High Salt Intake Is Independently Associated With Hypertensive Target Organ Damage

Background: The prevalence of hypertension and blood pressure-related target organ damage in African-Americans is among the highest in the world. We hypothesize that this is in part due to aldosterone dysregulation among African-Americans beginning in youth and leading to the early development of cardiovascular disease in this population. To begin to test this hypothesis, we examined ethnic differences in aldosterone regulation in normal, healthy adolescents. Methods: The subjects in this study were 145 (60 Caucasian, 85 African-American) healthy, normotensive youth aged 15–19 years. Testing was performed following 72 hours on a controlled sodium diet. Testing consisted of the collection of aldosterone, systolic blood pressure (SBP), and urinary sodium excretion (U Na V) during continuous water intake (400 ml total) over a 2 hour period. An echocardiogram was also performed to measure target organ changes. Log transformations were performed on aldosterone levels prior to analyses. Results: African-American compared to Caucasian subjects had higher casual SBP (109±10 v 104±10; p=.006) and relative wall thickness (0.32±.03 v 0.34±.04; p=.003). During the testing procedure African-Americans also had lower levels of aldosterone (4.78±.6 v 4.35±.6 pg/ml; p =.001). In the Caucasian subjects only, aldosterone was inversely correlated with U Na V (r=−0.427; p=.001) and U Na V was positively correlated with SBP (r=0.356; p=.001). The subjects were divided into those in the upper and lower quartiles of salt intake for further analysis. The interaction between race and salt intake was significant for aldosterone (F=7.173; p=.008). Caucasian subjects with high salt intake had lower aldosterone (4.56±.59 v 5.02±0.59 pg/ml). However, aldosterone levels did not differ by salt intake in African-Americans. Summary and Conclusion: African-American subjects did not show the expected associations between aldosterone and the pressure natriuresis relation. Furthermore, African-Americans on the high salt intake failed to suppress aldosterone. These findings are consistent with our hypothesis that aldosterone dysregulation in youth may lead to the early development of cardiovascular disease in Africans-Americans.

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AT1receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00737.2007 ◽

2008 ◽

Vol 294 (2) ◽

pp. H853-H858 ◽

Cited By ~ 59

Author(s):

Jasmina Varagic ◽

Edward D. Frohlich ◽

Dinko Susic ◽

Jwari Ahn ◽

Luis Matavelli ◽

...

Keyword(s):

Angiotensin Ii ◽

Arterial Pressure ◽

Myocardial Fibrosis ◽

Salt Intake ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Target Organ ◽

Dietary Salt ◽

High Salt Intake

Our recent studies have demonstrated that salt excess in the spontaneously hypertensive rat (SHR) produces a modestly increased arterial pressure while promoting marked myocardial fibrosis and structural damage associated with altered coronary hemodynamics and ventricular function. The present study was designed to determine the efficacy of an angiotensin II type 1 (AT1) receptor blocker (ARB) in the prevention of pressure increase and development of target organ damage from high dietary salt intake. Eight-week-old SHRs were given an 8% salt diet for 8 wk; their age- and gender-matched controls received standard chow. Some of the salt-loaded rats were treated concomitantly with ARB (candesartan; 10 mg·kg−1·day−1). The ARB failed to reduce the salt-induced rise in pressure, whereas it significantly attenuated left ventricular (LV) remodeling (mass and wall thicknesses), myocardial fibrosis (hydroxyproline concentration and collagen volume fraction), and the development of LV diastolic dysfunction, as shown by longer isovolumic relaxation time, decreased ratio of peak velocity of early to late diastolic waves, and slower LV relaxation (minimum first derivative of pressure over time/maximal LV pressure). Without affecting the increased pulse pressure by high salt intake, the ARB prevented the salt-induced deterioration of coronary and renal hemodynamics but not the arterial stiffening or hypertrophy (pulse wave velocity and aortic mass index). Additionally, candesartan prevented the salt-induced increase in kidney mass index and proteinuria. In conclusion, the ARB given concomitantly with dietary salt excess ameliorated salt-related structural and functional cardiac and renal abnormalities in SHRs without reducing arterial pressure. These data clearly demonstrated that angiotensin II (via AT1receptors), at least in part, participated importantly in the pressure-independent effects of salt excess on target organ damage of hypertension.

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Prevalence, Biochemical and Clinical Characteristics of Resistant Hypertension

Revista de Chimie ◽

10.37358/rc.18.10.6637 ◽

2018 ◽

Vol 69 (10) ◽

pp. 2845-2849

Author(s):

Daniela Gurgus ◽

Elena Ardeleanu ◽

Carmen Gadau ◽

Roxana Folescu ◽

Ioan Tilea ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Resistant Hypertension ◽

Clinical Characteristics ◽

Salt Intake ◽

Target Organ Damage ◽

Multivariate Logistic Regression Analysis ◽

Organ Damage ◽

Left Ventricular ◽

High Salt Intake

The objectives of the present study were to evaluate the prevalence of resistant hypertension (RH) in primary care setting and to analyse its biochemical and clinical characteristics. After 3 months of treatment and evaluation, 721 (14.01%) of 5,146 patients with hypertension did not reach target office blood pressure of [ 140/90 mmHg. After exclusion of �white-coat effect� with ambulatory blood pressure, of secondary and pseudo- resistant hypertension, prevalence of RH was 6.74%. Lifestyle factors associated with RH were physical inactivity, obesity, high salt intake, smoking and excessive alcohol ingestion. Compared to controlled hypertension, RH patients presented higher incidence of family history of cardiovascular disease (38.90% vs 25.94%), diabetes mellitus (34.87% vs 19.01%), impaired fasting glucose (21.91% vs 19.07%), target organ damage (29.1% vs 15.95%), and cardiovascular disease (27.09% vs 17.06%). Dyslipidaemia (52.90% vs 42.03%), fasting plasma glucose (116.10�38.9 vs 107.80�37.2), HbA1c (6.41�1.42 vs 5.96�0.94), serum creatinine (1.09�0.27 vs 1.03�0.24) and microalbuminuria (21.90% vs 10.95%) were significantly higher in RH. Predictors of RH, determined by a multivariate logistic regression analysis were left ventricular hypertrophy (OD 2.14, 95% CI 1.32-3.69), renal impairment expressed as eGFR [ 60 ml/min/1.73m2 (OD 1.62, 95% CI 1.21-2.21) and the presence of cardiovascular disease (OD 1.48, 95% CI 1.02-2.16).

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Inappropriate activity of local renin-angiotensin-aldosterone system during high salt intake: impact on the cardio-renal axis

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-3661 ◽

2018 ◽

Vol 40 (2) ◽

pp. 170-178 ◽

Cited By ~ 4

Author(s):

Sabrina Ribeiro Gonsalez ◽

Fernanda Magalhães Ferrão ◽

Alessandro Miranda de Souza ◽

Jennifer Lowe ◽

Lucienne da Silva Lara Morcillo

Keyword(s):

Observational Studies ◽

Salt Intake ◽

Organ Damage ◽

High Salt ◽

Public Health Issue ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

High Salt Intake ◽

Reduced Salt ◽

The Impact

ABSTRACT Although there is a general agreement on the recommendation for reduced salt intake as a public health issue, the mechanism by which high salt intake triggers pathological effects on the cardio-renal axis is not completely understood. Emerging evidence indicates that the renin-angiotensin-aldosterone system (RAAS) is the main target of high Na+ intake. An inappropriate activation of tissue RAAS may lead to hypertension and organ damage. We reviewed the impact of high salt intake on the RAAS on the cardio-renal axis highlighting the molecular pathways that leads to injury effects. We also provide an assessment of recent observational studies related to the consequences of non-osmotically active Na+ accumulation, breaking the paradigm that high salt intake necessarily increases plasma Na+ concentration promoting water retention

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Mapping and confirmation of a major left ventricular mass QTL on rat chromosome 1 by contrasting SHRSP and F344 rats

Physiological Genomics ◽

10.1152/physiolgenomics.00067.2013 ◽

2013 ◽

Vol 45 (18) ◽

pp. 827-833 ◽

Cited By ~ 1

Author(s):

Katja Grabowski ◽

Gerold Koplin ◽

Bujar Aliu ◽

Leonard Schulte ◽

Angela Schulz ◽

...

Keyword(s):

Salt Intake ◽

Target Organ Damage ◽

Left Ventricular ◽

High Salt ◽

Chromosome 1 ◽

Dietary Salt ◽

A Genome ◽

High Salt Intake ◽

Lv Mass ◽

Major Qtl

An abnormal increase in left ventricular (LV) mass, i.e., LV hypertrophy (LVH), represents an important target organ damage in arterial hypertension and has been associated with poor clinical outcome. Genetic factors are contributing to variation in LV mass in addition to blood pressure and other factors such as dietary salt intake. We set out to map quantitative trait loci (QTL) for LV mass by comparing the spontaneously hypertensive stroke-prone (SHRSP) rat with LVH and normotensive Fischer rats (F344) with contrasting low LV mass. To this end we performed a genome-wide QTL mapping analysis in 232 F2 animals derived from SHRSP and F344 exposed to high-salt (4% in chow) intake for 8 wk. We mapped one major QTL for LV mass on rat chromosome 1 (RNO1) that demonstrated strong linkage (peak logarithm of odds score 8.4) to relative LV weight (RLVW) and accounted for ∼19% of the variance of this phenotype in F2 rats. We therefore generated a consomic SHRSP-1F344 strain in which RNO1 from F344 was introgressed into the SHRSP background. Consomic and SHRSP animals showed similar blood pressures during conventional intra-arterial measurements, while RLVW was already significantly lower (−17.7%, P < 0.05) in SHRSP-1F344 in response to a normal-salt diet; a similar significant reduction of LV mass was also observed in consomic rats after high-salt intake ( P < 0.05 vs. SHRSP). Thus, a major QTL on RNO1 was confirmed with significant impact on LV mass in the hypertensive background of SHRSP.

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Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism

Hormone and Metabolic Research ◽

10.1055/a-1116-2407 ◽

2020 ◽

Vol 52 (06) ◽

pp. 386-393

Author(s):

Christian Adolf ◽

Holger Schneider ◽

Daniel A. Heinrich ◽

Laura Handgriff ◽

Martin Reincke

Keyword(s):

Cardiovascular Risk ◽

Primary Aldosteronism ◽

Salt Intake ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

World Health ◽

Salt Appetite ◽

Dietary Salt ◽

Dietary Salt Intake

AbstractFirst described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5–10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk.

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