Dietary Sodium Restriction Research Articles

Dietary sodium intake restriction in patients with heart failure: an overview of systematic reviews.

This study aimed to identify, assess, and summarize systematic reviews on dietary sodium intake restrictions for patients with heart failure. Literature searches were conducted on Pubmed, CINAHL, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure, and the Wanfang Database up to January 2024. The methodological quality of the included reviews was assessed using the quality assessment tool from the Australian JBI Center for Evidence-Based Healthcare (2016). The results of systematic reviews and meta-analyses were synthesized and presented according to different outcome indicators. Nine systematic reviews were included in this study. The current evidence does not support the fact that dietary sodium intake restrictions for patients with heart failure have a positive impact on mortality rates, rehospitalization rates, and quality of life. Conversely, strict dietary sodium intake restrictions (≤ 2000mg/day) may increase the risk of death, rehospitalization, and symptom exacerbation. Dietary sodium intake restriction may not have a positive impact on clinical outcomes in patients with heart failure. Nevertheless, more evidence is required to explore the differences in the impact of various levels of dietary sodium restriction on the outcomes and symptom management indicators of patients with heart failure.

Rising Prevalence of Obesity and Primary Hyperaldosteronism: Co-incidence or Connected Circumstances Leading to Hypertension? A Narrative Review.

While obesity and its associated complications, mainly diabetes and hypertension, have been the largest public health problems of modern world, the emerging data suggests an increasing prevalence of primary hyperaldosteronism (PA) as one of the most common undiagnosed causes of hypertension. We believe that rising prevalence of PA in the era of high rates of obesity is likely not a chance finding but is deeply intersected with the rising rates of obesity. Higher serum aldosterone concentrations and urinary aldosterone excretion have been observed in patients with increased body mass index or larger waist circumference. The in vitro and pre-clinical studies suggest that adipocytes not only synthesize and secrete aldosterone but also release factors which stimulate production of aldosterone from adrenal glands. Aldosterone excess causing ligand-dependent activation of the mineralocorticoid receptor (MR) has increasingly been recognized as one of the important mechanisms of obesity-related hypertension. The aldosterone excess in these cases can be labelled as acquired hyperaldosteronism to differentiate it from the non-obesity related classical cases of PA. Because of serious consequences, recognizing aldosterone excess in obesity is important, as it gives a more compelling reason for weight loss and guidance to choosing pharmacotherapy wisely. Dietary sodium restriction and mineralocorticoid receptor antagonists play important roles in the management of PA associated with obesity.

Aerobic Exercise Training Protects Against Insulin Resistance, Despite Low-Sodium Diet-Induced Increased Inflammation and Visceral Adiposity.

Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (UNa) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce UNa, HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.

Dietary Sodium and Fluid Restriction for Patients with Heart Failure

Dietary Sodium and Fluid Restriction for Patients with Heart Failure

Impaired Saltiness Perception Contributes to Higher Sodium Intake Among Patients With Chronic Kidney Disease: A Cross-Sectional Two-Center Study

Dietary sodium restriction is important in the prognosis of patients with chronic kidney disease (CKD). The association between saltiness perception and sodium intake among CKD patients is unclear, and the factors that influence saltiness are also not fully understood. We evaluated saltiness perception in CKD patients employing a cost-effective saltiness perception test using sodium solutions and evaluated the association between saltiness perception, sodium intake, and the influencing factors. CKD outpatients not undergoing dialysis were enrolled from two medical centers and underwent saltiness perception tests together with 24-hour urine collections to measure daily sodium intake. Participants who perceived saltiness using the test solution containing 25mM sodium were regarded to have "preserved" saltiness perception, while those unable to perceive saltiness were regarded as having "impaired" saltiness perception. Of the total 132 participants, the median daily sodium intake was 3.36g (range; 0.51-9.95g/day), and 43 (32.6%) were ex- or current smokers. When participants were divided into 3 groups (G) according to daily sodium intake level: low (G1; 0.51-2.61g/day), middle (G2; 2.62-3.99g/day), and high (G3; 4.06-9.95g/day), there was an obvious difference in impaired saltiness perception between three groups: 6.8% in G1, 50.0% in G2 and 86.4% in G3 (P value=8.035 × 10-14, Cochran-Armitage test). In a multiple regression analysis in which the saltiness perception was adopted as a subjective variable, smoking habit (ex- or current smoker) and nonadherence to dietary sodium restriction were identified as significant explanatory variables. We revealed the clear relationship between higher daily sodium intake and impaired saltiness perception that is related to nonadherence to dietary sodium restriction and smoking habit, both of which could be intervened by nutritional counseling and public health education.

Dietary Sodium Intake and Outcomes: a Secondary Analysis From Sodium-HF

This post hoc analysis of SODIUM-HF (Study of Dietary Intervention under 100 mmol in Heart Failure) assessed the association between baseline dietary sodium intake and change at 6 months with a composite of cardiovascular (CV) hospitalizations, emergency department visits and all-cause death at 12 and 24 months. Dietary sodium restriction is common advice for patients with heart failure (HF). Randomized clinical trials have not shown a beneficial effect of dietary sodium restriction on clinical outcomes. A multivariable Cox proportional hazard regression model was used to assess the association of dietary sodium intake measured at randomization with primary and secondary endpoints. The study included 792 participants. Baseline sodium intake was ≤ 1500 mg/day in 19.9% (n = 158), 1501-3000 mg/day in 56.5% (n = 448) and > 3000 mg/day in 23.4% (n = 186) of participants. The factors associated with higher baseline sodium intake were higher calorie consumption, higher body mass index and recruitment from Canada. Multivariable analyses showed no association between baseline sodium intake nor magnitude of 6-month change or 12- or 24-month outcomes. In a responder analysis, participants achieving a sodium intake < 1500 mg at 6 months showed an association with a decreased risk for the composite outcome (adjusted HR 0.52 [95% CI 0.25, 1.07] P = 0.08) and CV hospitalization (adjusted HR 0.51 [95% CI 0.24, 1.09] P = 0.08) at 12 months. There was no association between dietary sodium intake and clinical outcomes over 24 months in patients with HF. Responder analyses suggest the need for further investigation of the effects of sodium reduction in those who achieve the targeted dietary sodium-reduction level.

Edema India: Executive Summary of Screening, Diagnosis, and Management of Edema.

The management of edema requires a systematic approach to screening, diagnosis, and treatment, with an essential initial assessment to differentiate between generalized and localized edema. The Association of Physicians of India (API) aimed to develop the first Indian Edema Consensus (Edema India), offering tailored recommendations for screening, diagnosing, and managing edema based on the insights from the expert panel. The panel suggested when evaluating edema symptoms, important factors to consider include the patient's current illness, medical history, risk factors, family history, and medications. Key diagnostic investigations for edema include complete blood count, cardiovascular imaging and markers, deep vein thrombosis (DVT) assessment, along with renal, hepatic, and thyroid function tests. Edema management involves a combination of pharmacologic and nonpharmacologic interventions, including limb elevation, physiotherapy, compression therapy, fluid removal, diuretics (loop diuretics: first-line therapy), and a sodium-restricted diet. The panel believed that educating patients could foster a preventive mindset, helping to prevent the worsening of edema.

Hold the salt for kidney regeneration.

The macula densa (MD) is a distinct cluster of approximately 20 specialized kidney epithelial cells that constitute a key component of the juxtaglomerular apparatus. Unlike other renal tubular epithelial cell populations with functions relating to reclamation or secretion of electrolytes and solutes, the MD acts as a cell sensor, exerting homeostatic actions in response to sodium and chloride changes within the tubular fluid. Electrolyte flux through apical sodium transporters in MD cells triggers release of paracrine mediators, affecting blood pressure and glomerular hemodynamics. In this issue of the JCI, Gyarmati and authors explored a program of MD that resulted in activation of regeneration pathways. Notably, regeneration was triggered by feeding mice a low-salt diet. Furthermore, the MD cells showed neuron-like properties that may contribute to their regulation of glomerular structure and function. These findings suggest that dietary sodium restriction and/or targeting MD signaling might attenuate glomerular injury.

Thirst symptoms in patients with heart failure: An integrative review.

To identify the risk and protective factors affecting thirst symptoms in patients with heart failure (HF) and intervention strategies to alleviate thirst symptoms. An integrative review. A total of 61 articles were retrieved. Screening yielded a total of 21 articles which were appraised for quality. The quality of studies was assessed using the Mixed Methods Appraisal Tool. Ten electronic databases were searched in October 2023, including Embase, Pubmed, CINAHL, Cochrane, Web of Science, Wiley, CNKI, VIP, CBM and WanFang. In addition, we searched grey databases and manually searched reference lists of included and relevant reviews. In total, 1644 articles were retrieved, of which 21 were included. Eight studies addressed the factors. Six themes emerged as risk factors, including demographics, severity of disease, psycho-environmental, medication, fluid restriction and homeostasis. Conversely, an increase in fluid intake, a high score of sodium restriction diet attitude and using ARB were identified as protective factors. Thirteen studies focus on intervention strategies. Five unique intervention strategies were identified, including Traditional Chinese Medicine, mint-related interventions, sour-flavour interventions, improved water restriction and cluster nursing strategy. This finding identified the factors associated with thirst symptoms in patients with HF, especially concerning the elaboration of risk factors, which suggests that healthcare professionals should focus on the risk factors for thirst in patients with HF and consciously avoid the occurrence of these risk factors. Additionally, there are considerable cultural differences in interventions, therefore, to increase adherence during symptom management, careful selection of appropriate intervention strategies based on the requirements and preferences of patients is required. While there are some therapies, there aren't enough high-quality empirical investigations. Thus, multi-centre, large-sample studies are also required in subsequent research to demonstrate the interventions' effectiveness. The nurse must notice the symptoms of thirst in HF to slow down the disease's progression and improve the patient's physical and emotional well-being. The review complies with the PRISMA guidelines for reporting systematic reviews. No patient or public contribution.

Revisiting resistant hypertension in kidney disease.

As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined. Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD. This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.

Chronic Kidney Disease Risk Awareness, Dietary Intake, and Food Security Among Black Male College Students

ObjectivesNutrition, lifestyle factors, and awareness of chronic kidney disease (CKD) risk are vital tools for preventing or delaying its development and progression in Black American (BA) males. Few published studies assess awareness of CKD risk in BA male college students despite being at high risk. This study aimed to 1) assess the awareness of CKD risk among BA male college students and 2) identify dietary and lifestyle habits related to CKD risk. MethodsThis was a cross-sectional online survey utilizing a network sampling technique. Inclusion criteria were self-identification as a Black American male and current enrollment in a university. Participants were recruited through publicly available social media sites and emails. The online questionnaire contained demographic, health status, and food security items. Pearson’s correlations explored associations between continuous variables; independent samples t-tests compared mean scores of responses between perceived risk of disease groups. ResultsSixty-seven participants completed the survey. Only 22.4% perceived they were at increased risk for kidney disease, while 49.3% felt at increased risk for developing hypertension (HTN). More respondents (32.8%) also felt at increased risk for developing diabetes than kidney disease. Dietary sodium restriction was reported by 34.3%, while only 14.9% had been advised to do so by a healthcare provider. Half of the respondents were deemed food insecure, and 17.86% were categorized as experiencing very low food security. ConclusionAwareness of CKD risk is low for BA male college students and lags behind awareness of HTN and diabetes risk. There may be a lack of knowledge regarding CKD as a long-term complication of HTN and diabetes. Dietary sodium restriction is marginal, and food security is a significant challenge in this high-risk group. Educational initiatives are needed to increase awareness of CKD risk among BA male college students.

Is dietary sodium restriction superior to regular diet in hospitalized patients with heart failure to decrease length of stay?

Is dietary sodium restriction superior to regular diet in hospitalized patients with heart failure to decrease length of stay?

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC.

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion.

Dietary Sodium Restriction and Frailty among Middle-Aged and Older Adults: An 8-Year Longitudinal Study.

Frailty is a common geriatric syndrome. However, there is little information about the relationship between dietary sodium restriction (DSR) and frailty in later life. This study aimed to elucidate the relationship between DSR and frailty in middle-aged and older adults. The 8-year follow-up data from the Taiwan Longitudinal Study on Aging, including 5131 individuals aged ≥50 years, were analyzed using random-effects panel logit models. DSR was evaluated by assessing whether the participants were told by a physician to reduce or avoid sodium intake from food. Three indices were used to measure frailty: the Study of Osteoporotic Fractures (SOF) index, the Fried index, and the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) index. Individuals with DSR were more likely to report frailty compared with those with non-DSR (SOF: adjusted odds ratio [AOR] = 1.82, 95% confidence interval [CI] = 1.46-2.27; Fried: AOR = 2.55, 95% CI = 1.64-3.98; FRAIL: AOR = 2.66, 95% CI = 1.89-3.74). DSR was associated with a higher likelihood of SBF (AOR = 2.61, 95% CI = 1.61-4.22). We identified a temporal trajectory in our study, noting significant participant reactions to both short- and mid-term DSR. Future research should address the balance between frailty risk and cardiovascular risk related to DSR.

Psychometric properties of the Iranian version of the thirst distress scale and dietary sodium restriction questionnaire for the elderly with heart failure.

Recognizing thirst distress and sodium intake restriction using valid and reliable tools enable evidence-based care, and improve treatment outcomes for the elderly with heart failure (HF). The present study investigated the psychometric properties of the thirst distress scale (TDS-HF) and dietary sodium restriction questionnaire for Iranian's elderly with HF (DSRQ-HF). This crossectional study was conducted during 2021-2022. Two hundred and forty elderly people referring to the cardiology clinics and offices in the western region of Mazandaran, Iran were selected by the convenient sampling method. First, the two questionnaires were translated. Then, face, content, and construct validity were assessed. Several indices were used to evaluate, including the chi-square/degree-of-freedom ratio (CMIN/DF), parsimonious normed fit index (PNFI), comparative fit index (CFI), parsimonious comparative fit index (PCFI). The value of content validity index of all items of the two questionnaires was higher than 0.62. The fit indices, including PCFI=0.594, PNFI=0.582, CMIN/DF=1.987, and CFI=0.979, confirmed the one-factor construct of TDS. PCFI=0.724, PNFI=0.661, CMIN/DF=1.935, ad CFI=0.905, indicated the confirmation of the three-factor construct of DSRQ. The value of Cronbach's alpha of the two questionnaires were 0.86. The value of Ω of the TDS-HF and DSRQ-HF were 0.858, and 0.860, respectively. The value of θ of the TDS-HF and DSRQ-HF were 0.858, and 0.861, representing the suitability of both constructs. The TDS-HF and DSRQ-HF can be used to measure the psychometric effects of diet therapy and behaviors of the elderly with HF in relation to adherence to diet therapy.

Dietary sodium intake and outcomes: a secondary analysis from SODIUM - HF

Abstract Background Sodium restriction is common advice provided to patients with heart failure, however, evidence from the SODIUM-HF trial and a subsequent meta-analysis failed to show a beneficial effect of dietary sodium restriction on outcomes. Purpose This secondary analysis of SODIUM HF is aimed to assess association between baseline dietary sodium intake, the change in dietary sodium at 6 months and a composite of cardiovascular hospitalization, emergency department visit, and all-cause death at 12 and 24 months. Methods Multivariable Cox proportional hazard regression model was used to assess association of dietary sodium level measured at randomization with primary and secondary endpoints. Adjusted Hazard ratios and 95% confidence intervals were presented. A responder analysis also explored the achieved dietary sodium at 6 months with subsequent risk for clinical outcomes. Results 792 participants were included. At baseline, sodium intake was ≤ 1500 mg/day in 19.9% (n = 158), &amp;gt;1500-3000 mg/day in 56.5% (n = 448) and &amp;gt;3000 mg/day in 23.4% (n= 186) of the participants. Women, older patients, and those with lower glomerular filtration rate and higher ejection fraction were more often represented in the group with sodium intake ≤1500 mg/day; conversely, diabetes, prior smoking, use of mineralocorticoid receptor antagonists, and ICD were observed in the groups of higher sodium intake levels (&amp;gt;3000 mg/day)(Table 1). Cox proportional hazard regression analysis showed no association between sodium level (per doubling) at baseline with clinical outcomes (all associations p=ns), however, adjusted models exhibited a trend towards a decreased risk of CV hospitalizations at 2 years. In the responder analysis, a trend towards a decreased adjusted risk for composite outcome and CV hospitalizations at 1 year in those achieving a sodium level &amp;lt;1500 mg at 6 months was observed (Table 2). Adjusted Cox proportional hazard regression analysis showed no association for 1- and 2-year outcomes per 500 mg increase in absolute difference in sodium level between baseline and 6 months. Conclusion In SODIUM HF, there was no association between sodium level at baseline with clinical outcomes at any time point but there is a trend towards a decreased risk of CV hospitalizations at 2 years and in patients achieving &amp;lt;1500 mg / day by 6 months, a trend towards fewer subsequent clinical events was present. This finding should be explored via a prospective clinical trial.Baseline characteristics of populationOutcomes

Abstract 15250: Increased CD81 is Associated With Enhanced Apoptosis in Acute Kidney Injuries Induced by Candesartan/Low Salt Diet

Introduction: Our previous studies have demonstrated that the upregulation of renal CD81 (cluster of differentiation 81), contributes to the sustained hypertension observed in LPS-preeclampsia rats with kidney injuries. Candesartan (Can) lowers blood pressure by selectively blocking type 1 angiotensin II receptors and results in acute kidney injury (AKI) when used together with dietary sodium restriction. Various cell deaths including apoptosis and necrosis are involved in the pathogenesis of AKI. Hypothesis: Renal CD81 may increased in candesartan/low salt diet(LS+Can) model via activation of apoptosis. Methods: Male SD rats aged 8-10 weeks were fed with LS (0.01% NaCl) or normal salt diets (NS, 0.8% NaCl) (6-10rats/group) respectively for 7 days.All rats were intraperitoneally injected with candesartan (1mg/kg/d) simultaneously.Systolic blood pressure(SBP) was monitored with tail-cuff method.The rats were sacrificed by over-anesthesia after the samples of blood and urine (metabolic cage) were collected.The kidneys were immediately removed for immunoblotting, and TUNEL(TdT-mediated dUTP Nick-End Labeling) measurements.P&lt;0.05 was considered significant for 2 group comparison with t-test. Results: Compared with rats on NS+Can, the serum creatinine (20.3±0.3 vs 50.8±4.2 mmol/L) and BUN(4.05±0.2 vs 18.6±2.5 mmol/L) were more than doubled in LS+Can rats ;Creatinine clearance was decreased (100±4.1 vs 40.8±3.7ml/min); systolic blood pressures was lowered slightly (101.7±1.7 vs 88.9±2.7mmHg, n=7-8). Renal CD81 protein abundance by immunoblotting was increased (258.8±52.4,% of control, n=6/group,p&lt;0.05, same as below).At the same time, there were increases in apoptosis-associated proteins including bax(312.6±71.5),caspase-3(124.6±6) ,cleaved caspase3(133.8±9.6) in Can+LS group.The rate of tunel-positive cells was elevated in the Can+LS group. (100.0±8.5 vs 482.72±59.4,p&lt;0.05,n=10/group).However, necrosis-related inflammatory factors, including Interleukin-6,tumor necrosis factor-α, were not affected in the rat kidneys from LS+Can treated rats. Conclusions: Our findings suggest that Increased CD81 may be associated with enhanced apoptosis in rat kidneys with acute kidney injuries.

Is increased subjective thirst associated with greater interdialytic weight gains, extracellular fluid and dietary sodium intake?

Some previous studies have reported an effect of increasing subjective thirst and interdialytic weight gains (IDWG), and that this may be influenced by nonadherence to dietary sodium restrictions, whereas others reported no such association. As such we wished to review the effect of self-reported thirst on IDWGs and dietary sodium intake. Dialysis patients were asked to complete visual analogues thirst, distress thermometer (DT) scores and complete a sodium food frequency questionnaire (SFFQ). IDWG and pre and post dialysis volumes were measured with multifrequency bioelectrical impedance. One hundred and eleven patients completed the questionnaires and had bioimpedance measurements: 63% male, mean age 63.8 ± 16.1 years, 33% diabetic with a median thirst score 3 (0-5) and SFFQ 52.0 ± 18, and IDWG 2.1 ± 1.3%. Thirst was associated with DT (r = 0.28, p = 0.004) and negatively with age (r = -0.31, p < 0.001), but not SFFQ, IDWG, extracellular water, or dialysate sodium, or dialysate to plasma gradient. Patients with higher thirst scores were younger (58.0 ± 15.2 vs. 69.4 ± 15.0 years, p < 0.001) with higher DT scores (5 [2-7] vs. 2 [0-5], p < 0.001). On multivariate logistic analysis, only age was associated with self-reported thirst (odds ratio 0.95, 95% confidence limits 0.92-0.98, p < 0.001). We found that subjective thirst was greater for younger patients and those who reported higher levels of distress, but no association with IDWGs, dietary sodium intake, or dialysate sodium. However, most of our patients followed the dietary advice, as evidenced by the low SFFQ scores and % IDWGs. Whether thirst increases distress or distress increases subjective thirst remains to be determined.

CACNA1D Gene Polymorphisms Associate With Increased Blood Pressure and Salt Sensitivity of Blood Pressure in White Individuals.

Disease-causing mutations in CACNA1D gene occur in aldosterone-producing adenomas and familial hyperaldosteronism. We determined whether single nucleotide polymorphisms in CACNA1D gene associate with higher aldosterone resulting in salt sensitivity of blood pressure (BP) and increased BP in men and women. Data were obtained from the HyperPATH (International Hypertension Pathotypes) cohort, where participants completed a cross-over intervention of liberal and restricted sodium diets. Multi-Ethnic Genotyping Array identified 104 CACNA1D single nucleotide polymorphisms that met quality control. Single nucleotide polymorphism is rs7612148 strongly associated with systolic BP and was selected for study in 521 White participants in 3 scenarios ([1] hypertensives; [2] normotensives; [3] total population=hypertensives+normotensives) using multivariate regression analysis. In the total population and hypertensives, but not normotensives, risk allele carriers (CC, GC), as compared with nonrisk allele homozygotes (GG), exhibited higher salt sensitivity of BP and, on liberal sodium diet, higher systolic BP, lower baseline and angiotensin II-stimulated aldosterone, and lower plasma renin activity. On restricted sodium diet, BP was similar across genotypes, suggesting sodium restriction corrected/neutralized the genotype effect on BP. Because increased aldosterone did not seem to drive the increased salt sensitivity of BP and increased BP on liberal sodium diet, we assessed renal plasma flow. Renal plasma flow increase from restricted to liberal sodium diets was blunted in risk allele homozygotes in the total population and in hypertensives. A replication study in another cohort HyperPATH B (International Hypertension Pathotypes Cohort B) confirmed BP-genotype associations. CACNA1D rs7612148 risk allele associated with increased BP and salt sensitivity of BP, likely due to an impaired ability to increase renal plasma flow in response to a liberal sodium diet and not to excess aldosterone.

FRI153 Genetic Variant In Armadillo Repeat Containing 5 Gene (ARMC5) Associates With Salt Sensitivity Of Blood Pressure And Aldosterone In A Caucasian Cohort

Abstract Disclosure: W.W. Parksook: None. M. Heydarpour: None. L. Pojoga: None. A. Gaye: None. G.H. Gibbons: None. G.H. Williams: Advisory Board Member; Self; Cereno. Consulting Fee; Self; Alnylam, Crinetics, Damian, KBP bioscience, Paxel, Relapsa, Unicycive. Grant Recipient; Self; NIH 2 grants. J.S. Williams: Advisory Board Member; Self; Mellicell, Inc. Background: Genetic alterations of ARMC5 have been reported in various adrenal disorders, particularly in primary bilateral macronodular adrenal hyperplasia. Increasing evidence shows that polymorphic variants in ARMC5 are also associated with blood pressure (BP), hypertension, and the renin-angiotensin-aldosterone-system (RAAS) in individuals of African descent; however, little is known about these relationships in Caucasians. Herein, we conducted a deep phenotyping study to assess the association of ARMC5 variants with BP, salt sensitivity of BP (SSBP), and components of the RAAS in Caucasians. Methods: Normotensive and hypertensive, non-diabetic, non-chronic kidney disease, Caucasian participants underwent two dietary interventions at 5-7 days apart (200 mmol/day and 10 mmol/day sodium) to assess SSBP and other hormonal parameters. All participants were genotyped using a Multi-Ethnic-Genotyping-Array. Association analysis and the quality control of the genomic data were assessed by PLINK. Participants with complete data for SSBP and hormonal parameters, who were in salt balance, were included in the analysis (n= 306). Multiple linear regression models were used to assess the association between the genetic variant and outcome parameters. Results: There were 5 single nucleotide polymorphisms in the ARMC5 region. rs4889660 was significantly associated with SSBP in additive and dominant models when adjusted by Bonferroni correction. In a candidate gene analysis, rs4889660 risk allele carriers had greater SSBP than non-risk allele homozygotes (β= 4 mmHg, P= 0.03). Following dietary sodium restriction, rs4889660 risk allele carriers had lower serum aldosterone levels in an upright position (β= -6.9 ng/dl, P= 0.04) and serum aldosterone levels after angiotensin II stimulation (β= -3.0 ng/dl, P= 0.02). There were no differences between plasma renin activity, serum and urinary cortisol levels, and renal plasma flows between genotypes. Conclusions: There was an association between the ARMC5 rs4889660 variant and SSBP in Caucasians. With dietary sodium restriction, aldosterone responses to both upright posture and angiotensin II infusion were lower in the risk allele carriers. The reduced aldosterone responses suggest that an alteration in the RAAS system is not the cause of the SSBP, but is in response to a defect in another sodium-mediated homeostatic mechanism. Presentation: Friday, June 16, 2023