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High Adherence to Mediterranean Diet Is Not Associated with an Improved Sodium and Potassium Intake.
Viroli, G, Gonçalves, C, Pinho, O, Silva-Santos, T, Padrão, P, Moreira, P
Nutrients. 2021;(11)
Abstract
Prevention and control of hypertension and cerebro-cardiovascular diseases are associated with adequate sodium and potassium intake and adherence to a Mediterranean dietary pattern. The aim of this study was to assess the association between adherence to a Mediterranean diet (MD) and the excretion of sodium and potassium as surrogate measures of intake. This is a cross-sectional analysis as part of a larger study (the iMC SALT randomized controlled trial) among workers of a public university. A food frequency questionnaire was used to assess the adherence to MD, using the alternative Mediterranean diet (aMED) score; sodium and potassium excretions were estimated by 24-h urine collections. Sociodemographic and other lifestyle characteristics were also obtained. The associations between the adherence to MD and Na and K excretion were calculated by logistic regression, adjusting for confounding variables. From the 109 selected participants, seven were excluded considering urine screening and completeness criteria, leaving a final sample of 102 subjects (48% male, average age 47 years). Mean sodium and potassium excretion were 3216 mg/day and 2646 mg/day, respectively. Sodium and potassium excretion were significantly higher in men, but no differences were found according to different levels of MD adherence. In logistic regression analysis, sodium, potassium, and sodium-to-potassium ratio urinary excretion tertiles were not associated with MD adherence (low/moderate versus high), even after adjustment for confounding variables. A high adherence to MD was thus not associated with a different level of sodium and potassium intake.
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Factors associated with heart failure hospitalization in patients with high sodium excretion: subanalysis of the ESPRIT, evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients, cohort study.
Sadanaga, T, Hirota, S, Mitamura, H
Heart and vessels. 2021;(1):85-91
Abstract
We have reported that high sodium excretion ≥ 4.0 g/day, assessed by repeated measurements of spot urine, is associated with composite cardiovascular (CV) events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and documented CV deaths in Japanese high-risk patients with either stable and compensated congestive HF, high brain natriuretic peptide, coronary artery disease, cerebrovascular disease, chronic kidney disease, or atrial fibrillation. A total of 520 patients were enrolled. During the median follow-up period of 5.2 years, 105 (20%) experienced composite CV events, which were predominantly driven by 60 (12%) HF hospitalizations. The aim of the present study was to elucidate which subgroups of patients with high sodium excretion were associated with HF hospitalization. We divided the enrolled patients into three groups according to the amount of sodium excretion (< 3.0 g/day, 3.0-3.99 g/day (reference), and ≥ 4.0 g/day) based on a median of 14 measurements during follow-up. We assessed the hazard ratio for HF hospitalization according to age, bodyweight, and gender, using the Cox hazard model. In the total population, high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization [hazard ratio (HR) 1.75, confidence interval (CI) 1.05-2.83] after adjustment for gender, age, and bodyweight, but was not associated with other CV events. In older patients (≥ 75 years old), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for gender and bodyweight (HR 3.25, CI 1.55-6.55), which was not observed in younger (< 75 years old) patients. In patients with lower bodyweight (< 60 kg), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for age and gender (HR 3.05, CI 1.34-6.61), which was not observed in heavier (≥ 60 kg) patients. High sodium excretion is associated with HF hospitalization in patients with older age and lower bodyweight in Japanese high-risk patients.
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Intake of processed meat, but not sodium, is associated with risk of colorectal cancer: Evidence from a large prospective cohort and two-sample Mendelian randomization.
Feng, Q, Wong, SH, Zheng, J, Yang, Q, Sung, JJ, Tsoi, KK
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4551-4559
Abstract
BACKGROUND & AIMS Processed meat and high sodium intake are common in Western diet. The objective was to examine their independent effects on the risk of colorectal cancer (CRC). METHODS We performed both observational analysis with UK Biobank and genetic analysis with Mendelian randomization (MR). The 24-h urinary sodium (UNa) and reported intake of processed meat were fitted on incident CRC by multivariable Cox proportional hazard model, adjusted for covariates, such as age, gender, family history, etc. Different sodium measures were used for sensitivity analyses. Two-sample MR analyses were performed using summary data from genome-wide association studies of UNa and CRC. Multivariable MR was adjusted for body mass index. RESULTS We included 415 524 eligible participants from UK Biobank. During a median follow-up of 11.1 years, 2663 participants were diagnosed with CRC. High intake of processed meat independently increased risk of CRC by 23% (HR 1.23; 95% CI: 1.03 to 1.46), but 24-h UNa was not significantly associated with CRC (HR 0.96; 95% CI: 0.87 to 1.06). Furthermore, MR also showed little evidence for the effect of UNa on CRC (OR 1.02; 95% CI: 0.11 to 9.42). Sensitivity analyses showed consistent results across different measurements of sodium intake. CONCLUSIONS Intake of processed meat had an independent effect on the risk of CRC, but the risk was not associated with sodium level. Reduction of processed meat intake may be an effective strategy for CRC prevention, while sodium reduction should still be recommended to achieve other health benefits.
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4.
Urine Metabolites Associated with the Dietary Approaches to Stop Hypertension (DASH) Diet: Results from the DASH-Sodium Trial.
Kim, H, Lichtenstein, AH, Wong, KE, Appel, LJ, Coresh, J, Rebholz, CM
Molecular nutrition & food research. 2021;(3):e2000695
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Abstract
SCOPE Serum metabolomic markers of the Dietary Approaches to Stop Hypertension (DASH) diet are previously reported. In an independent study, the similarity of urine metabolomic markers are investigated. METHODS AND RESULTS In the DASH-Sodium trial, participants are randomly assigned to the DASH diet or control diet, and received three sodium interventions (high, intermediate, low) within each randomized diet group in random order for 30 days each. Urine samples are collected at the end of each intervention period and analyzed for 938 metabolites. Two comparisons are conducted: 1) DASH-high sodium (n = 199) versus control-high sodium (n = 193), and 2) DASH-low sodium (n = 196) versus control-high sodium. Significant metabolites identified using multivariable linear regression are compared and the top 10 influential metabolites identified using partial least-squares discriminant analysis to the results from the DASH trial. Nine out of 10 predictive metabolites of the DASH-high sodium and DASH-low sodium diets are identical. Most candidate biomarkers from the DASH trial replicated. N-methylproline, chiro-inositol, stachydrine, and theobromine replicated as influential metabolites of DASH diets. CONCLUSIONS Candidate biomarkers of the DASH diet identified in serum replicated in urine. Replicated influential metabolites are likely to be objective biomarkers of the DASH diet.
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Sodium Intake as a Cardiovascular Risk Factor: A Narrative Review.
Jaques, DA, Wuerzner, G, Ponte, B
Nutrients. 2021;(9)
Abstract
While sodium is essential for human homeostasis, current salt consumption far exceeds physiological needs. Strong evidence suggests a direct causal relationship between sodium intake and blood pressure (BP) and a modest reduction in salt consumption is associated with a meaningful reduction in BP in hypertensive as well as normotensive individuals. Moreover, while long-term randomized controlled trials are still lacking, it is reasonable to assume a direct relationship between sodium intake and cardiovascular outcomes. However, a consensus has yet to be reached on the effectiveness, safety and feasibility of sodium intake reduction on an individual level. Beyond indirect BP-mediated effects, detrimental consequences of high sodium intake are manifold and pathways involving vascular damage, oxidative stress, hormonal alterations, the immune system and the gut microbiome have been described. Globally, while individual response to salt intake is variable, sodium should be perceived as a cardiovascular risk factor when consumed in excess. Reduction of sodium intake on a population level thus presents a potential strategy to reduce the burden of cardiovascular disease worldwide. In this review, we provide an update on the consequences of salt intake on human health, focusing on BP and cardiovascular outcomes as well as underlying pathophysiological hypotheses.
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Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet.
Gueneau de Mussy, P, Sidharta, PN, Wuerzner, G, Maillard, MP, Guérard, N, Iglarz, M, Flamion, B, Dingemanse, J, Burnier, M
Clinical pharmacology and therapeutics. 2021;(3):746-753
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Abstract
Aprocitentan is a novel, oral, dual endothelin receptor antagonist (ERA) in development in difficult-to-control hypertension. As fluid retention and edema are concerns with ERAs, we investigated whether aprocitentan causes weight gain in healthy subjects on a high sodium diet and explored potential mechanisms if occurring. This double-blind, randomized, placebo-controlled, crossover study enrolled 28 subjects. Three doses of aprocitentan (10, 25, or 50 mg/day for 9 days) were compared with placebo. Increases in body weight were observed with aprocitentan (placebo-corrected mean weight gains [90% confidence interval]) of 0.43 [0.05-0.80], 0.77 [0.03-1.51], and 0.83 [0.33-1.32] kg at 10 mg, 25 mg, and 50 mg, respectively. Decreases in hemoglobin and uric acid were observed. Plasma volume increased at most by 5.5% without dose-response relationship. Urinary sodium excretion decreased at 10 mg and 25 mg but not at 50 mg. Therefore, aprocitentan produced moderate weight increases in healthy subjects on high sodium diet, without obvious sodium retention.
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Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in Humans.
Basdeki, ED, Kollias, A, Mitrou, P, Tsirimiagkou, C, Georgakis, MK, Chatzigeorgiou, A, Argyris, A, Karatzi, K, Manios, Y, Sfikakis, PP, et al
Nutrients. 2021;(8)
Abstract
Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(-0.3, 0.4) mg/L; TNF-a -0.7(-5.0, 3.6) pg/mL; IL-6 -1.1(-3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, "normal" and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.
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Core Strategies to Increase the Uptake and Use of Potassium-Enriched Low-Sodium Salt.
Ajenikoko, A, Ide, N, Shivashankar, R, Ge, Z, Marklund, M, Anderson, C, Atun, A, Thomson, A, Henry, ME, Cobb, LK
Nutrients. 2021;(9)
Abstract
Excess sodium consumption and insufficient potassium intake contribute to high blood pressure and thus increase the risk of heart disease and stroke. In low-sodium salt, a portion of the sodium in salt (the amount varies, typically ranging from 10 to 50%) is replaced with minerals such as potassium chloride. Low-sodium salt may be an effective, scalable, and sustainable approach to reduce sodium and therefore reduce blood pressure and cardiovascular disease at the population level. Low-sodium salt programs have not been widely scaled up, although they have the potential to both reduce dietary sodium intake and increase dietary potassium intake. This article proposes a framework for a successful scale-up of low-sodium salt use in the home through four core strategies: availability, awareness and promotion, affordability, and advocacy. This framework identifies challenges and potential solutions within the core strategies to begin to understand the pathway to successful program implementation and evaluation of low-sodium salt use.
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Advances in Genomics Research of Blood Pressure Responses to Dietary Sodium and Potassium Intakes.
Razavi, MA, Bazzano, LA, Nierenberg, J, Huang, Z, Fernandez, C, Razavi, AC, Whelton, SP, He, J, Kelly, TN
Hypertension (Dallas, Tex. : 1979). 2021;(1):4-15
Abstract
More than half of US adults have hypertension by 40 years of age and a subsequent increase in atherosclerotic cardiovascular disease risk. Dietary sodium and potassium are intricately linked to the pathophysiology of hypertension. However, blood pressure responses to dietary sodium and potassium, phenomena known as salt and potassium sensitivity of blood pressure, respectively, are heterogenous and normally distributed in the general population. Like blood pressure, salt and potassium sensitivity are complex phenotypes, and previous research has shown that up to 75% of individuals experience a blood pressure change in response to such dietary minerals. Previous research has also implicated both high salt sensitivity and low salt sensitivity (or salt resistance) of blood pressure to an increased risk of hypertension and potentially atherosclerotic cardiovascular disease risk. Given the clinical challenges required to accurately measure the sodium and potassium response phenotypes, genomic characterization of these traits has become of interest for hypertension prevention initiatives on both the individual and population levels. Here, we review advances in human genomics research of blood pressure responses to dietary sodium and potassium by focusing on 3 main areas, including the phenotypic characterization of salt sensitivity and resistance, clinical challenges in diagnosing such phenotypes, and the genomic mechanisms that may help to explain salt and potassium sensitivity and resistance. Through this process, we hope to further underline the value of leveraging genomics and broader multiomics for characterizing the blood pressure response to sodium and potassium to improve precision in lifestyle approaches for primordial and primary atherosclerotic cardiovascular disease prevention.
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Effect of dietary sodium restriction on blood pressure in type 2 diabetes: A meta-analysis of randomized controlled trials.
Ren, J, Qin, L, Li, X, Zhao, R, Wu, Z, Ma, Y
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(6):1653-1661
Abstract
AIMS: Although current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) of sodium restriction and blood pressure (BP) in patients with T2DM. DATA SYNTHESIS We performed a systematic search of the online databases that evaluated the effect of dietary sodium restriction on BP in patients with T2DM. Sodium intake was expressed by 24 h urinary sodium excretion (UNaV). Q statistics and I2 were used to explore between-study heterogeneity. A random-effects model was used in the presence of significant heterogeneity; otherwise, a fixed-effects model was applied. Eight RCTs with 10 trials (7 cross-over and 3 parallel designs) were included in the meta-analysis. Compared with ordinary sodium intake, dietary sodium restriction significantly decreased UNaV (weighted mean difference, WMD: -38.430 mmol/24 h; 95% CI: -41.665 mmol/24 h to -35.194 mmol/24 h). Sodium restriction significantly lowered systolic BP (WMD: -5.574 mm Hg; 95% CI: -8.314 to -2.834 mm Hg; I2 = 0.0%) and diastolic BP (WMD: -1.675 mm Hg; 95% CI: -3.199 to -0.150 mm Hg; I2 = 0.0%) with low heterogeneity among the studies. No publication bias was found from Begg's and Egger's tests. CONCLUSIONS Sodium restriction significantly reduces SBP and DBP in patients with T2DM.