High Sodium Diet Research Articles

Ketosis, Salt, and Water: Novel Mechanistic Insights into Diet and Mineralocorticoid Metabolism.

The association between dietary macronutrient composition and cardiovascular health has been studied extensively for decades (1, 2). High dietary sodium intake has traditionally been linked with cardiovascular disease and mortality, although recent data suggest that this association may be negligible where mean intake is less than 5 g/day. The renin-angiotensin-aldosterone system (RAAS) is a key regulator of circulating blood volume, as well as sodium and potassium homeostasis. Renin production from the renal juxtaglomerular apparatus is stimulated by reduced circulating blood volume, thereby stimulating aldosterone secretion from zona glomerulosa cells of the adrenal cortex. Primary aldosteronism, due to a unilateral aldosterone-producing adenoma (Conn's syndrome) or bilateral hyperplasia of the glomerulosa, is an important cause of secondary hypertension and has independent associations with cardiovascular disease (3). In the absence of autonomous aldosterone production, antagonism of the mineralocorticoid receptor is a key therapeutic approach in hypertension and heart disease by lowering blood pressure and improving cardiac remodeling.

The global, regional, and national burden of stomach cancer among adolescents and young adults in 204 countries and territories, 1990-2019: A population-based study.

Stomach cancer is a significant health problem in many countries. But healthcare needs of adolescents and young adults (AYAs) stomach cancer patients have been historically neglected. An accurate appraisal of the burden of AYA stomach cancer is crucial to formulating effective preventive strategies. In this study, we report the most recent estimates of AYA stomach cancer burden concerning socio-demographic index (SDI) in 204 countries and territories between 1990 and 2019. Estimates from the Global Burden of Disease study 2019 were used to analyze incidence, mortality, and disability-adjusted life years (DALYs) due to AYA stomach cancer at global, regional, and national levels. Association between AYA stomach cancer burden and SDI were investigated. All estimates are reported as absolute numbers and age-standardized rates, which were standardized to the GBD world population and reported per 100,000 population. In 2019, there were 49,000 incident cases, 27,895 deaths, and 1.57 million DALYs due to AYA stomach cancer globally. The highest age-standardized incidence rate occurred in East Asia [2.42 (women) and 4.71 (men) per 100,000 person-years] and high-income Asia Pacific [3.16 (women) and 2.61 (men) per 100,000 person-years]. Age-standardized death [1.53 (women) and 2.65 (men) per 100,000 person-years] and DALY [150.96 (women) and 87.13 (men) per 100,000 person-years] rates were highest in Oceania. Compared with 1990, in 2019 more than 1,075 more incident cases of AYA stomach cancer were estimated with a decrease of 7,784 deaths. Despite the increase in absolute number of incident cases, the worldwide age-standardized rates of AYA stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with an improved SDI. Globally, 24.41% of the age-standardized DALYs were attributable to a high-sodium diet in both sexes combined, and 0.57% of the age-standardized DALYs were attributable to smoking in men. The global burden of AYA stomach cancer is substantial, especially in developing regions. Capacity-building activities for AYA stomach cancer will benefit the younger generation and population health worldwide.

High Dietary Sodium, Measured Using Spot Urine Samples, is Associated with Higher Blood Pressure among Young Adults in Haiti.

Hypertension (HTN) is the leading cardiovascular disease (CVD) risk factor in Haiti and is likely driven by poverty-related social and dietary factors. Salt consumption in Haiti is hypothesized to be high but has never been rigorously quantified. We used spot urine samples from a subset of participants in the population-based Haiti Cardiovascular Disease Cohort to estimate population mean daily sodium intake. We compared three previously validated formulas for estimating dietary sodium intake using urine sodium, urine creatinine, age, sex, height, and weight. We explored the association between dietary sodium intake and blood pressure, stratified by age group. A total of 1,240 participants had spot urine samples. Median age was 38 years (range 18-93), and 48% were female. The mean dietary sodium intake was 3.5-5.0 g/day across the three estimation methods, with 94.2%-97.9% of participants consuming above the World Health Organization (WHO) recommended maximum of 2 g/day of sodium. Among young adults aged 18-29, increasing salt intake from the lowest quartile of consumption (<3.73 g/day) to the highest quartile (>5.88 g/day) was associated with a mean 8.71 mmHg higher systolic blood pressure (SBP) (95% confidence interval: 3.35, 14.07; p = 0.001). An association was not seen in older age groups. Among participants under age 40, those with SBP ≥120 mmHg consumed 0.5 g/day more sodium than those with SBP <120 mmHg (95% confidence interval: 0.08, 0.69; p = 0.012). Nine out of 10 Haitian adults in our study population consumed more than the WHO recommended maximum for daily sodium intake. In young adults, higher sodium consumption was associated with higher SBP. This represents an inflection point for increased HTN risk early in the life course and points to dietary salt intake as a potential modifiable risk factor for primordial and primary CVD prevention in young adults.

Validation of spot urine in estimating 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets in healthy adults

Purpose To evaluate the validity of spot urine assay methods in estimating the 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets. Materials and methods Twelve healthy volunteers were asked to adhere to 3 dietary sodium targets (3.3–5.0g/day,<3.3 g/day and >5.0 g/day) for three consecutive weeks and to measure salt excretion daily in spot urine samples using a self-monitoring device. On day 7 of each week, 24-h urine was collected to compare measured with estimated 24-h salt excretion (by the Kawasaki, Tanaka and INTERSALT equations). Results Correlation coefficients relating measured and estimated 24-h sodium excretion were low and not significant for Kawasaki and INTERSALT and moderate for the Tanaka equation (τ 0.56–0.64,p<.05). Bland–Altman plots showed considerable differences between estimated and measured sodium excretion across all salt diets. Over 40% of the participants showed an absolute difference between measured and estimated 24-h sodium of more than 1000 mg/day. The correlation coefficients between 24-h and spot Na/K ratio were 0.67, 0.94 and 0.85(p<.05), and mean differences were 0.59, 0.06 and 0.48 for the intermediate, low and high sodium diets, respectively. Conclusion These findings do not support estimation of individual 24-h salt excretion from spot urine by the Kawasaki, Tanaka, or INTERSALT formula.

Short exposure to high salt in drinking solution leads to a cardiovascular phenotype of hypertension without changes in the blood volume of rats.

What is the central question of this study? Is the cardiovascular phenotype of high blood pressure observed in rats salt loaded with 2% NaCl in drinking solution a blood volume-dependent hypertension? What is the main finding and its importance? Animals exposed to 2% NaCl drinking solution develop hypertension, with dominance of sympathetic outflow and high [Na+ ] in the cerebrospinal fluid, but without changes in the blood volume. The phenotype of salt-dependent hypertension might be related to accumulation of [Na+ ] in the cerebrospinal fluid, which makes it an interesting animal model in which to study the neuronal pathways involved in control of the circulation in osmotic challenge conditions. Evidence suggests that hypertension induced by high salt intake is correlated with an autonomic imbalance that favours sympathetic hyperactivity and an increase in vascular resistance, indicating a neurogenic component to this pathology. Although there are several animal models in which to study salt-induced hypertension with prolonged exposure to a high-sodium diet, here we sought to investigate whether the increase in arterial blood pressure of rats subjected to a short exposure to high salt, with 2% NaCl drinking solution instead of water, relies on changes in the circulating blood volume. Male Wistar rats were divided randomly into three groups: euhydrated (EU, n=10), salt loaded (SL, n=13) and water deprived (WD, n=6). The SL rats exhibited a significant increase in mean arterial blood pressure, with a large low-frequency component of systolic arterial blood pressure variability, when compared with the EU group. Circulating blood volume did not differ between SL and EU rats, but it was lower in WD rats. Compared with EU rats, the [Na+ ] in cerebrospinal fluid was higher in SL rats and similar in magnitude to the WD rats. Plasma [Na+ ] did not differ between SL and EU rats, but it was higher in WD rats. Collectively, our data suggest that the hypertension induced by a short exposure to high salt intake closely resembles a neurogenic mechanism, but not a blood volume-dependent mechanism, with cumulative [Na+ ] in the cerebrospinal fluid that could be associated with changes in the neurochemistry of autonomic nuclei, which are highly susceptible to osmotic stress related to high salt consumption.

Antioxidant activity and phytochemical analysis of fennel seeds and flaxseed.

Natural herbs are now receiving more attention due to the growing demand for their antioxidant properties. This study compared flaxseed and fennel seeds for their nutritional composition, bioactive moieties, and antioxidant activity-the study comprised two different phases. According to methods, phase I analyzed flaxseed and fennel seeds for proximate composition, mineral profile, dietary fiber, and amino acid content. In phase II, seeds were extracted using three different solvents, i.e., ethanol 80%, acetone 80%, and distilled water, to probe the total phenolic and flavonoid content. Antioxidant activity was measured using DPPH and a FRAP in the final phase. Current study revealed that flaxseed had higher protein (17.33 ± 0.02%), fat content (36.76 ± 0.02%), potassium (763.66 ± 4.04 mg/100 g), iron (5.13 ± 0.03 mg/100 g), phosphorus (581.46 ± 4.07 mg/100 g), magnesium (406.60 ± 5.12 mg/100 g), and zinc (3.30 ± 0.49 mg/100 g), respectively. In fennel seed, high dietary fiber (53.2 ± 0.01 g/100 mg), calcium, manganese, and sodium (588.93 ± 7.77, 20.30 ± 0.95, and 57.34 ± 0.33 mg/100 g, respectively) were found. Acetone showed better extraction efficiency than acetone, ethanol, and distilled water. Moreover, acetone flaxseed extract showed higher total phenolic content (84.13 ± 7.73 mgGAE/g), flavonoid content (5.11 ± 1.50 mgQE/g), and FRAP (5031 ± 15.92 μMFe2+/g) than fennel seed extract. This study showed that, among both herbs, flaxseed extract may have pharmacological potential in preventing illnesses and may be suggested for use in the food industry as a natural antioxidant.

Changing trends of the disease burden of non-rheumatic valvular heart disease in China from 1990 to 2019 and its predictions: Findings from global burden of disease study.

China has an increasing burden of non-rheumatic valvular heart disease (NRVHD) as the aging of the population is deepening. The aim was to assess the age and sex-specific prevalence and DALYs of NRVHD in China from 1990 to 2019 and to predict the burden in the next 25 years. The Global Burden of Disease Study (2019) was used to extract the data of age- and sex-specific incidence, mortality, and disability-adjusted life years (DALYs) of NRVHD in China, 1990-2019. We estimated the annual percentage change (EAPC) to access the temporal trends of the disease burden of NRVHD. The R package called Nordpred was used to perform an age-period-cohort analysis to predict the prevalence of NRVHD in the next 25 years. The number of incident cases of NRVHD increased from 93.16 thousand in 1990 to 325.05 thousand in 2019. Overall upward trends were observed in the age-standardized incidence rate (ASIR) from 1990 to 2019. Significant temporal trends in mortality and DALYs of NRVHD were observed. High systolic blood pressure, high sodium diet, and lead exposure were the main driving forces for NRVHD. In the next 25 years, the number of new cases and deaths of NRVHD should continue to increase to 390.64 thousand and 10.0 thousand, respectively. The ASIR should show an upward trend, while the ASMR should show a downward trend among men and women. In China, the overall rates of NRVHD have increased over the past 30 years, and there has been a substantial increase in the burden of NRVHD due to population growth and aging and will continue to increase in the next 25 years. Our results can help shape a multifactorial approach and public policy to reduce the NRVHD burden throughout China.

Gender and socioeconomic disparities in global burden of chronic kidney disease due to glomerulonephritis: A global analysis.

To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability-adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age-standardized rate (ASR) of CKD due to glomerulonephritis. Paired t-test, paired Wilcoxon signed-rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age-standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low-middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p < .0001) and DALY rate (p < .0001) in men compared to women. The age-standardized DALY rate was negatively correlated with SDI (ρ=-0.64, p < .001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies.

The effect of a low versus high sodium diet on blood pressure in diabetic patients: A systematic review and meta-analysis of clinical trials.

There have been numerous clinical trials that have investigated the effect of sodium intake on blood pressure in diabetic patients. The purpose of this systematic review and meta-analysis was to evaluate the clinical trial studies performed on the effect of low sodium diet (LSD) versus high sodium diet (HSD) on blood pressure in diabetic patients. PubMed, Scopus, and Web of Science were systematically searched from database inception to July 10, 2021. Both type 1 and 2 diabetes was considered. Overall, there were 15 studies included in this meta-analysis. The weighted (WMD) mean difference with 95% confidence interval (CI) was calculated using a random-effects model. Risk of bias in the studies was assessed based on the Cochrane collaboration tool and the quality of all the studies was considered as good. Overall, LSD significantly reduced SBP (systolic blood pressure) (WMD: -3.79 mmHg, 95% CI: -6.02, -1.56) and DBP (diastolic blood pressure) (WMD: -1.62 mmHg, 95% CI: -2.84, -0.40), in comparison with HSD, in diabetics. However, LSD had no significant effect on MAP (mean arterial pressure) in comparison with HSD (WMD: -1.81, 95%CI: -5.49, 1.87). Although subgroup analysis could not attenuate heterogeneity in SBP, subgroup analysis in DBP based on duration (≤1week: WMD: -2.35, 95%CI: -3.69, -1.00, I 2 = 48.9%, p=0.081, >1week: WMD: -1.04, 95% CI: -2.83, 0.76, I 2 = 74.7%, p=0.003) and study design (cross-over: WMD: -1.94, 95% CI: -2.71, -1.17, I 2 = 32.1%, p=0.183, parallel: WMD: -2.17, 95% CI: -6.48, 2.13, I 2 = 82.4%, p=0.001) successfully detected sources of heterogeneity. LSD significantly reduced SBP and DBP, however, had no effect on MAP, in comparison with HSD.

The impact of a high-sodium diet regimen on cerebrovascular morphology and cerebral perfusion in Alzheimer's disease.

Various lifestyle factors such as chronic hypertension and a high-sodium diet regimen are shown to impact cerebrovascular morphology and structure. Unusual cerebrovascular morphological and structural changes may contribute to cerebral hypoperfusion in Alzheimer's disease (AD). The objective of this study was to examine whether a high-sodium diet mediates cerebrovascular morphology and cerebral perfusion alterations in AD. Double transgenic mice harboring Aβ precursor protein (APPswe) and presenilin-1 (PSEN1) along with wild-type controls were divided into four groups. Group A (APP/PS1) and B (controls) were both fed a high-sodium (4.00%), while group C (APP/PS1) and D (controls) were both fed alow-sodium (0.08% a regular chow diet) for three months. Then, changes in regional cerebral perfusion and diffusion, cerebrovascular morphology, and structure were quantified. A 3-month high-sodium diet causes pyknosis and deep staining in hippocampal neurons and reduced vascular density in both hippocampal and cortical areas (p <0.001) of APP/PS1. Despite vascular density changes, cerebral perfusion was not increased markedly (p=0.3) in this group, though it was increased more in wild-type controls (p=0.022). A high-sodium diet regimen causes cerebrovascular morphology alteration in APP/PS1 mouse model of AD.

S-50-5: SALT SENSITIVITY AS MARKER FOR HYPERTENSION MANAGEMENT

Arterial hypertension is one of the most critical risk factors for cardiovascular (CV) disease, stroke, and chronic kidney disease (CKD). According to the current guidelines on hypertension management, the identification of one or more CV risk factors requires an earlier and more intensive treatment paradigm. Salt sensitivity (SSy), defined as susceptibility to changes in blood pressure related to dietary salt intake, is a well-known independent risk factor for CV disease in both the general and hypertensive population, even though it is not included in current guidelines. Is has been reported that SSy affects 30_50% of hypertensive and 25% of normotensive subjects. Salt sensitivity is more common in the elderly, women, African Americans, and patients with CKD and insulin resistance. The diagnosis of SSy is complex and not entirely standardized. The two main methods for SSy assessment are the dietary protocol versus the acute salt load. The dietary protocols typically evaluate the blood pressure variation between short periods of low and high sodium diet and often differ in both the duration and the amount of salt intake. Acute test (which consists of an i.v. infusion of 2 L of physiological solution over 2 hours) evaluates mean blood pressure (MBP) variation between the end and the start of the infusion. Three different blood pressure responses are possible: no substantial variation [salt resistant (SR) subjects], an increase in blood pressure [salt sensitive (SS) subjects], or a paradoxical decrease in blood pressure [reverse salt sensitive (RSS) subjects]. Although RSS subjects have been recognized as a third distinct group since the early 1990 s, many studies included them in the group of SR subjects. Recently, the concept of reverse salt sensitivity has been re-evaluated in relation to CV risk. Previous studies have shown an increased risk of developing cardiovascular events, hypertensive heart disease and microalbuminuria among SS patients. In our recent paper, the SS and RSS condition appear to be equivalent risk factors for CV events in hypertensives. Finally, a J curve relationship between dietary salt and cardiovascular damage has been proposed. Different pathophysiological mechanisms can be involved in SSy: renal autoregulation (Pressure natriuresis curve), Renin angiotensin aldosterone system, sympathetic nervous system activity, Insulin resistance, peripheral vascular resistances, sodium storage skin, genetic predisposition. Classification according to salt sensitivity can help in personalization of salt intake indication, intensity of therapy and timing of follow up.

Macula Densa Nitric Oxide Synthase 1 Controls Renin Release and Renin-Dependent Blood Pressure Changes.

The function of macula densa nitric oxide synthase 1 (NOS1) in the regulation of renin release is controversial. This study was conducted to further elucidate the role of macula densa NOS1 in renin release and blood pressure regulation in response to salt challenges and hemorrhagic shock. To investigate the specific role of NOS1 in the macula densa within the kidney in response to varying sodium concentrations in the diet, tissue macula densa-specific NOS1 knockout (MD-NOS1KO) and wild type (WT) mice were subjected to sequential low (0.1% NaCl) and high (1.4% NaCl) sodium diets. Separate groups of mice, consisting of both MD-NOS1KO subgroup and WT subgroup, were induced hemorrhagic shock by retro-orbital bleeding of 12 mL blood/kg body weight. Mean arterial pressure (MAP) was measured by a radio-telemetry system. Plasma renin concentration (PRC) was measured with the radioimmunoassay for both sodium diet and hemorrhagic shock experiments. PRCs were 371 ± 95 and 411 ± 68 ng/mL/hr in WT and MD-NOS1KO mice fed a normal sodium diet, respectively. Low salt intake stimulated an increase in the renin release by about 260% in WT mice (PRC = 1364 ± 217 ng/mL/hr, p < 0.0001) compared to the PRC under normal salt diet. However, the stimulation was significantly blunted in MD-NOS1KO mice (PRC = 678 ± 104 ng/mL/hr, p < 0.001). High salt intake suppressed the PRC to about 61% of the PRC level under a normal salt diet (p < 0.0001). Deletion of macula densa NOS1 further inhibited renin release to 33% of the levels of a normal salt diet. Hemorrhagic shock induced about a 3-fold increase in PRC in WT mice, but only about a 54% increase in the MD-NOS1KO mice (p < 0.0001). The MAP values were substantially greater in WT mice than in MD-NOS1KO mice within the first 6 hours following hemorrhagic shock (p < 0.001). Thus, WT mice showed a much quicker recovery in MAP than MD-NOS1KO mice. Our study demonstrated that macula densa NOS1 plays an important role in mediating renin release. This mechanism is essential in maintaining blood pressure under hypovolemic situations such as hemorrhagic shock.

High sodium diet intake and cardiovascular diseases: An attributable death study in Tianjin, China.

There is clear evidence that high sodium intake is associated with many health issues including hypertension and cardiovascular diseases (CVDs). Several national and worldwide studies have estimated deaths from CVDs attributable to high sodium. But how to evaluate the impact of high sodium intake on diseases using regional routine monitoring and investigation data is necessary and important. Our study aimed to quantitatively evaluate the high sodium intake attributed to CVDs deaths based on the routine monitoring data from China National Nutrition and Health Survey (CNNHS) in Tianjin, China. The population attributable fractions (PAF) were calculated by comparing the observed systolic blood pressure (SBP) distribution with the theoretical minimum or counterfactual distribution by sex and age groups. The results showed that CVDs deaths due to elevated SBP were 22728 (95% uncertainty intervals: 22679-23050), accounting for 62.8% of total CVDs deaths. According to sodium intake recommended by World Health Organization (WHO), PAF of CVDs deaths attributable to high sodium diet in our study was 14.6% of total CVDs deaths, accounting for 5228 (95% UI: 5005-5998) cases. The dietary sodium intake of residents is nearly three times than sodium intake recommended by WHO. If sodium intake was reduced to reference level, the potential avoidable CVD deaths attributable to the SBP-raising effect were more than 5200 among adults 25 aged and over in Tianjin. This evaluation method can be extended to other cities.

Intensifying self-awareness of undergraduate students toward hypertension risk factors through health education

Introduction: Hypertension in adolescents’ risk factors include foods that contain high sodium, lack of physical activity, stress, obesity, alcohol consumption, and smoking. Order to prevent hypertension incidence in adolescents by increasing self-awareness through the provision of health education. This study aimed to determine the health education effect regarding the risk factors of hypertension (stress and sodium diet) on the self-awareness of undergraduate students in Yogyakarta. Methods: This study was a quantitative study with a quasi-experiment pretest &amp; posttest with a control group design. The hypertension self-awareness questionnaire was used in this study and the results will be classified into two groups (the control and the intervention group). The sample obtained in this study was 54 respondents. The Mann-Whitney U and Wilcoxon Signed Rank test was done in this study. Results: It showed that there were significant differences in the intervention group and control group. There were significant differences in results found before and after health education (significance value 0.000), while the result for the control group is 0.06, which indicates that there were no significant differences before and after the leaflet. Conclusions: It can be concluded that health education regarding risk factors for hypertension (stress and a high sodium diet) can increase self-awareness for undergraduate students in Yogyakarta.

Sodium and Potassium Urinary Excretion Among Malaysian Adults Claiming to Practice Salt-control: Findings from the Malaysian Community Salt Survey (MyCoSS)

Introduction: Raised blood pressure is associated with diet high in sodium and low in potassium. According to the Malaysian Community Salt Survey (MyCoSS), Malaysian adults consume a high sodium diet, despite half claiming that they control their salt intake. The objective of this study was to investigate the association of sodium and potassium with salt-control claims among adults from the MyCoSS study based on 24-h urinary excretion. Methods: Data of 1,047 respondents aged 18 years and above who completed the knowledge, attitude, and practice (KAP) questionnaire were used in this study. Face-to-face interviews were conducted to acquire information on sociodemographic, medical reports and KAP on salt intake. Sodium and potassium level were assessed from 24-hr urine specimen, anthropometric measurements were done using WHO criteria, while blood pressure was measured using validated digital blood pressure monitor. Descriptive and analysis of variance (ANOVA) were used to determine the associations between urinary sodium and potassium with salt-control claims and practices. Results: The consumption of sodium was higher than recommended, while potassium was lower among respondents who claimed to control their salt intake. Significant associations were found between sodium intake with marital status, ethnicity, education level and employment status. Meanwhile, significant associations were found between potassium intake with ethnicity and employment status. Conclusion: Sodium intake was high, and potassium intake was low among respondents who claimed they control their salt intake. Further study with detailed intervention on specific target group is required to improve sodium and potassium intakes among Malaysian adults.

Inverse Salt Sensitivity of Blood Pressure Is Associated with an Increased Renin-Angiotensin System Activity.

High and low sodium diets are associated with increased blood pressure and cardiovascular morbidity and mortality. The paradoxical response of elevated BP in low salt diets, aka inverse salt sensitivity (ISS), is an understudied vulnerable 11% of the adult population with yet undiscovered etiology. A linear relationship between the number of single nucleotide polymorphisms (SNPs) in the dopamine D2 receptor (DRD2, rs6276 and 6277), and the sodium myo-inositol cotransporter 2 (SLC5A11, rs11074656), as well as decreased expression of these two genes in urine-derived renal proximal tubule cells (uRPTCs) isolated from clinical study participants suggest involvement of these cells in ISS. Insight into this newly discovered paradoxical response to sodium is found by incubating cells in low sodium (LS) conditions that unveil cell physiologic differences that are then reversed by mir-485-5p miRNA blocker transfection and bypassing the genetic defect by DRD2 re-expression. The renin-angiotensin system (RAS) is an important counter-regulatory mechanism to prevent hyponatremia under LS conditions. Oversensitive RAS under LS conditions could partially explain the increased mortality in ISS. Angiotensin-II (AngII, 10 nmol/L) increased sodium transport in uRPTCs to a greater extent in individuals with ISS than SR. Downstream signaling of AngII is verified by identifying lowered expression of nuclear factor erythroid 2-related factor 2 (NRF2), CCCTC-binding factor (CTCF), and manganese-dependent mitochondrial superoxide dismutase (SOD2) only in ISS-derived uRPTCs and not SR-derived uRPTCs when incubated in LS conditions. We conclude that DRD2 and SLC5A11 variants in ISS may cause an increased low sodium sensitivity to AngII and renal sodium reabsorption which can contribute to inverse salt-sensitive hypertension.

Disease burden and risk factors of ischemic heart disease in China during 1990-2019 based on the Global Burden of Disease 2019 report: A systematic analysis.

The aim of this study was to identify the disease burden and risk factors of ischemic heart disease (IHD) in China, during 1990-2019, through a systematic analysis using the Global Burden of Disease (GBD) 2019 report in order to provide first-hand information for primary and secondary prevention of IHD in China. Data on the rates of incidence, death, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of IHD were obtained from GBD2019 to determine the disease burden and risk factors of IHD in China. The rates of incidence, death, YLLs, YLDs, and DALYs of IHD in China increased at different levels during 1990-2019. The annual rate of change in incidence, death, YLLs, YLDs, and DALYs of IHD were 1.31%, 1.57%, 0.93%, 1.14%, and 0.94%, respectively. In 2019, the YLDs of IHD in Chinese women were higher, while the rates of incidence and death, YLLs, and DALYs were lower in Chinese women than in Chinese men. The disease burden of IHD had significant age differences, and people aged ≥70 years had the highest disease burden. A total of 24 risk factors were associated with the rates of death and DALYs of IHD, and the five most significant risk factors were high systolic blood pressure, high LDL cholesterol (LDL-C), smoking, ambient particulate matter pollution, and intake of a high-sodium diet. From 1990 to 2019, a high annual rate of change in IHD-related deaths and DALYs was observed due to ambient particulate matter pollution, high body mass index (BMI), and intake of a diet high in processed meat. The results of the study revealed that the disease burden of IHD in China was on the rise, especially in people aged ≥70 years. The main disease burden of IHD in male patients was premature death and that in female patients was disability. Environmental, behavioral, and metabolic factors were considered the three main risks of the disease burden of IHD, with metabolic factors having the greatest impact. Therefore, periodic health check-ups and high-risk factor interventions for key populations should be strengthened from the grassroots level, which are conducive to further reducing the disease burden of IHD in China.

RF33 | PSAT79 Chronic Activation of Gq-Signaling in the Mouse Adrenal Cortex Disrupts Zonation and Causes Aldosterone Production in the Zona Fasciculata

Abstract Background The mammalian adrenal cortex is composed of the zona glomerulosa (ZG), zona fasciculata (ZF), and in some species the zona reticularis (ZR). Each layer is characterized by a specific steroidogenic enzyme expression pattern that leads to selective production of mineralocorticoids, glucocorticoids or adrenal androgens. ZG-specific expression of cytochrome P450 aldosterone synthase (Cyp11b2) and aldosterone biosynthesis are renin-angiotensin-dependent processes in which the Gq-signaling pathway is activated by angiotensin II (AngII). Gq-signaling can be exogenously activated using Gq-coupled designer receptors exclusively activated by designer drug (GqDREADD) technology. Using transgenic mice with targeted expression of GqDREADD to the adrenal cortex, we previously demonstrated that short-term receptor activation increased adrenal Cyp11b2 and aldosterone production. Herein, we hypothesized that prolonged activation of mouse adrenal cortex Gq-signaling would exacerbate the aldosterone levels and promote the transdifferentiation of ZF cells to ZG cells. Methods Transgenic AS+/Cre hM3Dq (GqDREADD) female mice were engineered through crossing GqDREADD mice with Cyp11b2-regulated Cre recombinase mice. Mice were placed on a high sodium diet (to suppress physiologic renin) and orally provided the GqDREADD ligand, clozapine N-oxide (CNO; n=10) or control (n=8) for 6 weeks followed by collection of blood and adrenals. Mineralocorticoid levels were quantified using LC-MS/MS. Adrenal RNA was isolated and assessed by RNAseq for transcriptomic changes, and RT-qPCR analysis for ZG- and ZF-specific transcript markers, Cyp11b2 and Cyp11b1 (marker of ZF), respectively. Transcripts for β-catenin (Ctnnb1) and axin-2 (Axin2) (markers of the WNT signaling pathway) were also analyzed. Immunofluorescence (IF) studies examined adrenal expression of Cyp11b1 and Cyp11b2 in mice treated for 1 month. Results CNO treatment caused plasma aldosterone to increase 613-fold from 7.9 ±2.5 pg/mL to 4810.7 ±1110.7 pg/mL (p&amp;lt;0.01). Levels of 18-hydroxycorticosterone increased 70-fold from 144.9 ±22.0 to 10143.2 ±1479.6 pg/mL (p&amp;lt;0.0001). Corticosterone levels were unaffected. RT-qPCR analysis showed adrenal Cyp11b2 transcripts to be 224-fold higher (p&amp;lt;0.0001) in the CNO-treated group while a 30% decrease in Cyp11b1 levels was observed (p&amp;lt;0.01) compared to the controls. IF demonstrated hybrid ZF cells aberrantly expressing both Cyp11b2 and Cyp11b1. Within the normal mouse adrenal, the outer ZG exhibits high WNT/β-catenin (Ctnnb1) activation. To determine if chronic CNO treatment impacted overall adrenal WNT signaling, Ctnnb1 and Axin2 (a downstream β-catenin gene target) were examined. Analysis revealed no statistical difference in Ctnnb1 and Axin2 transcript levels in treated mice. RNAseq revealed that 242 transcripts were increased in adrenals from treated mice, while 109 decreased (&amp;gt;3-fold change; p&amp;lt;0.01). Induced transcripts include Cyp11b2 and its transcriptional regulators, Nr4a1 and Nr4a2. Conclusion Overall, these findings demonstrate that chronic Gq-signaling is sufficient to cause ZF cells to produce aldosterone and express Cyp11b2. The findings also suggest that the adrenocortical WNT signaling pathway is not increased by the activation of Gq-signaling. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:36 p.m. - 12:41 p.m.

Sodium in processed meats produced by local butcheries in Tshwane, South Africa

The common use of sodium in different compositions, is as a preservative, for colouring, curing, flavouring and as a binding agent in processed meats, it is also used for improved shelf life and distinct palatability. Even with modern food processing methods, sodium is still essential in manufacturing of meat derivatives. Continuous consumption of high sodium diets is associated with adverse chronic health effects, such as cardiovascular diseases, hypertension, stroke, cancers, among others, which have been on the rise. As a result, there has been a global drive by organisations such as the World Health Organization (WHO) to advise member states to reduce dietary sodium levels in various foods, including processed meats. Consequently, South Africa promulgated the first sodium reduction regulations in Africa by 2013, intended to reduce sodium in certain foodstuffs, including processed meat products. The objectives of this study were to determine (1) the level of sodium in processed meats produced by local butcheries in the City of Tshwane (CoT), Gauteng, South Africa and (2) to compare the amount of sodium in processed meats, determined using the two South African legislated methods, namely Flame Atomic Absorption Spectroscopy (FAAS) and Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES). A cross-sectional approach with qualitative and experimental dimensions approach was followed. Processed meat production records obtained from randomly selected butcheries in CoT (122) revealed that the top six commonly produced processed meats were boerewors (90.2 %), braaiwors (87.7 %), biltong (86.9 %), drywors (62.3 %), viennas (45.9 %) and burger patties (43.5 %). Subsequently, sampling (n=396) of the top six products from 66 randomly selected butcheries was done. The findings of the study revealed that processed meats analysed using ICP-AES and FAAS contained mean sodium levels of 1449 mg/100 g and 649 mg/100 g, respectively (p&lt;0.0001), which were higher than the South African legal sodium limits. The concentration of sodium of products determined using ICP-AES (64.7 - 9201 mg/100 g) was significantly (p&lt;0.0001) higher than in the same products analysed using FAAS (35.4 - 2351 mg/100 g). From the findings of this study, sodium reduction requires a concerted effort in enforcing the South African mandatory sodium limits in local butcheries in processed meats. The results of legislated sodium test methods must be comparable to ensure equal level of compliance. Key words: meat products, sodium reduction, processed food, processed meat, sodium limits

(Digital Presentation) Point-of-Care Diagnostic Device for Na/K Urinalysis

The Centers for Disease Control and Prevention (CDC) reports 47% of adults in the United States have hypertension [1]. Dietary risks constitute the largest disease risk factor in the US [2], whereby the largest single contributor to that risk is high dietary sodium intake [3].The World Health Organization (WHO) recommends that individuals reduce sodium (Na) and increase potassium (K) intake to lower blood pressure and improve cardiovascular health [4,5]. Emerging research has shown that urinary Na/K ratio is more strongly related to blood pressure, cardiovascular disease, and stroke than Na and K considered separately [6]. Urine Na guided dietary guidance enhances the ability to monitor sodium reduction and blood pressure [7]. Manual collection for chronic urine testing is too burdensome a process for practical everyday use. We have developed an accurate biosensor capable of being easily integrated into users’ daily routine for real-time and fully automated longitudinal Na/K analysis.Reference[1] Centers for Disease Control and Prevention, (2021),https://www.cdc.gov/bloodpressure/facts.htm#:~:text=Nearly%20half%20of%20adults%20in,are%20taking%20medication%20for%20hypertension.[2] The US Burden of Disease Collaborators; A.H., Mokdad, JAMA, 319(14),1444-1472 (2018).[3] GBD 2017 Diet Collaborators, The Lancet, 393(10184), 1958-1972 (2019).[4] WHO Guideline Sodium intake for adults and children. Geneva: World Health Organization (WHO); 2012.[5] WHO Guideline Potassium intake for adults and children. Geneva: World Health Organization (WHO); 2012.[6] T. Iwahori; K. Miura; H. Ueshima; S. Tanaka-Mizuno; Q. Chan; H. Arima; A. R. Dyer; P. Elliott; J. Stamler, Hypertens Res, 42(10), 1590-1598 (2019).[7] T. Takada; M. Imamoto; S. Sasaki; T. Azuma; J. Miyashita; M. Hayashi; S. Fukuma; S. Fukuhara, Hypertens Res, 41(7), 524-530 (2018).Figure 1 (A) Urinalysis system installed in a urinal that can catch a stream of urine in real-time. (B) Biosensor cyclic voltammetry curve of human urine. Figure 1