Abstract P050: Reproducibility of Blood Pressure Responses to Dietary Sodium and Potassium Interventions: the GenSalt Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Jiang He ◽  
Dongfeng Gu ◽  
Jichun Chen ◽  
Qi Zhao ◽  
Lydia A Bazzano ◽  
...  

Blood pressure (BP) responses to dietary sodium and potassium interventions vary among individuals (salt- and potassium-sensitivity). However, it is unknown whether salt- and/or potassium-sensitivity is a reproducible trait. We repeated the dietary sodium and potassium intervention among 488 Han Chinese who participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) four years after the original dietary intervention. The same dietary intervention protocol, which included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day), was applied in both the original and repeated studies. Three BP measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. Three timed urinary samples were collected to measure sodium and potassium excretion at baseline and during each intervention phase. On average, study participants were 39.7 years old and 49.4% of them were male. Study participants had a mean body mass index of 23.7 kg/m 2 , systolic BP of 118.1 mmHg, diastolic BP of 74.4 mmHg, urinary excretion of sodium of 258.8 mmol/24-hrs, and urinary excretion of potassium of 38.8 mmol/24-hrs. The results from the 24-h urinary excretions of sodium and potassium showed excellent compliance with the study diet. BP responses to dietary intervention in the original and repeated studies were highly correlated. For example, the correlation coefficients for systolic BP between original and repeated studies were 0.7681 at baseline, 0.7902 during low-sodium, 0.8045 during high-sodium, and 0.8232 during high-sodium and potassium supplementation intervention (all p<0.0001). The correlation coefficients for systolic BP changes between original and repeated studies were 0.3659 from baseline to low-sodium, 0.3655 from low to high-sodium, and 0.2850 from high-sodium to potassium supplementation (all p<0.0001). These data indicate that BP responses to dietary sodium and potassium intervention are reproducible traits. Furthermore, our study suggests that identification of individuals who are more sensitive to dietary sodium and potassium intake may improve the efficiency of targeted dietary intervention for hypertension prevention among high-risk individuals.

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Jiang He ◽  
Dongfeng Gu ◽  
Jing Chen ◽  
Jichun Chen ◽  
Qi Zhao ◽  
...  

It is well known that blood pressure (BP) responses to dietary sodium and potassium intakes vary among individuals (salt- and potassium-sensitivity). However, it is unknown whether salt- and/or potassium-sensitivity predict the risk of hypertension. We conducted a dietary sodium and potassium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day). Three BP measurements were obtained on each of the last 3 days of each intervention period at the baseline and each of the 3 days of follow-up examinations. Systolic BP responses (mean ± SD) to dietary intervention were -5.5±7.0 for low-sodium, 4.9±6.0 for high-sodium, and -3.5±5.5 for potassium-supplementation. Over an average of 7.4 years of follow-up, we identified 455 incidence hypertension cases (systolic BP≥140 mmHg and/or diastolic BP ≥90 mmHg and/or use of antihypertensive medication). The age-adjusted cumulative incidences of hypertension by the quartiles of systolic BP responses to dietary intervention were showed in the following table. These associations remained after adjustment for multiple covariates. These data indicate that BP responses to dietary sodium and potassium intervention are related to the subsequent risk of hypertension. Furthermore, our study suggests that individuals who are more sensitive to dietary sodium and potassium intake are at an increased risk for hypertension and should be target for dietary intervention.


2018 ◽  
Vol 31 (5) ◽  
pp. 582-589 ◽  
Author(s):  
Xiaolong Xing ◽  
Fangchao Liu ◽  
Xueli Yang ◽  
Chen Huang ◽  
Dingding Zhang ◽  
...  

Abstract BACKGROUND To explore how central hemodynamics respond to dietary sodium and potassium interventions, and whether the responses are associated with metabolic traits. METHODS We conducted a dietary intervention study including a 7-day low-sodium (51.3 mmol sodium/day) intervention, a 7-day high-sodium (307.8 mmol sodium/day) intervention, and a 7-day high-sodium with potassium supplementation (60.0 mmol potassium/day) intervention among 99 northern Chinese subjects aged 18–60 years. Five metabolic traits included abdominal obesity, high triglycerides, low HDL cholesterol, raised blood pressure (BP), and high glucose. Central hemodynamics were measured at baseline and during each intervention. RESULTS Central systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and augmentation index (AIx@75) significantly decreased during low-sodium intervention, increased during high-sodium intervention, and then decreased during potassium supplementation. We observed potential linear trends toward significance of central SBP and PP responses to low-sodium intervention, and significant linear trends of responses to high-sodium intervention as the number of metabolic traits grows. For example, among participants with 0 or 1, 2 or 3, and 4 or 5 metabolic traits, central SBP responses to high-sodium intervention were 8.8 [95% confidence interval (5.8, 11.8)], 9.3 (7.1, 11.6), and 14.0 (11.6, 16.3) mmHg, respectively (P for trend = 0.009). Significant linear trends of central SBP and DBP responses to potassium supplementation were also observed. CONCLUSIONS Central BP and AIx@75 were lowered by sodium reduction and potassium supplementation, and elevated by sodium-loading. The responses of central BP were pronounced among individuals with metabolic traits clustering. CLINICAL TRIALS REGISTRATION Trial Number NCT00721721 (The current study is registered on ClinicalTrials.gov; https://clinicaltrials.gov).


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Dongfeng Gu ◽  
Qi Zhao ◽  
Tanika N Kelly ◽  
James E Hixson ◽  
Dabeeru C Rao ◽  
...  

The kallikrein-kinin system (KKS) has been implicated in the pathogenesis of salt-sensitive hypertension in animal models. We comprehensively examined the association between genetic variants of the KKS and blood pressure (BP) response to dietary sodium intervention among participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study. A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was carried out among 1,906 GenSalt participants from rural areas of north China. Nine BP measurements were obtained at baseline and on the last three days of each intervention period using a random-zero sphygmomanometer. The percentage changes in mean BP from baseline to low-sodium intervention and from low-sodium to high-sodium intervention were used to assess individual salt-sensitivity. A total of 205 tagSNPs and functional SNPs of eleven genes of the KKS ( BDKRB1 , BDKRB2 , CPN1 , CPN2 , CPM , ECE1 , KLK1 , KLKB1 , KNG1 , MME , SERPINA4 ) were selected and genotyped in this study. Single marker analyses were conducted using the Family Based Association Test program. Genetic variants in the bradykinin receptor B2 ( BDKRB2 ) and endothelin converting enzyme 1 ( ECE1 ) genes showed significant associations with salt sensitivity even after adjusting for multiple testing using the false discovery rate method. SNP rs11847625 of BDKRB2 was significantly associated with systolic BP (SBP) response to low-sodium intervention ( P = 0.0001). Compared to its major allele G, carriers of the minor allele C had greater SBP decrease during low-sodium intervention. Furthermore, a haplotype containing allele C was associated with greater SBP increase to high-sodium intervention ( P = 0.0009). Seven SNPs of ECE1 , one of the degrading enzymes of kinins, were significantly associated with diastolic BP (DBP) response to low-sodium intervention ( P values ranged from 0.0003 to 0.002). Two haplotypes in the linkage disequilibrium block including these seven SNPs were significantly associated with DBP response to low-sodium intervention (P=0.0004 and 0.003, respectively). Our study found that the genetic variants of the KKS were associated with salt sensitivity of BP. Replication and functional studies of the identified variants are warranted in the future.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Lieke Gijsbers ◽  
James Dower ◽  
Marco Mensink ◽  
Johanna M Geleijnse

Introduction: We performed a 12-week randomized placebo-controlled crossover study to examine the effects of sodium and potassium supplementation on blood pressure (BP) and arterial stiffness in untreated (pre)hypertensive individuals on a low-sodium, low-potassium diet. Methods: During the study, subjects were on a fully controlled diet that provided on average 2.4 g/d of sodium (equals 6 g/d of salt) and 2.2 g/d of potassium. After a 1-week run-in period, 37 subjects received capsules with supplemental sodium (3 g/d, equals 7.5 g/d of salt), supplemental potassium (3 g/d), or placebo, for four weeks each (not separated by wash-out), in random order. Fasting office BP, 24-h ambulatory BP, and measures of arterial stiffness (SphygmoCor®) were assessed at baseline and after each treatment. Results: Subjects had a mean pre-treatment BP of 145/81 mmHg and 68% (25 of 37) had systolic BP (SBP) ≥140 mmHg. In 36 subjects who completed the study, sodium supplementation increased urinary sodium by 97.6 mmol/24h (2.2 g/d) and potassium supplementation increased urinary potassium by 62.9 mmol/24h (2.5 g/d), compared to placebo (Table). Sodium supplementation significantly increased office BP by 7.5/3.3 mmHg, 24-h BP by 7.0/2.1 mmHg and central BP by 8.5/3.6 mmHg. Potassium supplementation significantly reduced 24-h BP by 4.0/1.7 mmHg. Measures of arterial stiffness did not change. Conclusion: Increasing the intake of sodium has a strong adverse effect on BP in untreated (pre)hypertensive individuals. Increased potassium intake, however, lowers BP even when people are on a reduced sodium diet. Short-term changes in sodium and potassium intake have little effect on arterial stiffness. Trial registration: ClinicalTrials.gov Identifier: NCT01575041


1991 ◽  
Vol 69 (4) ◽  
pp. 507-511 ◽  
Author(s):  
John C. Passmore ◽  
Agnes E. Jimenez

The effect of selective dietary sodium and (or) chloride loading on blood pressure and renal blood flow (RBF) in the rat angiotensin II (AII) model of hypertension was determined. AII (200 ng/min) or saline was infused intraperitoneally. Diets were provided with either high or low concentrations of sodium, chloride or both ions for 22 days. The blood pressure of saline-treated animals was not increased by the high sodium chloride diet. Animals on a high sodium, high chloride diet had a significantly greater increase of blood pressure at 8, 15, 18, and 22 days of AII infusion compared with AII-treated animals on a low sodium, low chloride diet (p < 0.05). Selective dietary loading of either high sodium or chloride in AII-treated rats produced no greater elevation of blood pressure than AII with the low sodium, low chloride diet. Selective high dietary chloride was associated with a lower RBF in AII- and vehicle-treated rats compared with low dietary chloride. The chloride effect on RBF was greater in AII-treated animals. In conclusion, both sodium and chloride are necessary to produce the maximum increase of blood pressure in AII animals. AII enhances the decreased RBF induced by dietary chloride.Key words: angiotensin II, sodium chloride, blood pressure.


BMJ ◽  
2019 ◽  
pp. l772 ◽  
Author(s):  
Martin O’Donnell ◽  
Andrew Mente ◽  
Sumathy Rangarajan ◽  
Matthew J McQueen ◽  
Neil O’Leary ◽  
...  

AbstractObjectiveTo evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.DesignInternational prospective cohort study.Setting18 high, middle, and low income countries, sampled from urban and rural communities.Participants103 570 people who provided morning fasting urine samples.Main outcome measuresAssociation of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).ResultsMean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).ConclusionsThese findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Casey M Rebholz ◽  
Jing Chen ◽  
Qi Zhao ◽  
Dongfeng Gu ◽  
Jichun Chen ◽  
...  

Urine excretion of angiotensinogen (AGT) has been proposed as a biomarker of intrarenal renin-angiotensin system activity, and therefore as a proxy for blood pressure regulation and sodium homeostasis. The association between urine levels of AGT and blood pressure response to dietary sodium intake has not been previously examined in the general population. We assessed the hypothesis that there is a direct relationship between urine levels of AGT and salt-sensitivity of blood pressure among participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) replication study. A 7-day low-sodium intervention, followed by a 7-day high-sodium intervention was carried out among 698 GenSalt-replication study participants from rural areas of north China. Absolute urine AGT excretion (μg/24 hours) and AGT-to-creatinine ratio (AGT/Cr, μg/g) were estimated at baseline for a random sample of 100 study participants. Nine blood pressure measurements were obtained at baseline and on the last three days of each intervention period. The absolute and percent changes in mean blood pressure from low-sodium to high-sodium intervention were used to assess salt-sensitivity. Median AGT and AGT/Cr were significantly (both p=0.01) reduced during the low-sodium intervention (AGT: 7.16 μg/24 hours, AGT/Cr: 8.36 μg/g) and increased during the high-sodium intervention (AGT: 8.84 μg/24 hours, AGT/Cr: 10.92 μg/g) compared to baseline (AGT: 8.28 μg/24 hours, AGT/Cr: 9.40 μg/g). Log-transformed AGT and AGT/Cr ratio at baseline was significantly and positively associated with blood pressure at baseline and at the end of each intervention. For example, one standard deviation higher log-transformed AGT/Cr ratio (1.2 μg/g) was associated with a 4.0 mm Hg (95% confidence interval: 1.3, 6.7) higher systolic blood pressure level at the end of the high-sodium intervention (p=0.004). One standard deviation higher log-transformed AGT/Cr ratio was associated with 1.58-times increased odds of high salt-sensitivity (≥5% change) of blood pressure (95% confidence interval: 1.00, 2.50; p=0.049). Log-transformed AGT/Cr ratio at baseline was positively associated with absolute and percent systolic blood pressure change from low- to high-sodium interventions (absolute: r=0.23, p=0.02; percent: r=0.20, p=0.047). In conclusion, elevated levels of urine AGT are associated with sodium-sensitivity of blood pressure. Augmentation of renal-angiotensin system activity may play an important role in the development of salt-sensitive hypertension.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
X Xing ◽  
F Liu ◽  
X Yang ◽  
J Huang

Abstract Background Attenuated nighttime blood pressure (BP) fall during a high-sodium diet is associated with higher sodium sensitivity of BP. However, the prognostic value for sodium sensitivity of nighttime BP profile during a habitual diet is not fully understood. Purpose To elucidate the usefulness of nighttime BP and dipping patterns under a habitual diet in assessing sodium sensitivity. Methods We conducted a dietary intervention study among 250 resident aged 18–60 years with high-normal or stage I hypertension in rural areas of northern China. The 24-hour ambulatory BP monitoring and baseline survey were performed for each participant under a habitual diet during the first 3 days. Then participants underwent a 7-day low-sodium intervention (51.3mmol sodium per day), followed by a 7-day high-sodium intervention (307.8mmol sodium per day). Three clinic BP measurements were obtained in every morning of the 3-day baseline observation and days 5, 6, and 7 of each intervention period. Results Among 250 participants, 86 (34.4%) had daytime hypertension (DH) and 149 (59.6%) had nighttime hypertension (NH). The systolic BP (SBP) responses to low-sodium and high-sodium intervention were significantly higher in those with NH than those without irrespective of DH status [−8.1 (−9.3, −7.0) vs. −5.5 (−7.0, −4.1) mmHg, P=0.001; and 13.0 (11.6, 14.3) vs. 11.0 (9.3, 12.7) mmHg, P=0.038, respectively]. Compared with dippers, extreme dippers had significantly higher SBP responses to low-sodium and high sodium intervention independently of 24-hour SBP. Moreover, the quadratic curve between nighttime SBP fall and SBP responses to low-sodium (β=−105.5 for quadratic term, P=0.015) and high-sodium (β=108.9 for quadratic term, P=0.035) intervention suggested both non-dipping and extreme dipping might indicate higher sodium sensitivity. Conclusions NH as well as non-dipping and extreme dipping determined during a habitual diet might indicate higher sodium sensitivity, which highlights the potential usefulness of nighttime BP profile in assessing sodium sensitivity. Acknowledgement/Funding This study is supported by the National Natural Science Foundation of China (grant no. 81570386)


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jiang He ◽  
Jing Chen ◽  
Jianfeng Huang ◽  
Jichun Chen ◽  
Hua He ◽  
...  

It is well known that blood pressure (BP) responses to dietary sodium intake vary among individuals (salt-sensitivity and salt-resistance). However, it is unknown whether salt-sensitivity and salt-resistance predict the risk of hypertension. We conducted a dietary sodium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low-sodium feeding (51.3 mmol/day) and a 7-day high-sodium feeding (307.8 mmol/day). Three BP measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. We used latent class models to identify subgroups that share a similar underlying trajectory in BP responses to sodium intervention. Over an average of 7.4 years of follow-up, we identified 514 incident hypertension cases. The mean (standard deviation) change in systolic BP during low-sodium and high-sodium interventions according to salt-sensitive and -resistant groups are shown in the following table. In addition, age, sex, and baseline BP-adjusted and multiple-adjusted odds ratios (95% CI) of incident hypertension are shown in the following table. These data indicate that high responses or non-responses to dietary sodium intervention are related to the risk of hypertension. Furthermore, this is the first prospective cohort study to indicate that individuals with either salt-sensitivity or salt-resistance are at an increased risk for hypertension and should be targeted for dietary intervention.


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