.80-1.10), 1.09 (0.92-1.29), and 1.18 (1.00-1.39); for CHF were 1.23 (0.99-1.53), 1.27 (1.01-1.61), and 1.41 (1.13-1.77); and for CED were 0.95 (0.78-1.17), 0.77 (0.61-0.97), and 0.97 (0.78-1.20) for the second, third, and fourth quartiles compared with the first quartile. Higher PRA was associated with greater likelihood for prevalent IHD and CHF but not CED in this large ethnically diverse population of hypertensive individuals.