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JAMA Dec 2023Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among... (Clinical Trial)
Clinical Trial
IMPORTANCE
Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied.
OBJECTIVES
To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use.
DESIGN, SETTING, AND PARTICIPANTS
Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets.
INTERVENTION
High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets.
MAIN OUTCOMES AND MEASURES
Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure.
RESULTS
Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively.
CONCLUSIONS AND RELEVANCE
Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04258332.
Topics: Aged; Female; Humans; Male; Middle Aged; Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Diet, Sodium-Restricted; Hypertension; Sodium; Sodium Chloride, Dietary; Sodium, Dietary
PubMed: 37950918
DOI: 10.1001/jama.2023.23651 -
BMJ (Clinical Research Ed.) Aug 2023To determine the effects of salt reduction interventions designed for home cooks and family members. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the effects of salt reduction interventions designed for home cooks and family members.
DESIGN
Cluster randomised controlled trial.
SETTING
Six provinces in northern, central, and southern China from 15 October 2018 to 30 December 2019.
PARTICIPANTS
60 communities from six provinces (10 communities from each province) were randomised; each community comprised 26 people (two people from each of 13 families).
INTERVENTIONS
Participants in the intervention group received 12 month interventions, including supportive environment building for salt reduction, six education sessions on salt reduction, and salt intake monitoring by seven day weighed record of salt and salty condiments. The control group did not receive any of the interventions.
MAIN OUTCOME MEASURE
Difference between the two groups in change in salt intake measured by 24 hour urinary sodium during the 12 month follow-up.
RESULTS
1576 participants (775 (49.2%) men; mean age 55.8 (standard deviation 10.8) years) from 788 families (one home cook and one other adult in each family) completed the baseline assessment. After baseline assessment, 30 communities with 786 participants were allocated to the intervention group and 30 communities with 790 participants to the control group. During the trial, 157 (10%) participants were lost to follow-up, and the remaining 706 participants in the intervention group and 713 participants in the control group completed the follow-up assessment. During the 12 month follow-up, the urinary sodium excretion decreased from 4368.7 (standard deviation 1880.3) mg per 24 hours to 3977.0 (1688.8) mg per 24 hours in the intervention group and from 4418.7 (1973.7) mg per 24 hours to 4330.9 (1859.8) mg per 24 hours in the control group. Compared with the control group, adjusted mixed linear model analysis showed that the 24 hour urinary sodium excretion in the intervention group was reduced by 336.8 (95% confidence interval 127.9 to 545.7) mg per 24 hours (P=0.002); the systolic and diastolic blood pressures were reduced by 2.0 (0.4 to 3.5) (P=0.01) and 1.1 (0.1 to 2.0) mm Hg (P=0.03), respectively; and the knowledge, attitude, and behaviours in the intervention group improved significantly.
CONCLUSIONS
The community based salt reduction package targeting home cooks and family members was effective in lowering salt intake and blood pressure. This intervention has the potential to be widely applied in China and other countries where home cooking remains a major source of salt intake.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR1800016804.
Topics: Adult; Male; Humans; Middle Aged; Female; Sodium Chloride, Dietary; Family; China; Cooking; Sodium
PubMed: 37620015
DOI: 10.1136/bmj-2022-074258 -
International Journal of Molecular... Aug 2023Melanoma-associated antigen D2 (MAGED2) plays an essential role in activating the cAMP/PKA pathway under hypoxic conditions, which is crucial for stimulating renal salt...
Melanoma-associated antigen D2 (MAGED2) plays an essential role in activating the cAMP/PKA pathway under hypoxic conditions, which is crucial for stimulating renal salt reabsorption and thus explaining the transient variant of Bartter's syndrome. The cAMP/PKA pathway is also known to regulate autophagy, a lysosomal degradation process induced by cellular stress. Previous studies showed that two members of the melanoma-associated antigens MAGE-family inhibit autophagy. To explore the potential role of MAGED2 in stress-induced autophagy, specific MAGED2-siRNA were used in HEK293 cells under physical hypoxia and oxidative stress (cobalt chloride, hypoxia mimetic). Depletion of MAGED2 resulted in reduced p62 levels and upregulation of both the autophagy-related genes (ATG5 and ATG12) as well as the autophagosome marker LC3II compared to control siRNA. The increase in the autophagy markers in MAGED2-depleted cells was further confirmed by leupeptin-based assay which concurred with the highest LC3II accumulation. Likewise, under hypoxia, immunofluorescence in HEK293, HeLa and U2OS cell lines demonstrated a pronounced accumulation of LC3B puncta upon MAGED2 depletion. Moreover, LC3B puncta were absent in human fetal control kidneys but markedly expressed in a fetal kidney from a MAGED2-deficient subject. Induction of autophagy with both physical hypoxia and oxidative stress suggests a potentially general role of MAGED2 under stress conditions. Various other cellular stressors (brefeldin A, tunicamycin, 2-deoxy-D-glucose, and camptothecin) were analyzed, which all induced autophagy in the absence of MAGED2. Forskolin (FSK) inhibited, whereas GNAS Knockdown induced autophagy under hypoxia. In contrast to other MAGE proteins, MAGED2 has an inhibitory role on autophagy only under stress conditions. Hence, a prominent role of MAGED2 in the regulation of autophagy under stress conditions is evident, which may also contribute to impaired fetal renal salt reabsorption by promoting autophagy of salt-transporters in patients with MAGED2 mutation.
Topics: Humans; HEK293 Cells; Autophagy; Oxidative Stress; Autophagosomes; Sodium Chloride; Sodium Chloride, Dietary; Melanoma; Antigens, Neoplasm; Adaptor Proteins, Signal Transducing
PubMed: 37686237
DOI: 10.3390/ijms241713433 -
Hypertension (Dallas, Tex. : 1979) Jun 2024Salt-sensitive hypertension (SS-HT) is characterized by blood pressure elevation in response to high dietary salt intake and is considered to increase the risk of... (Review)
Review
Salt-sensitive hypertension (SS-HT) is characterized by blood pressure elevation in response to high dietary salt intake and is considered to increase the risk of cardiovascular and renal morbidity. Although the mechanisms responsible for SS-HT are complex, the kidneys are known to play a central role in the development of SS-HT and the salt sensitivity of blood pressure (SSBP). Moreover, several factors influence renal function and SSBP, including the renin-angiotensin-aldosterone system, sympathetic nervous system, obesity, and aging. A phenotypic characteristic of SSBP is aberrant activation of the renin-angiotensin system and sympathetic nervous system in response to excessive salt intake. SSBP is also accompanied by a blunted increase in renal blood flow after salt loading, resulting in sodium retention and SS-HT. Obesity is associated with inappropriate activation of the aldosterone mineralocorticoid receptor pathway and renal sympathetic nervous system in response to excessive salt, and mineralocorticoid receptor antagonists and renal denervation attenuate sodium retention and inhibit salt-induced blood pressure elevation in obese dogs and humans. SSBP increases with age, which has been attributed to impaired renal sodium handling and a decline in renal function, even in the absence of kidney disease. Aging-associated changes in renal hemodynamics are accompanied by significant alterations in renal hormone levels and renal sodium handling, resulting in SS-HT. In this review, we focus mainly on the contribution of renal function to the development of SS-HT.
Topics: Humans; Hypertension; Kidney; Sodium Chloride, Dietary; Renin-Angiotensin System; Sympathetic Nervous System; Animals; Blood Pressure; Obesity; Aging
PubMed: 38545804
DOI: 10.1161/HYPERTENSIONAHA.123.21369 -
Advances in Nutrition (Bethesda, Md.) Feb 2024
Topics: Humans; Iodine; Sodium Chloride, Dietary
PubMed: 38185218
DOI: 10.1016/j.advnut.2024.100168 -
Kidney International Oct 2023A high dietary sodium-consumption level is considered the most important lifestyle factor that can be modified to help prevent an increase in blood pressure and the...
A high dietary sodium-consumption level is considered the most important lifestyle factor that can be modified to help prevent an increase in blood pressure and the development of hypertension. Despite numerous studies over the past decades, the pathophysiology explaining why some people show a salt-sensitive blood pressure response and others do not is incompletely understood. Here, a brief overview of the latest mechanistic insights is provided, focusing on the mononuclear phagocytic system and inflammation, the gut-kidney axis, and epigenetics. The article also discusses the effects of 3 types of novel drugs on salt-sensitive hypertension-sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and aldosterone synthase inhibitors. The conclusion is that besides kidney-centered mechanisms, vasoconstrictor mechanisms are also relevant for both the understanding and treatment of this blood pressure phenotype.
Topics: Humans; Aldosterone; Blood Pressure; Hypertension; Mineralocorticoid Receptor Antagonists; Receptors, Mineralocorticoid; Sodium Chloride, Dietary
PubMed: 37454911
DOI: 10.1016/j.kint.2023.06.035 -
Hypertension (Dallas, Tex. : 1979) Mar 2024Salt sensitivity concerns blood pressure alterations after a change in salt intake (sodium chloride). The heart is a pump, and vessels are tubes; sodium can affect both.... (Review)
Review
Salt sensitivity concerns blood pressure alterations after a change in salt intake (sodium chloride). The heart is a pump, and vessels are tubes; sodium can affect both. A high salt intake increases cardiac output, promotes vascular dysfunction and capillary rarefaction, and chronically leads to increased systemic vascular resistance. More recent findings suggest that sodium also acts as an important second messenger regulating energy metabolism and cellular functions. Besides endothelial cells and fibroblasts, sodium also affects innate and adaptive immunometabolism, immune cell function, and influences certain microbes and microbiota-derived metabolites. We propose the idea that the definition of salt sensitivity should be expanded beyond high blood pressure to cellular and molecular salt sensitivity.
Topics: Humans; Sodium; Sodium Chloride, Dietary; Endothelial Cells; Hypertension; Sodium Chloride; Blood Pressure
PubMed: 37675565
DOI: 10.1161/HYPERTENSIONAHA.123.19489 -
Nutrients Jun 2023The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with... (Review)
Review
The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases.
Topics: Humans; Endothelium, Vascular; Sodium; Cardiovascular Diseases; Endothelial Cells; Glycocalyx; Vascular Diseases; Sodium Chloride
PubMed: 37447199
DOI: 10.3390/nu15132873 -
Hypertension (Dallas, Tex. : 1979) Mar 2024Salt (sodium chloride) is an essential nutrient required to maintain physiological functions. However, for most people, daily salt intake far exceeds their physiological... (Review)
Review
Salt (sodium chloride) is an essential nutrient required to maintain physiological functions. However, for most people, daily salt intake far exceeds their physiological need and is habitually greater than recommended upper thresholds. Excess salt intake leads to elevation in blood pressure which drives cardiovascular morbidity and mortality. Indeed, excessive salt intake is estimated to be responsible for ≈5 million deaths per year globally. For approximately one-third of otherwise healthy individuals (and >50% of those with hypertension), the effect of salt intake on blood pressure elevation is exaggerated; such people are categorized as salt sensitive and salt sensitivity of blood pressure is considered an independent risk factor for cardiovascular disease and death. The prevalence of salt sensitivity is higher in women than in men and, in both, increases with age. This narrative review considers the foundational concepts of salt sensitivity and the underlying effector systems that cause salt sensitivity. We also consider recent updates in preclinical and clinical research that are revealing new modifying factors that determine the blood pressure response to high salt intake.
Topics: Male; Humans; Female; Sodium Chloride, Dietary; Sodium Chloride; Hypertension; Cardiovascular Diseases; Blood Pressure
PubMed: 37721034
DOI: 10.1161/HYPERTENSIONAHA.123.17959 -
Nutrients Aug 2023Sodium, contained in dietary salt, is essential to human life [...].
Sodium, contained in dietary salt, is essential to human life [...].
Topics: Humans; Sodium, Dietary; Sodium Chloride, Dietary
PubMed: 37686728
DOI: 10.3390/nu15173696