24-Hour Urinary Sodium and Potassium Excretion and Cardiovascular Risk.

BACKGROUND: The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method. METHODS: We included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis. RESULTS: Among 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94). CONCLUSIONS: Higher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).

No change in 24-h sodium intake estimated from spot urine in Norwegian adults from 2006 to 2019: the population-based Trøndelag Health Study (HUNT).

OBJECTIVE: Monitoring time trends in salt consumption is important for evaluating the impact of salt reduction initiatives on public health outcomes. There has so far not been available data to indicate if salt consumption in Norway has changed during the previous decade. We aimed to assess whether average 24-h salt intake estimated from spot urine samples in the adult population of mid-Norway changed from 2006-2008 to 2017-2019 and to describe variations by sex, age and educational level. DESIGN: Repeated cross-sectional studies. SETTING: The population-based Trøndelag Health Study (HUNT). PARTICIPANTS: In each of two consecutive waves (HUNT3: 2006-2008 and HUNT4: 2017-2019), spot urine samples were collected from 500 men and women aged 25-64 years, in addition to 250 men and women aged 70-79 years in HUNT4. Based on spot urine concentrations of Na, K and creatinine and age, sex and BMI, we estimated 24-h Na intake using the International Cooperative Study on Salt and Blood Pressure (INTERSALT) equation for the Northern European region. RESULTS: Mean (95 % CI) estimated 24-h salt intakes in men were 11·1 (95 % CI 10·8, 11·3) g in HUNT3 and 10·9 (95 % CI 10·6, 11·1) g in HUNT4, P = 0·25. Corresponding values in women were 7·7 (95 % CI 7·5, 7·9) g and 7·7 (95 % CI 7·5, 7·9) g, P = 0·88. Mean estimated salt intake in HUNT4 decreased with increasing age in women, but not in men, and it did not differ significantly across educational level in either sex. CONCLUSIONS: Estimated 24-h salt intake in adult men and women in mid-Norway did not change from 2006-2008 to 2017-2019.

An in vivo protein landscape of the mouse DCT during high dietary K+ or low dietary Na+ intake.

The hormone aldosterone is essential for maintaining K+ and Na+ balance and controlling blood pressure. Aldosterone has different effects if it is secreted due to hypovolemia or hyperkalemia. The kidney distal convoluted tubule (DCT) is believed to play a central role in mediating the differential responses to aldosterone. To determine the alterations in the DCT that may be responsible for these effects, male mice with green fluorescent protein expression specifically in the DCT were maintained on diets containing low NaCl (hypovolemic state) or high potassium citrate (hyperkalemic state) for 4 days, and DCT cells were isolated using fluorescence-activated cell sorting. This pure population of DCT cells was subjected to analysis by liquid chromatography-coupled tandem mass spectrometry. Over 3,000 proteins were identified in the DCT, creating the first proteome of the mouse DCT. Of the identified proteins, 210 proteins were altered in abundance following a low-NaCl diet and 625 proteins following the high-K+ diet. Many of these changes were not detectable by analyzing whole kidney samples from the same animals. When comparing responses to high-K+ versus low-Na+ diets, protein translation, chaperone-mediated protein folding, and protein ubiquitylation were likely to be significantly altered in the DCT subsequent to a high-K+ diet. In conclusion, this study defines an in vivo protein landscape of the DCT in male mice following either a low-NaCl or a high-K+ diet and acts as an essential resource for the kidney research community.NEW & NOTEWORTHY The mineralocorticoid aldosterone, essential for maintaining body K+ and Na+ balance, has different effects if secreted due to hypovolemia or hyperkalemia. Here, we used proteomics to profile kidney distal convoluted tubule (DCT) cells isolated by a novel FACS approach from mice fed a low-Na+ diet (mimicking hypovolemia) or a high-K+ diet (mimicking hyperkalemia). The study provides the first in-depth proteome of the mouse DCT and insights into how it is physiologically regulated.

Deletion of Kir5.1 abolishes the effect of high Na+ intake on Kir4.1 and Na+-Cl- cotransporter.

High sodium (HS) intake inhibited epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron and Na+-Cl- cotransporter (NCC) by suppressing basolateral Kir4.1/Kir5.1 in the distal convoluted tubule (DCT), thereby increasing renal Na+ excretion but not affecting K+ excretion. The aim of the present study was to explore whether deletion of Kir5.1 compromises the inhibitory effect of HS on NCC expression/activity and renal K+ excretion. Patch-clamp experiments demonstrated that HS failed to inhibit DCT basolateral K+ channels and did not depolarize K+ current reversal potential of the DCT in Kir5.1 knockout (KO) mice. Moreover, deletion of Kir5.1 not only increased the expression of Kir4.1, phospho-NCC, and total NCC but also abolished the inhibitory effect of HS on the expression of Kir4.1, phospho-NCC, and total NCC and thiazide-induced natriuresis. Also, low sodium-induced stimulation of NCC expression/activity and basolateral K+ channels in the DCT were absent in Kir5.1 KO mice. Deletion of Kir5.1 decreased ENaC currents in the late DCT, and HS further inhibited ENaC activity in Kir5.1 KO mice. Finally, measurement of the basal renal K+ excretion rate with the modified renal clearance method demonstrated that long-term HS inhibited the renal K+ excretion rate and steadily increased plasma K+ levels in Kir5.1 KO mice but not in wild-type mice. We conclude that Kir5.1 plays an important role in mediating the effect of HS intake on basolateral K+ channels in the DCT and NCC activity/expression. Kir5.1 is involved in maintaining renal ability of K+ excretion during HS intake. NEW & NOTEWORTHY Kir5.1 plays an important role in mediating the effect of high sodium intake on basolateral K+ channels in the distal convoluted tubule and Na+-Cl- cotransporter activity/expression.

Deletion of renal Nedd4-2 abolishes the effect of high sodium intake (HS) on Kir4.1, ENaC, and NCC and causes hypokalemia during high HS.

Neural precursor cell expressed developmentally downregulated protein 4-2 (Nedd4-2) regulates the expression of Kir4.1, thiazide-sensitive NaCl cotransporter (NCC), and epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN), and Nedd4-2 deletion causes salt-sensitive hypertension. We now examined whether Nedd4-2 deletion compromises the effect of high-salt (HS) diet on Kir4.1, NCC, ENaC, and renal K+ excretion. Immunoblot analysis showed that HS diet decreased the expression of Kir4.1, Ca2+-activated large-conductance K+ channel subunit-α (BKα), ENaCß, ENaCγ, total NCC, and phospho-NCC (at Thr53) in floxed neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4lfl/fl) mice, whereas these effects were absent in kidney-specific Nedd4-2 knockout (Ks-Nedd4-2 KO) mice. Renal clearance experiments also demonstrated that Nedd4-2 deletion abolished the inhibitory effect of HS diet on hydrochlorothiazide-induced natriuresis. Patch-clamp experiments showed that neither HS diet nor low-salt diet had an effect on Kir4.1/Kir5.1 currents of the distal convoluted tubule in Nedd4-2-deficient mice, whereas we confirmed that HS diet inhibited and low-salt diet increased Kir4.1/Kir5.1 activity in Nedd4lflox/flox mice. Nedd4-2 deletion increased ENaC currents in the ASDN, and this increase was more robust in the cortical collecting duct than in the distal convoluted tubule. Also, HS-induced inhibition of ENaC currents in the ASDN was absent in Nedd4-2-deficient mice. Renal clearance experiments showed that HS intake for 2 wk increased the basal level of renal K+ excretion and caused hypokalemia in Ks-Nedd4-2-KO mice but not in Nedd4lflox/flox mice. In contrast, plasma Na+ concentrations were similar in Nedd4lflox/flox and Ks-Nedd4-2 KO mice on HS diet. We conclude that Nedd4-2 plays an important role in mediating the inhibitory effect of HS diet on Kir4.1, ENaC, and NCC and is essential for maintaining normal renal K+ excretion and plasma K+ ranges during long-term HS diet.NEW & NOTEWORTHY The present study suggests that Nedd4-2 is involved in mediating the inhibitory effect of high salt (HS) diet on Kir4.1/kir5.1 in the distal convoluted tubule, NaCl cotransporter function, and epithelial Na+ channel activity and that Nedd4-2 plays an essential role in maintaining K+ homeostasis in response to a long-term HS diet. This suggests the possibility that HS intake could lead to hypokalemia in subjects lacking proper Nedd4-2 E3 ubiquitin ligase activity in aldosterone-sensitive distal nephron.

Policy Progress in Reducing Sodium in the American Diet, 2010-2019.

Most Americans consume dietary sodium exceeding age-specific government-recommended targets of 1,500-2,300 mg/day per person. The majority (71%) of US dietary sodium comes from restaurant and packaged foods. Excess sodium intake contributes to hypertension and cardiovascular disease, which is the leading cause of death in the United States. This review summarizes evidence for policy progress to reduce sodium in the US food supply and the American diet. We provide a historical overview of US sodium-reduction policy (1969-2010), then examine progress toward implementing the 2010 National Academy of Medicine (NAM) sodium report's recommendations (2010-2019). Results suggest that the US Food and Drug Administration made no progress in setting mandatory sodium-reduction standards, industry made some progress in meeting voluntary targets, and other stakeholders made some progress on sodium-reduction actions. Insights from countries that have significantly reduced population sodium intake offer strategies to accelerate US progress toward implementing the NAM sodium-reduction recommendations in the future.

Dissociable effects of dietary sodium in early life upon somatic growth, fluid homeostasis, and spatial memory in mice of both sexes.

Postnatal growth failure is a common morbidity for preterm infants and is associated with adverse neurodevelopmental outcomes. Although sodium (Na) deficiency early in life impairs somatic growth, its impact on neurocognitive functions has not been extensively studied. We hypothesized that Na deficiency during early life is sufficient to cause growth failure and program neurobehavioral impairments in later life. C57BL/6J mice were placed on low- (0.4), normal- (1.5), or high- (3 g/kg) Na chow at weaning (PD22) and continued on the diet for 3 wk (to PD40). Body composition and fluid distribution were determined serially by time-domain NMR and bioimpedance spectroscopy, and anxiety, learning, and memory were assessed using the elevated plus maze and Morris water maze paradigms in later adulthood (PD63-PD69). During the diet intervention, body mass gains were suppressed in the low- compared with normal- and high-Na groups despite similar caloric uptake rates across groups. Fat mass was reduced in males but not in females fed low-Na diet. Fat-free mass and hydration were significantly reduced in both males and females fed the low-Na diet, although rapidly corrected after return to normal diet. Measures of anxiety-like behavior and learning in adulthood were not affected by diet in either sex, yet memory performance was modified by a complex interaction between sex and early life Na intake. These data support the concepts that Na deficiency impairs growth and that the amount of Na intake which supports optimal somatic growth during early life may be insufficient to fully support neurocognitive development.

Trehalose, a natural disaccharide, reduces stroke occurrence in the stroke-prone spontaneously hypertensive rat.

Cerebrovascular disease, a frequent complication of hypertension, is a major public health issue for which novel therapeutic and preventive approaches are needed. Autophagy activation is emerging as a potential therapeutic and preventive strategy toward stroke. Among usual activators of autophagy, the natural disaccharide trehalose (TRE) has been reported to be beneficial in preclinical models of neurodegenerative diseases, atherosclerosis and myocardial infarction. In this study, we tested for the first time the effects of TRE in the stroke-prone spontaneously hypertensive rat (SHRSP) fed with a high-salt stroke permissive diet (JD). We found that TRE reduced stroke occurrence and renal damage in high salt-fed SHRSP. TRE was also able to decrease systolic blood pressure. Through ex-vivo studies, we assessed the beneficial effect of TRE on the vascular function of high salt-fed SHRSP. At the molecular level, TRE restored brain autophagy and reduced mitochondrial mass, along with the improvement of mitochondrial function. The beneficial effects of TRE were associated with increased nuclear translocation of TFEB, a transcriptional activator of autophagy. Our results suggest that TRE may be considered as a natural compound efficacious for the prevention of hypertension-related target organ damage, with particular regard to stroke and renal damage.

Temporal Trends in Dietary Sodium Intake Among Adults Aged ≥19 Years - United States, 2003-2016.

Hypertension, which can be brought on by excess sodium intake, affects nearly one half of U.S. adults and is a major risk factor for heart disease, the leading cause of death in the United States (1). In 2019, the National Academies of Sciences, Engineering, and Medicine (NASEM) established the Chronic Disease Risk Reduction (CDRR) intake, a chronic-disease-specific recommendation for dietary sodium of 2,300 mg/day. Reducing daily sodium to CDRR intake is expected to reduce chronic disease risk among healthy persons, primarily by lowering blood pressure (2). Although the 2019 sodium CDRR intake is equivalent in number to the 2005 Tolerable Upper Limit (UL) released by NASEM (then known as the Institute of Medicine), the UL was intended to provide guidance on safe intake levels, not to serve as an intake goal (2). To describe excess sodium intake in the context of the CDRR intake goal, this report analyzed National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2016 to yield temporal trends in usual sodium intake >2,300 mg/day and in mean sodium intake, unadjusted and adjusted for total energy intake, among U.S. adults aged ≥19 years. The percentage of U.S. adults with sodium intake above CDRR intake was 87.0% during 2003-2004 and 86.7% during 2015-2016. Among U.S. adults overall, no significant linear trend was noted from 2003 to 2016 in unadjusted or energy intake-adjusted mean sodium intake. Small, significant declines were observed in mean usual sodium intake among some groups (adults aged 19-50 years, non-Hispanic White adults, adults experiencing obesity, and adults without hypertension). However, after energy adjustment, only adults aged ≥71 years and Mexican American adults demonstrated significant change in usual sodium intake. Many U.S. adults might be at risk for chronic disease associated with sodium intake above CDRR intake, and efforts to lower sodium intake could improve population cardiovascular health. The results of this report support enhanced efforts to reduce population sodium intake and cardiovascular disease risk, including the Food and Drug Administration's (FDA's) recently released guidance for the reduction of sodium in the commercially processed, packaged, and prepared food supply.

Estimation of sodium and potassium intakes assessed by two 24-hour urine collections in a city of Indonesia.

Intakes of excess Na and insufficient K are two major contributors of heart diseases and stroke development. However, no precise study has previously been carried out on Na and K intakes among Indonesian adults. The present study aimed to estimate the Na and K intakes using two consecutive 24-h urine collections. Participants were community-dwelling adults aged between 20 and 96 years, randomly selected from a pool of resident registration numbers. Of the 506 participants, 479 (240 men and 239 women) completed urine collections. The mean Na excretion was 102·8 and 100·6 mmol/d, while the mean K excretion was 25·0 and 23·4 mmol/d for men and women, respectively. Na and K excretions were higher in participants with a higher BMI. A higher K excretion was associated only with younger age. More than 80 % of the participants consumed more than 5 g/d of salt (the upper limit recommended by the Indonesian government), whereas none of them consumed more than 3510 mg/d of K (the lower limit). The high Na and low K intakes, especially high Na among participants with high BMI, should be considered when future intervention programmes are planned in this country.

The association between dietary sodium intake, adiposity and sugar-sweetened beverages in children and adults: a systematic review and meta-analysis.

Higher intakes of Na may contribute to weight gain. The primary aim of this systematic review and meta-analysis was to examine the relationship between dietary Na intake and measures of adiposity in children and adults. Given the previous link between Na intake and the consumption of sugar-sweetened beverages (SSB), which are a known risk factor for obesity, a secondary aim examining the relationship between Na intake and SSB consumption was assessed. A systematic literature search identified cross-sectional and longitudinal studies and randomised controlled trials (RCT) which reduced dietary Na (≥3 months). Meta-analysis was performed for outcomes with ≥3 studies. Cross-sectionally higher Na intakes were associated with overweight/obesity in adults (five studies; n 11 067; OR 1·74; 95 % CI 1·43, 2·13) and in children (three studies; n 3625, OR 3·29; 95 % CI 2·25, 4·80), and abdominal obesity (five studies; n 19 744; OR 2·04; 95 % CI 1·72, 2·42) in adults. Overall, associations remained in sensitivity analyses which adjusted for energy. Findings from longitudinal studies were inconsistent. RCT in adults indicated a trend for lower body weight on reduced-Na compared with control diets (fifteen studies; n 5274; -0·29 kg; 95 % CI -0·59, 0·01; P = 0·06); however, it is unclear if energy intakes were also altered on reduced-Na diets. Among children higher Na intakes were associated with higher intake of SSB (four studies, n 10 329, b = 22, 16 and 26 g/d); no studies were retrieved for adults. Overall, there was a lack of high-quality studies retrieved. While cross-sectional evidence indicates Na intake was positively associated with adiposity, these findings have not been clearly confirmed by longitudinal studies or RCT.

Maturational changes in sodium metabolism in periviable infants.

BACKGROUND: Sodium depletion results in impaired somatic growth. The sodium requirements of extremely preterm (periviable) infants early in life are not known. We therefore investigated sodium homeostasis in this population over the first 10 weeks following birth. METHODS: This was a longitudinal, observational study of sodium intake and urine sodium excretion in a convenience cohort of 23 infants born at 22 0/7-23 6/7-week gestation. RESULTS: Sodium intake ranged from 5.2 ± 0.4 to a maximum of 7.9 ± 0.5 mEq/kg/day at 2 and 8 weeks of postnatal age, respectively, while urinary sodium loss was 7.7 ± 1.0 mEq/kg/day and 6.9 ± 0.7 mEq/kg/day at these time points. Sodium balance (sodium intake - urine sodium output) was first positive at 6 weeks of age, though a positive sodium balance exceeding 1.4 mEq/kg/day (i.e., a balance associated with weight gain of 30 g/day) was not observed until 10 weeks. CONCLUSIONS: Infants born at 22-23-week gestational age have a prolonged period of high urinary losses of sodium and negative sodium balance. Sodium intakes greater than those currently recommended by the American Academy of Pediatrics are needed to achieve a significant positive sodium balance in this population.

Global burden attributable to high sodium intake from 1990 to 2019.

BACKGROUND AND AIMS: High sodium intake is associated with a higher risk of a wide range of diseases. We aimed to estimate the pattern and trend of the global disease burden associated with high sodium intake from 1990 to 2019. METHODS AND RESULTS: We obtained numbers and rates of death and disability-adjusted life year (DALY) attributable to high sodium intake by sex, socio-demographic index, and country from the Global Burden of Disease Study 2019. We calculated the estimated annual percentage change to evaluate the age-standardized rate (ASR) of the burden attributable to high sodium intake between 1990 and 2019. We further calculated the contribution of population growth, population aging, and age-specific rates of death and DALY to the net change in the total number of deaths and DALYs attributable to high sodium intake. From 1990 to 2019, global age-standardized rates of death and DALY attributable to high sodium intake substantially decreased for both sexes. However, there were significant increases in the total numbers of deaths and DALYs attributable to high sodium intake, which were driven by population growth and population aging. The attribution of population growth and population aging varied widely across countries, with a higher contribution of population growth in most developing countries and a higher contribution of population aging in countries with slow population growth. CONCLUSIONS: Although the global burden attributable to high sodium intake in terms of age-standardized rate declined from 1990 to 2019, the absolute burden increased significantly, which was driven by population growth and population aging.

Mineralocorticoid receptor modulation by dietary sodium influences NAFLD development in mice.

INTRODUCTION AND OBJECTIVES: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD. MATERIALS AND METHODS: C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed. RESULTS: Mice fed with High-Na+/HFD showed a lower MR expression in liver (p = 0.01) and less steatosis on histology (p = 0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p = 0.028) and lower hepatic triglyceride content (p = 0.008). This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p < 0.05), and lower expression of pro-inflammatory and profibrotic markers compared to those mice fed a Low-Na+/HFD. Additionally, mice fed a High-Na+/HFD showed higher expression of salt-inducible kinase (SIK)-1 and lower expression of serum-and-glucocorticoid-inducible kinase (SGK)-1. Similar results were observed with the MCD diet model. CONCLUSION: We identified in two experimental models of NAFLD that High-Na+ diet content is associated to lower serum aldosterone levels and hepatic MR downregulation, associated to decreased steatosis and reduced de novo hepatic lipogenesis, proinflammatory and profibrotic markers. Decreased activation of hepatic MR seems to generate beneficial downstream inhibition of lipogenesis in experimental NAFLD.

Reducing Sodium Intake in Community Meals Programs: Evaluation of the Sodium Reduction in Communities Program, Arkansas, 2016-2019.

The Sodium Reduction in Communities Program (SRCP) aims to reduce dietary sodium intake through policy, systems, and environmental approaches. We evaluated progress of 3 years of SRCP activities in 3 community meals programs in northwest Arkansas. These activities sought to reduce dietary sodium intake through implementation of 1) food service guidelines, 2) procurement practices, 3) food preparation practices, and 4) environmental strategies. Mean reductions of 579 mg (-40%) in sodium served per diner and 525 mg (-22%) in sodium per 1,000 kcal served per diner were found from baseline to Year 1. Mean reductions of 499 mg (-35%) in sodium served per diner and 372 mg (-16%) in sodium per 1,000 kcal served per diner were sustained from baseline to Year 3. These results highlight the effectiveness and sustainability of sodium reduction interventions in community meals programs, whose diners experience food insecurity, have low incomes, and are at high risk for hypertension.

Cardiovascular Risk Factors in Young Adolescents: Results from the National Health and Nutrition Examination Survey 1988-2016.

OBJECTIVES: Lifestyle behaviors relevant to cardiovascular health are learned during childhood and continued into adulthood. Children and adolescents who participate in unhealthy behaviors have a higher lifetime risk of cardiovascular disease in adulthood. Public health institutions publish behavior and clinical recommendations designed for adolescents to reduce their lifetime cardiovascular risk. We assessed the prevalence and trends of cardiovascular-relevant behaviors and clinical tests among early adolescents using a nationally representative database. METHODS: In 2020, we compared the prevalence of cardiovascular risk factors among 1408 adolescents surveyed from 1988 to 1994 with that of 1812 adolescents surveyed from 2011 to 2016 by obtaining and comparing measures on physical activity, diet, body mass index, smoking status, cholesterol levels, hemoglobin A1c, sodium intake, and blood pressure. RESULTS: The prevalence of adherence to the current recommendations regarding physical activity, diet, and body weight declined over time. Conversely, the prevalence of adhering to recommendations to avoid smoking increased. Clinical indicators, including blood pressure control and normal measures of hemoglobin A1c and total serum cholesterol, showed mixed results, with more individuals showing signs of hyperglycemia, fewer showing signs of hypercholesterolemia, and the percentage of individuals with abnormal blood pressure remaining the same. The use of cardiometabolic medications also increased during the study period. Finally, the number of adolescents with all seven cardiovascular protective factors declined significantly during the study period, from 27.6% to 9.6%. CONCLUSIONS: Modern American teenagers aged 12 to 16 years have more cardiovascular risk factors relating mostly to diet, exercise, and obesity than those of a prior generation; however, smoking rates have also declined precipitously.

Sodium Intake during Pregnancy, but Not Other Diet Recommendations Aimed at Preventing Cardiovascular Disease, Is Positively Related to Risk of Hypertensive Disorders of Pregnancy.

BACKGROUND: The role of diet on hypertensive disorders of pregnancy (HDPs), including preeclampsia and gestational hypertension (GHTN), remains unclear. OBJECTIVES: We evaluated whether adherence during pregnancy to dietary recommendations that reduce cardiovascular disease (CVD) in the general population is related to the risk of HDPs. METHODS: We followed 66,651 singleton pregnancies from 62,774 women participating in the Danish National Birth Cohort. Diet was assessed during week of gestation 25 with an FFQ from which we created 2 dietary pattern scores: 1) AHA, based on the diet recommendations from the AHA 2020 Strategic Impact Goals; and 2) the Dietary Approaches to Stop Hypertension (DASH) diet. Cases of HDPs were identified through linkage with the Danish National Patient Registry. RRs and 95% CIs of HDPs were estimated by increasing quintiles of adherence to the AHA and DASH scores using log-Poisson regression models with generalized estimating equations-to account for repeated pregnancies per woman-while adjusting for potential confounders. RESULTS: We identified 1809 cases of HDPs: n = 1310 preeclampsia (n = 300 severe preeclampsia) and n = 499 cases of GHTN. Greater adherence to AHA or DASH scores was not related to the risk of HDPs. However, when each component of the scores was separately evaluated, there were positive linear relations of sodium intake with HDPs (P-linearity < 0.01). Women with the highest sodium intake [median 3.70 g/d (range: 3.52, 7.52 g/d)] had 54% (95% CI:16%, 104%) higher risk of GHTN and 20% (95% CI:1%, 42%) higher risk of preeclampsia than women with the lowest intake [median 2.60 g/d (range: 0.83, 2.79 g/d)]. In addition, intake of whole grains was positively related to the risk of GHTN but not to preeclampsia ( P-heterogeneity = 0.002). CONCLUSION: Sodium intake during pregnancy, but no other diet recommendations to prevent CVD among nonpregnant adults, is positively related to the occurrence of HDPs among pregnant Danish women.

Genome-Wide Association Meta-Analysis of Individuals of European Ancestry Identifies Suggestive Loci for Sodium Intake, Potassium Intake, and Their Ratio Measured from 24-Hour or Half-Day Urine Samples.

BACKGROUND: Excess sodium intake and insufficient potassium intake are risk factors for hypertension, but there is limited knowledge regarding genetic factors that influence intake. Twenty-hour or half-day urine samples provide robust estimates of sodium and potassium intake, outperforming other measures such as spot urine samples and dietary self-reporting. OBJECTIVE: The aim of this study was to investigate genomic regions associated with sodium intake, potassium intake, and sodium-to-potassium ratio measured from 24-h or half-day urine samples. METHODS: Using samples of European ancestry (mean age: 54.2 y; 52.3% women), we conducted a meta-analysis of genome-wide association studies in 4 cohorts with 24-h or half-day urine samples (n = 6,519), followed by gene-based analysis. Suggestive loci (P < 10-6) were examined in additional European (n = 844), African (n = 1,246), and Asian (n = 2,475) ancestry samples. RESULTS: We found suggestive loci (P < 10-6) for all 3 traits, including 7 for 24-h sodium excretion, 4 for 24-h potassium excretion, and 4 for sodium-to-potassium ratio. The most significant locus was rs77958157 near cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) , a gene involved in eating behavior and appetite regulation (P = 2.3 × 10-8 with sodium-to-potassium ratio). Two suggestive loci were replicated in additional samples: for sodium excretion, rs12094702 near zinc finger SWIM-type containing 5 (ZSWIM5) was replicated in the Asian ancestry sample reaching Bonferroni-corrected significance (P = 0.007), and for potassium excretion rs34473523 near sodium leak channel (NALCN) was associated at a nominal P value with potassium excretion both in European (P = 0.043) and African (P = 0.043) ancestry cohorts. Gene-based tests identified 1 significant gene for sodium excretion, CDC42 small effector 1 (CDC42SE1), which is associated with blood pressure regulation. CONCLUSIONS: We identified multiple suggestive loci for sodium and potassium intake near genes associated with eating behavior, nervous system development and function, and blood pressure regulation in individuals of European ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake.

Dietary Potassium Intake Remains Low and Sodium Intake Remains High, and Most Sodium is Derived from Home Food Preparation for Chinese Adults, 1991-2015 Trends.

BACKGROUND: Intervention strategies to reduce sodium intake and increase potassium intake may decrease blood pressure; however, most are focused on reducing sodium in processed food globally. OBJECTIVES: We attempt to fill important gaps in understanding the dynamics of these dietary determinants of hypertension in China. METHODS: We used data on 29,926 adults aged ≥20 y between 1991 and 2015 from an ongoing cohort, the China Health and Nutrition Survey. We collected detailed diet data with use of weighing methods with 3 consecutive 24-h recalls. With panel data random-effects models, we analyzed factors associated with sodium and potassium intakes and sodium to potassium (Na/K) ratios. RESULTS: Sodium intake decreased from 6.3 g/d in 1991 to 4.1 g/d in 2015, still twice the tolerable upper intake recommended by the WHO. Potassium intake was 1.7 g/d in 1991 and 1.5 g/d in 2015, below half that recommended by the WHO. The Na/K ratio decreased from 4.1 (ratios in g) in 1991 to 3.1 in 2015, 5 times the recommendation of the WHO. More than two-thirds (67%) of sodium intake was from salt added during food preparation, with 8.8% from processed foods in 2015, up from 5.0% in 1991. The most at-risk populations lived in China's central region and rural areas, were middle aged, had lower educations, or were farmers. CONCLUSIONS: Sodium intake is very high across all regions in China. As part of sodium reduction efforts, China should target people living in the central region and adults aged above 60 whose sodium intakes are much higher. Strategies to decrease sodium intake and increase potassium intake should be different from those applied in the Western world where the major source is processed food. Reduced sodium higher potassium salts should become a major policy initiative in China.

Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide.

BACKGROUND: While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking. OBJECTIVES: We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms. METHODS: We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger). RESULTS: Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01). CONCLUSIONS: These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555.