High Dietary Sodium Intake Research Articles

Association between intake of sodium, potassium, sodium-to-potassium ratio, and blood pressure among US adults.

High dietary sodium and low potassium intake is associated with high blood pressure (BP). The current study aimed to determine if the sodium-to-potassium ratio is more strongly associated with low (130-139/80-89 mm Hg) and high (≥140/90 mm Hg) BP thresholds among US adults than either sodium or potassium alone. A total of 30,776 patients aged ≥20 years with complete blood pressure participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Demographic information and health characteristics were compared between men and women using the chi-square test for categorical variables and independent samples t-test for continuous variables. Logistic regression was performed to investigate the association of the odds ratios (OR) of different levels of sodium, potassium, and sodium-to-potassium ratio. After multivariable adjustment (age, gender, Body mass index, Smoking, education, Race, Alcohol, total energy intake, and physical activity), no relationship has been observed between high versus low sodium-to-potassium ratio and BP threshold of 130-139/80-89 mm Hg (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.92-1.12). Higher sodium-to-potassium ratio (OR=1.24; CI: 1.11-1.38) and dietary intake of potassium (OR=0.66; CI: 0.55-0.80) showed significant association in reducing the BP threshold of ≥140/90 mm Hg. In dose-response analysis, higher BP ≥140/90 mm Hg was inversely associated with higher potassium intake. Furthermore, the sodium-to-potassium ratio showed higher odds in predicting the BP of patients aged ≤60 years, underweight, nonsmokers, and non-alcohol users. The study confirms an inverse association between higher potassium intake and higher BP threshold. The Doses-response analyses showed sodium-to-potassium ratio is a better predictor of BP thresholds than sodium or potassium alone.

The role of body mass index in the association between dietary sodium intake and blood pressure: A mediation analysis with NHANES

Background and aimsRecent research demonstrated that obesity and high dietary sodium intake, the two established risk factors for hypertension, were associated with each other. The objective was to investigate the potential indirect effect of sodium intake on blood pressure via body mass index (BMI). Methods and resultsUsing ten years data from US NHANES (2007–2016), the study included adult participants (>20 years old) who were not taking antihypertensive medications and without baseline diseases (n = 12,262). BMI was modelled as the mediator of sodium intake on systolic and diastolic blood pressure, adjusted for age, sex, socioeconomic status, smoking, drinking, physical activity, calorie intake, fluid intake and potassium intake. Mediation analysis was performed to evaluate total effect, direct effect and indirect effect via BMI. Subgroup analyses based on three age subgroups (20–40, 41–60 and ≥61 years old) were performed. The mean age was 39.29 (13.4) years and 53.1 (0.45) % were males. The mean BMI was 27.8 (6.20) kg/m2. Overall, 1 g/d increase in sodium intake was associated with an increased systolic blood pressure by 0.36 (95% confidence interval 0.14 to 0.58) mmHg, with a direct effect (0.14 (0.09–0.19)) and an indirect effect via BMI (0.23 (0.02–0.44)). The indirect effect was mainly observed in participants ≤60 years old. ConclusionSodium intake showed both direct effect and indirect effect (via BMI) on systolic blood pressure in US NHANES. The findings provide evidence for combining sodium restriction and weight reduction measures for prevention of hypertension. Cautions should be taken when generalizing the findings to other populations with lower average BMI.

Abstract P216: Cholinergic-mediated Salt-Sensitive Hypertension In A Genetic Model Of Essential Hypertension

Inflammation plays a key role in the pathogenesis of hypertension. High dietary sodium intake has been associated with inflammation in patients suffering from high blood pressure & atherosclerosis. Our lab has shown that development of hypertension in a genetic model of human essential hypertension, the Spontaneously Hypertensive Rat (SHR), is dependent on nicotinic acetylcholine receptor (nAChR) mediated renal inflammation, which leads to enhanced expression of the renal sodium-potassium chloride cotransporter (NKCC2). Based on these findings we hypothesized that sodium sensitivity may play a role in the development of cholinergic hypertension. To investigate this hypothesis, we infused young pre-hypertensive SHR and Wistar Kyoto (WKY, normotensive control) rats with either saline or nicotine (15mg/kg/day) and placed them on either low-salt (LSD, 0.01% NaCl) or high-salt (HSD, 4% NaCl) diet for 2 wks. There was no change in systolic blood pressure (SBP) in saline or nicotine infused WKY with either LSD or HSD. Similarly, there was no difference between the SBP of saline infused SHR with either LSD or HSD. Interestingly, nicotine infusion did not change SBP in LSD fed SHR, but did result in ~20% increase in SBP in HSD fed SHR (122.0 ± 0.7 vs. 146.2 ± 0.2mmHg, p= 0.01). HSD alone induced a 2.25-fold increase in renal NKCC2 expression compared to LSD in saline infused SHR (p=0.006). In comparison to saline, nicotine infusion further induced a 58% increase in renal NKCC2 expression in SHR fed HSD (p=0.004). Renal NKCC2 expression did not change in WKY with either diet or nicotine infusion. Nicotine infused SHR on a HSD also manifested a 16% sodium retention compared to saline infused SHR (2.1 ± 0.1 mM/gBW vs. 2.5 ± 0.1 mM/gBW, p = 0.017). Nicotine infused SHR had 1.7 times more renal IL-6 than saline-infused SHR (1442. ± 212 vs 826 ± 103 pg/25mg total protein, p=0.04) and 9 times more renal IL-6 than nicotine-infused WKY controls (1442. ± 212 vs 148. ± 71 pg/25mg total protein, p=0.0041) under HSD conditions. Taken together with our previously published data, we conclude that NKCC2 likely plays a role in cholinergic-mediated renal inflammation and hypertension.

Sodium Toxicity in the Nutritional Epidemiology and Nutritional Immunology of COVID-19.

Dietary factors in the etiology of COVID-19 are understudied. High dietary sodium intake leading to sodium toxicity is associated with comorbid conditions of COVID-19 such as hypertension, kidney disease, stroke, pneumonia, obesity, diabetes, hepatic disease, cardiac arrhythmias, thrombosis, migraine, tinnitus, Bell’s palsy, multiple sclerosis, systemic sclerosis, and polycystic ovary syndrome. This article synthesizes evidence from epidemiology, pathophysiology, immunology, and virology literature linking sodium toxicological mechanisms to COVID-19 and SARS-CoV-2 infection. Sodium toxicity is a modifiable disease determinant that impairs the mucociliary clearance of virion aggregates in nasal sinuses of the mucosal immune system, which may lead to SARS-CoV-2 infection and viral sepsis. In addition, sodium toxicity causes pulmonary edema associated with severe acute respiratory syndrome, as well as inflammatory immune responses and other symptoms of COVID-19 such as fever and nasal sinus congestion. Consequently, sodium toxicity potentially mediates the association of COVID-19 pathophysiology with SARS-CoV-2 infection. Sodium dietary intake also increases in the winter, when sodium losses through sweating are reduced, correlating with influenza-like illness outbreaks. Increased SARS-CoV-2 infections in lower socioeconomic classes and among people in government institutions are linked to the consumption of foods highly processed with sodium. Interventions to reduce COVID-19 morbidity and mortality through reduced-sodium diets should be explored further.

Is socio-demographic status, body mass index, and consumption of food away from home associated with high sodium intake among adults in Malaysia?: findings from the Malaysian Community Salt Survey (MyCoSS)

BackgroundStudies have shown that having away from home meals contributes to high sodium intake among young people and those who lived in urban areas. This study aimed to determine the association between dietary sodium intake, body mass index, and away from home meal consumption behaviour among Malaysian adults.MethodsMyCoSS was a cross-sectional household survey involving 1440 adults age 18 years and above. This study utilized stratified cluster sampling to obtain a nationally representative sample. Data was collected between October 2017 and March 2018. Socio-demographic information, dietary assessment using food frequency questionnaire (FFQ), and away from home meal consumption were assessed through a face-to-face interview by trained health personnel. Descriptive analysis and logistic regression were applied to identify the association of socioeconomic status and away from home meal consumption with dietary sodium intake.ResultsA total of 1032 participants completed the FFQ, with a mean age of 48.8 + 15.6 years. Based on the FFQ, slightly over half of the participants (52.1%) had high sodium intake. Results showed that 43.6% of participants consumed at least one to two away from home meals per day, while 20.8% of them had their three main meals away from home. Participants aged less than 30 years old were the strongest predictor to consume more sodium (adjusted OR: 3.83; 95%CI: 2.23, 6.58) while those of Indian ethnicity had significantly lower sodium intake. Surprisingly, having three away from home meals per day was not associated with high dietary sodium intake, although a significant association (crude OR; 1.67, 95% CI: 1.19, 2.35) was found in the simple logistic regression. Obese participants were less likely to have high dietary sodium intake compared with the normal BMI participants in the final model.ConclusionOver half of the participants consumed sodium more than the recommended daily intake, especially those who consumed three away from home meals. However, there was no significant association between high sodium intake and having three away from home meals per day. The promotion of healthy cooking methods among the public must continue to be emphasized to reduce the dietary sodium intake among Malaysian adults.

Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome

BackgroundHigh sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available. ObjectivesThis study tested whether a high sodium (HS) diet reduces orthostatic tachycardia (Δ heart rate) and upright heart rate compared with a low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine. MethodsA total of 14 POTS patients and 13 healthy control subjects (HC), age 23 to 49 years, were enrolled in a crossover study with 6 days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. Supine and standing heart rate, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine were measured. ResultsIn POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in HC on the HS diet (median 117 beats/min [interquartile range: 98 to 121 beats/min], 46 beats/min [interquartile range: 32 to 55 beats/min], and 753 pg/ml [interquartile range: 498 to 919 pg/ml] in POTS vs. 85 beats/min [interquartile range: 77 to 95 beats/min], 19 beats/min [interquartile range: 11 to 32 beats/min], and 387 pg/ml [interquartile range: 312 to 433 pg/ml] in HC, respectively), despite no difference in the measured PV. ConclusionsIn POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases Δ heart rate. (Dietary Salt in Postural Tachycardia Syndrome; NCT01547117)

Blood Pressure in Childhood and Adolescence.

Elevated blood pressure (BP) and hypertension commonly occur in children and adolescents and increase the risk of cardiovascular disease in adulthood. The purpose of this review is to summarize recent research in pediatric hypertension including changes in defining hypertension, BP measurement techniques, hypertension epidemiology, risk factors, treatment, and BP-related target organ damage. Defining pediatric hypertension using the 2017 American Academy of Pediatrics' updated Clinical Practice Guideline resulted in a larger proportion of children being classified as having elevated BP or hypertension compared with prior guidelines. Trends in the distribution of BP among US children and adolescents suggest that BP levels and the prevalence of hypertension may have increased from 2011-2014 to 2015-2018. Factors including a family history of hypertension, obesity, minority race/ethnicity, physical inactivity, high dietary intake of sodium, and poor sleep quality are associated with an increased prevalence of elevated BP and hypertension. Evidence of a linear relationship between systolic BP and target organ damage indicates that BP levels currently considered normal could increase the risk of target organ damage in childhood. Lifestyle changes, such as adhering to the Dietary Approaches to Stop Hypertension diet, are a central component of effectively reducing BP and have been shown to reduce target organ damage. Pharmacologic treatment using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is an effective and safe method for reducing BP among children with uncontrolled BP after implementing lifestyle changes. Research gaps in the prevention, detection, classification, and treatment of hypertension in children demonstrate opportunities for future study.

SODIUM INTAKE, LIFE EXPECTANCY AND ALL-CAUSE MORTALITY

Objective: Since dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, a high dietary sodium intake can be expected to curtail life span. We tested this hypothesis by analyzing the relationship between sodium intake and life expectancy as well as survival in 181 countries worldwide. Design and method: We correlated age-standardized estimates of country specific average sodium consumption with healthy life expectancy at birth and at age of 60 years, and all-cause mortality for the year of 2010, after adjusting for potential confounders such as gross domestic product per capita and body mass index. We considered global health estimates as provided by World Health Organization. Results: Among the 181 countries included in this analysis, we found a positive correlation between sodium intake and healthy life expectancy at birth (R2 = 0.661, p < 0.001), as well as healthy life expectancy at age 60 (R2 = 0.600, p = 0.048). Conversely, all-cause mortality correlated inversely with sodium intake (R2 = 0.597, p < 0.001), Figure 1. In a sensitivity analysis restricted to 46 countries in the highest income class, sodium intake continued to correlate positively with healthy life expectancy at birth (R2 = 0.533, p < 0.001) and inversely with all-cause mortality (R2 = 0.497, p < 0.001). Figure 1: Relation of sodium intake (grams/day) for the year of 2010 and healthy life expectancy at birth (in years) and age-standardized death rates (ASDR) for all-cause mortality in 181 countries worldwide. Schematic pattern of change in life expectancy and all-cause mortality with sodium intake in 181 countries worldwide. Note that proposed upper limits by some organizations such as AHA, WHO and ESC are associated with rather low life expectancy and high mortality. Conclusions: Our observation of sodium intake correlating positively with life expectancy and inversely with all-cause mortality worldwide and in high income countries argues against dietary sodium intake being a culprit of curtailing life span or a risk factor for premature death. These data are observational and should not be used as a base for nutritional interventions.

GENETICALLY, DIETARY SODIUM INTAKE IS CAUSALLY ASSOCIATED WITH SALT-SENSITIVE HYPERTENSION RISK IN A COMMUNITY-BASED COHORT STUDY: A MENDELIAN RANDOMIZATION APPROACH

Objective: Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR). Design and method: We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1,282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Results: Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR = 0.356, 95% CI = 0.236–0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR = 2.114, 95% CI = 2.004–2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1 mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype. Conclusions: Our findings suggest that dietary sodium intake may be causally associated with hypertension risk.

DISTRIBUTION OF SPOT URINARY ELECTROLYTES AND THEIR PREDICTED 24 HOUR LEVELS BY ETHNICITY ASSOCIATIONS WITH MORTALITY IN A LONGITUDNAL COHORT

Objective: Hypertension is a modifiable risk factor for development of cardiovascular disease. Increased urinary sodium excretion, representing high dietary sodium intake is associated with hypertension. Observational cohort studies consistently demonstrate a low sodium intake is also associated with increased mortality. It is not known what the optimal amount of salt intake is good for cardiovascular health. Hypertension is a modifiable risk factor for development of cardiovascular disease. Increased urinary sodium excretion, representing high dietary sodium intake is associated with hypertension. Observational cohort studies consistently demonstrate a low sodium intake is also associated with increased mortality. It is not known what the optimal amount of salt intake is good for cardiovascular health. Design and method: Urine samples were obtained from 331 people [100 Afro-Caribbean (AC), 118 European and 113 Gujarati Indians] to estimate 24-hour sodium and potassium excretion. Association between estimated urinary sodium, potassium and creatinine excretion to composite outcome of major cardiovascular event and death were examined. We also aimed to study if ethnicity influenced this relationship. Results: We noted heterogeneity in association between sodium, potassium, creatinine excretion and mortality. Significantly higher, age-sex adjusted, spot urinary sodium (OR- 2.7; CI – 1.9–3.2) and creatinine (OR- 1.7; CI – 1.2–2.2) levels were seen in AC men who also had higher mean diastolic blood pressure (84 ± 5.5 vs 78 ± 3.3; p < 0.05). Overall, 42.9% (n = 142) of the cohort were hypertensive. Of the 331 eligible participants at baseline, a total 69 cardiovascular deaths were recorded. Spot sodium levels were higher in those who died from cardiovascular causes [(125.3; CI- 116.9, 133.7) mmol/l] vs [(108.7; CI - 99.4 – 118.0); p = 0.02]. Survival was associated with a urinary sodium below and urinary potassium above the median. There was no survival advantage associated with differences in creatinine output. Conclusions: This study estimates a sodium intake of between 2.0 g/day and 2.5 g/day as being associated with a lower risk of death and cardiovascular events. A higher potassium excretion was associated with a lower risk of death and cardiovascular events. Creatinine output made no difference to survival advantage.

Altered Taste Perception for Sodium Chloride in Patients With Primary Aldosteronism: A Prospective Cohort Study.

[Figure: see text].

Paradoxical Increase of 24-Hour Urinary Aldosterone Levels in Obese Patients With Resistant Hypertension on a High Salt Diet

Having previously reported that aldosterone levels increase progressively with body mass index (BMI), the current analysis was done to determine to what extent this association is related to dietary high salt intake. We anticipated that aldosterone levels would decrease with higher sodium status consistent with classical suppression of aldosterone release secondary to progressive fluid retention induced by high dietary sodium intake. Cross-sectional analysis of a large diverse cohort of 2,705 patients with resistant hypertension (HTN) seen in a referral HTN Clinic. Dietary sodium intake was indexed by 24-hour (h) urinary sodium (UNa), aldosterone status was determined by plasma aldosterone concentration, plasma renin activity, and 24 h urinary aldosterone (UAldo). Patients with normal weight served as control. In this study, 1,572 individuals with complete 24 h urine collections were analyzed. Mean BMI was 32.5 ± 7.1 kg/m2 and ranged from 24.6 ± 2.4 kg/m2 (first quartile) to 41.0 ± 4.2 kg/m2 (fourth quartile). BMI was positively associated with 24 h UNa and UAldo levels (P < 0.0001), 24 h UNa and UAldo. There was a positively stronger correlation in obese (r = 0.273, P < 0.0001) compared with normal weight individuals (r = 0.108, P = 0.0342) independent of number and classes of antihypertensive medications. Our analysis shows that there is an altered regulation of aldosterone in obese patients in the setting of high dietary salt intake.

Assessment of Dietary Sodium Intake Using the Scored Salt Questionnaire in Autosomal Dominant Polycystic Kidney Disease.

The excess intake of dietary sodium is a key modifiable factor for reducing disease progression in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that the scored salt questionnaire (SSQ; a frequency questionnaire of nine sodium-rich food types) is a valid instrument to identify high dietary salt intake in ADPKD. The performance of the SSQ was evaluated in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 during the screening visit of the PREVENT-ADPKD trial. High dietary sodium intake (HSI) was defined by a mean 24-h urinary sodium excretion ≥ 100 mmol/day from two collections. The median 24-h urine sodium excretion was 132 mmol/day (IQR: 112–172 mmol/d) (n = 75; mean age: 44.6 ± 11.5 years old; 53% female), and HSI (86.7% of total) was associated with male gender and higher BMI and systolic blood pressure (p < 0.05). The SSQ score (73 ± 23; mean ± SD) was weakly correlated with log10 24-h urine sodium excretion (r = 0.29, p = 0.01). Receiving operating characteristic analysis showed that the optimal cut-off point in predicting HSI was an SSQ score of 74 (area under the curve 0.79; sensitivity 61.5%; specificity 90.0%; p < 0.01). The evaluation of the SSQ in participants with a BMI ≥ 25 (n = 46) improved the sensitivity (100%) and the specificity (100%). Consumers with an SSQ score ≥ 74 (n = 41) had higher relative percentage intake of processed meats/seafood and flavourings added to cooking (p < 0.05). In conclusion, the SSQ is a valid tool for identifying high dietary salt intake in ADPKD but its value proposition (over 24-h urinary sodium measurement) is that it may provide consumers and their healthcare providers with insight into the potential origin of sodium-rich food sources.

Genetically, dietary sodium intake is causally associated with salt-sensitive hypertension risk in a community-based cohort study: a Mendelian randomization approach

Abstract Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR). We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1,282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR = 0.356, 95% CI = 0.236–0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR = 2.114, 95% CI = 2.004–2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1 mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype. Our findings suggest that dietary sodium intake may be causally associated with hypertension risk. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1D1A3B03034119, 2014M3C9A3064552), and the KRIBB Initiative program. This research was also supported by the Medical Research Center Program (2017R1A5A2015369). This work was supported (in part) by the Yonsei University Research Fund 2017. Bioresources for this study were provided by the National Biobank of Korea and the Centers for Disease Control and Prevention, Republic of Korea (2017-009).

Maternal Intake of Flaxseed During Lactation and Exercise Training Protect Against Salt Overload-Induced Aortic Remodeling in Adult Offspring

Abstract Background High dietary sodium intake can induce endothelial stiffness even without changes in blood pressure. Objectives To evaluate the effects of exercise training and chronic intake of sodium chloride solution on aortic morphology of male offspring of rat dams who consumed flaxseed during lactation. Methods Female rats were fed with a control diet or a flaxseed diet during lactation. At weaning, two male offspring of each rat dam were allocated into eight groups for 180 days: four groups received [...]

Ambulatory blood pressure in relation to interaction between dietary sodium intake and serum uric acid in the young

Purpose We hypothesise that dietary sodium intake interacts with serum uric acid to influence blood pressure (BP) in children and adolescents. In the present study, we investigated ambulatory BP in relation to hyperuricaemia, dietary sodium intake and their interaction in children and adolescents with hypertension. Materials and methods A total of 616 study participants were 10–24 years old and had primary hypertension diagnosed after admission in a specialised inpatient ward. Ambulatory BP monitoring was performed during hospitalisation. 24-h urine was collected for measurements of electrolytes. Hyperuricaemia was defined as a serum uric acid of ≥327.25 μmol/L in patients <18 years old and of ≥420 and ≥360 μmol/L, respectively, in male and female patients ≥18 years old. Results In adjusted analyses, patients with hyperuricaemia (n = 283), compared with those with normal serum uric acid, had similar 24-h systolic BP (131.7 mmHg, p = 0.54) and a significantly (p ≤ 0.005) lower 24-h diastolic BP (77.5 vs. 80.9 mmHg) and higher 24-h pulse pressure (54.2 vs. 51.7 mmHg). In similar adjusted analyses, 24-h ambulatory pulse pressure, but not systolic/diastolic BP (p ≥ 0.12), significantly differed across the quartile distributions of urinary sodium excretion (p for trend ≤ 0.04). Further adjusted analyses showed significant (p ≤ 0.04) interaction between serum uric acid and urinary sodium excretion in relation to 24-h systolic BP. In patients with hyperuricaemia (p = 0.04), but not those with normal serum uric acid (p = 0.13), 24-h systolic BP was significantly associated with urinary sodium excretion, with a 6.5 ± 2.1 mmHg difference between quartiles 4 and 1. Similar results were observed for daytime and night-time BP and pulse pressure. Conclusions Both hyperuricaemia and higher dietary sodium intake were associated with higher pulse pressure, and their interaction further heightened systolic BP.

Genetically, Dietary Sodium Intake Is Causally Associated with Salt-Sensitive Hypertension Risk in a Community-Based Cohort Study: a Mendelian Randomization Approach.

Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR). We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR, 0.356; 95% CI, 0.236-0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR, 2.114; 95% CI, 2.004-2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype. Our findings suggest that dietary sodium intake may be causally associated with hypertension risk.

Sodium status and kidney involvement during COVID-19 infection

The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death. Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys. We propose that sodium intake and status should be monitored carefully during severe COVID-19 infections, and that low sodium intake be corrected early in its course, despite a potential conflict regarding common dietary recommendations to restrict dietary sodium intake in patients with hypertension, diabetes, and kidney disease.

The Impact of Dietary Sodium on Sympathetic and Blood Pressure Reactivity Assessed using the Cold Pressor Test

High dietary sodium intake increases sympathetic and blood pressure (BP) reactivity in rodents, but it is not known if dietary sodium similarly affects reactivity in non‐hypertensive humans. Importantly, exaggerated sympathetic and BP responses are predictive of future hypertension risk.PURPOSEWe hypothesized that high dietary sodium would increase sympathetic and BP reactivity in male and female adults. The cold pressor test (CPT) was used to assess reactivity.METHODSTwenty‐seven healthy, non‐hypertensive adults (16M/11F; age: 26±7yrs; BMI: 24.7±1 kg/m2; mean±SD) participated in a controlled feeding study that consisted of 10 days of low (LS: 1.0 g/day), recommended (MS: 2.3 g/day), or high (HS: 7.0 g/day) sodium diets, in random order with at least a one‐month washout between diets. Twenty‐four hour urine samples were collected and sodium excretion was calculated to ensure compliance on the respective diets. Muscle sympathetic nerve activity (MSNA) was directly assessed using peroneal microneurography and beat‐to‐beat BP was assessed using photoplethysmography at rest and throughout the CPT. The CPT was completed by having participants immerse their dominant hand in an ice slurry (3° to 5°C) for 2 minutes. Data were analyzed using two‐way repeated measures ANOVAs.RESULTSAs expected, twenty‐four hour sodium excretion increased with increasing amounts of dietary salt (LS: 42±40, MS: 84±36, HS: 253±111 mmol/24 hours, main effect of diet, p&lt;0.0001), with no apparent sex differences (p = 0.98). The CPT robustly increased MSNA, but there was no effect of diet (Δ MSNA burst frequency LS: 13±6, MS: 16±6, HS: 15±5 bursts/min, p = 0.23). Similarly, the CPT acutely increased systolic BP, but there was no effect of diet (Δ systolic BP LS: 18±11, MS: 20±12, HS: 18±11 mmHg, p = 0.44).CONCLUSIONThese data suggest that 10 days of high dietary salt intake does not affect MSNA or BP responses to the CPT in young, healthy, non‐hypertensive adults.Support or Funding InformationSupported by NIH Grant 1R01HL128388

Associations of Dietary Sodium, Potassium, and Sodium to Potassium Ratio with Blood Pressure- Regional Disparities in China.

High dietary sodium and low potassium intake increase blood pressure and risk of hypertension, but whether the relationship between dietary sodium and potassium and risk of hypertension is different in North China and South China remains unclear. We used data from the longitudinal China Health and Nutrition Survey (CHNS) and selected 6705 adults who participated in at least two waves in 2009, 2011, and 2015 and had no hypertension in baseline. We performed multiple linear regression analysis and multiple logistic regressions stratified by area for the present study design. Sodium and potassium intake were higher in North China (4343.4 and 1624.8 mg/day, respectively) than in South China (4107.8 and 1516.1 mg/d, respectively) (p < 0.05). Multiple linear regression revealed that a positive correlation of sodium intake (β = 0.026, p < 0.05) and ratio of sodium to potassium (Na-K) intake (β = 0.041, p < 0.01) with diastolic blood pressure (DBP) was found in North China, and the association of sodium, potassium, and Na-K intake ratio with blood pressure was different in South China. Multiple logistic regressions documented a similar significant inverse association between dietary potassium intake and risk of hypertension in both North China and South China (risk ratio (RR): 0.63, 95%CI: 0.50–0.79; RR: 0.80, 95%CI: 0.66–0.98, respectively). The risk of hypertension increased in the fourth quartile of dietary sodium and Na-K intake ratio (RR: 1.20, 95%CI: 1.00–1.44; RR: 1.35, 95%CI: 1.13–1.62, respectively) in North China but no association was observed in South China. The current study indicates a different association of dietary sodium and Na-K intake ratio with systolic blood pressure (SBP), DBP, and risk of hypertension in North China and South China.