Association between urinary sodium and potassium excretion and blood pressure and inflammation in patients with rheumatoid arthritis

Hypertension is highly prevalent in patients with rheumatoid arthritis (RA). In other populations, high sodium (Na⁺) and low potassium (K⁺) intake are associated with an increased risk of hypertension, and in animal models, a high salt intake exacerbated arthritis. Patients with RA have many comorbidities associated with salt sensitivity, but their salt intake and its relationship to blood pressure and inflammation is unknown. Using the Kawasaki formula, Na⁺ and K⁺ urinary excretion (reflecting intake) was estimated in 166 patients with RA and 92 controls, frequency matched for age, sex, and race. Inflammatory markers and disease activity were measured in RA patients. We tested the associations between blood pressure and Na⁺ and K⁺ excretion. Estimated 24-h Na⁺ excretion was similarly high in both RA (median [IQR] 5.1 g, [3.9–6.6 g]) and controls (4.9 g, [4.0–6.5 g]), p?=?0.9, despite higher rates of hypertension in RA (54 vs. 39%, p?=?0.03). The Na⁺:K⁺ excretion ratio was significantly higher in RA (2.0 [1.6–2.4]) vs. 1.7 [1.5–2.1]), p?=?0.02] compared to controls. In RA, a lower K⁺ excretion was inversely correlated with diastolic blood pressure (adjusted β?=???1.79, p?=?0.04). There was no significant association between Na⁺ or K⁺ excretion and inflammatory markers. Despite a similar Na⁺ excretion, patients with RA had higher rates of hypertension than controls, a finding compatible with increased salt sensitivity. Patients with RA had a lower Na⁺:K⁺ excretion ratio than controls, and lower K⁺ excretion was associated with higher diastolic blood pressure in RA.     

Daily response of blood pressure to day-to-day variation of urinary sodium to potassium ratio.

The relationship between blood pressure and urinary sodium-to-potassium (Na/K) ratio was assessed in eight healthy men, none of whom used antihypertensive medications. Blood pressure and urinary sodium and potassium concentrations were measured for 11 to 33 days without any dietary restriction. For two of the eight subjects, the urinary Na/K ratio significantly correlated with systolic blood pressure (r=0.70 and 0.45, respectively), and in one of the two subjects, the urinary ratio also positively correlated with diastolic blood pressure (r=0.72). In the others, no relationship between the ratio and blood pressure was observed (r=-0.24 to 0.26). The results indicate that, in some individuals, the daily variation of urinary Na/K ratio is closely correlated with day-to-day changes in blood pressure level, and suggest that the urinary Na/K ratio is useful in the management of the daily sodium and potassium intake balance of hypertensive patients who need to restrict salt intake.     

A HMGCR polymorphism is associated with relations between blood pressure and urinary sodium and potassium ratio in the Epic-Norfolk Study

A polymorphism in the HMGCR gene (rs17238540) was related to a lower response to pravastatin treatment and we aimed to investigate whether an interaction is present for this polymorphism on blood pressure (BP) and salt intake. Cross-sectional urinary sodium and potassium concentration and the polymorphism were assessed in a large population study. Participants with the mutated allele (G) had significantly higher BP than homozygous TT. There were highly significant positive trends between BP and urinary sodium:potassium ratio across quartiles in men, with less effect in women, especially women carrying the mutated allele, G. Multivariate regression showed a significant positive association between BP and the urinary sodium: potassium ratio that differed in men and women according to genotype. In men carrying the G allele, the regression slopes for diastolic BP and systolic BP were higher than in men TT and the opposite was observed in women. Our results suggest that the SNP rs17238540 in the HMGCR is associated with the BP response to urinary sodium: potassium ratio, the magnitude of the association differing according to possession of the G allele.     

Association of urinary sodium/potassium ratio with structural and functional vascular changes in non‐diabetic hypertensive patients

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24‐hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non‐diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24‐hour urine sample collection, assessment of carotid‐femoral pulse wave velocity (cf‐PWV, Complior), central hemodynamic parameters (SphygmoCor), and post‐occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24‐hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C‐reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10‐0.34) vs 1.19 (0.96‐1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114‐130) vs 135(125‐147) mmHg, P = .002] and cf‐PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf‐PWV (r = .41, P < .001), and post‐occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = −.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf‐PWV with urinary Na/K ratio (R ² = 0.17, P < .001) and PORH CVC with CRP (R ² = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non‐diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.     

长期补钾补钙对盐敏感儿童血压及其尿钠代谢的影响

为观察长期适量补充钾盐及钙盐对盐敏感儿童血压及其尿钠代谢的影响。对为期２年的补钾补钙随机双盲安慰剂对照试验的２６１名儿童进行了盐敏感性测定。结果显示：盐敏感性儿童，补钾补钙组２年期血压增长值较安慰剂组低４．３／４．８ｍｍＨｇ（Ｐ＜０．０５），前者血压增长幅度较后者低３．６／７．０个百分点（Ｐ＜０．０５）；而盐不敏感儿童，补充组与安慰剂组间血压变化无显著性差异。盐敏感性儿童经补钾补钙后，夜８小时尿钠排泄量明显增加（Ｐ＜０．０１），且后者与其血压增长幅度呈负相关（ｒ＝－０．３９，Ｐ＜０．０１）。提示，适量增加钾和钙的摄入，通过与钠离子的相互复合作用，促进尿钠排泄，可降低盐敏感儿童血压的增长幅度。     

Relation of urinary urea to blood pressure: interaction with urinary sodium

A previous study reported that urinary markers of protein intake are inversely related to blood pressure via unknown mechanisms. In man and rats, protein intake affects renal function and increases renal sodium excretion. The present study investigates the relation between markers of protein intake and blood pressure and the possible role of sodium in this relation. Blood pressure status, overnight urinary urea as index of protein intake, urinary and plasma sodium, and other variables were measured in a population sample of 3705 men and women, aged 25-74 years, without high plasma creatinine. Urinary urea was inversely related to blood pressure and hypertension: in multivariate analyses, 6.5 mmol/h higher urinary urea (about one s.d. in men and women) was related to 4.25 mm Hg lower systolic blood pressure (95% confidence interval = 1.34-8.49), and to 0.65 lower risk of hypertension (95% CI 0.34-0.87). An interaction was found between overnight urinary sodium and the relation of urinary urea to blood pressure: the relation was significant only in persons with overnight urinary sodium above the median. Urinary urea was significantly and inversely also related to plasma sodium. Data confirm an inverse relation to blood pressure of protein intake as measured by urinary urea. The possibility of sodium-related mechanisms is supported by the interaction of urinary sodium with the relation and by the inverse association of urinary urea with plasma sodium. The hypothesis is made that high protein intake could counteract sodium-dependent blood pressure rise via stimulation of renal sodium excretion.     

Geographic effect on racial blood pressure differences in adolescents

Standardized blood pressure measurements were obtained in populations of high school students in Washington, D.C. and in Bourbon County, Kentucky, a rural community. In Washington, mean systolic blood pressure (SBP) and the prevalence of high systolic blood pressure were greater in blacks than whites (P < 0.003), and among blacks the height of the blood pressure was associated with socio-economic status. In Bourbon County, there were no racial blood pressure differences, and mean SBP of both white and black Kentucky adolescents were higher than those of black Washington adolescents (P < 0.03). These observations suggest that environmental factors, including geographic differences, contribute to racial blood pressure differences in adolescents.     

北京郊区女性血清钾及血清钠钾比与血压关系

目的探讨北京郊区女性血钾及血钠钾比（Na/K）与血压的相关性。方法入选2216名女性受试者,对血压、体质指数（BMI）、高血压家族史和饮食类型进行记录。使用离子选择电极法测定受试者血Na＋、K＋水平。采用偏相关分析和二分类Logistic回归模型,分析血压和影响因素的关系。结果受调查人群高血压和正常血压高值的发生率分别为37.0%和34.1%,人群血Na＋、K＋、Na/K分别为（140.1±2.2）mmol/L、（4.3±0.3）mmol/L和（32.6±2.4）。在校正年龄后,血K＋与收缩压（SBP）、舒张压（DBP）、脉压差（PP）和平均动脉压（MAP）呈显著负相关（P〈0.01）,血Na/K与SBP、DBP、PP和MAP呈显著正相关（P〈0.001）。在Logistic回归模型中分别加入血K＋和Na/K,在调整了高血压家族史、年龄、BMI、血糖、总胆固醇的影响后,血K＋、Na/K仍是高血压的独立影响因素（ORK：0.446,95%CI：0.325～0.611;ORNa/K：1.118,95%CI：1.073～1.165）。在校正年龄后,膳食中蔬菜和奶制品的摄入量与血K＋呈正相关（P〈0.05）。结论北京郊区女性血K＋和Na/K水平与血压独立相关,血K＋的水平受膳食中蔬菜和牛奶摄入量的影响。     

Sodium excretion and racial differences in ambulatory blood pressure patterns.

The influence of Na+ excretion and race on casual blood pressure and ambulatory blood pressure patterns was examined in a biracial sample of healthy, normotensive children and adolescents (10-18 years; n = 140). The slopes relating 24-hour urinary Na+ excretion to systolic blood pressure were different for both black and white subjects for casual blood pressure (p less than 0.001) and blood pressure during sleep (p less than 0.03). For casual blood pressure, the slope was significant for black subjects (beta = 0.17; p less than 0.001) but not for white subjects. For blood pressure during sleep, the slope was again significant for black subjects (beta = 0.08; p less than 0.01) but not for white subjects. Na+ excretion was also related to awake levels of systolic blood pressure for black subjects (beta = 0.08, r = 0.36; p less than 0.01), although the slopes for both black and white subjects were not significantly different. Further analyses indicated the results were not due to racial differences in 24-hour urinary K+ excretion. However, plasma renin activity was marginally related to Na+ excretion in white subjects (r = 0.22; p less than 0.06) but not black subjects, a finding that is consistent with previous studies. Na+ excretion was not associated with diastolic blood pressure or heart rate in either group under any condition. The results of this study support research that has demonstrated a stronger relation between Na+ handling and casual blood pressure in black subjects and extend these findings to blood pressure while the subject is both awake and asleep.     

Association of haptoglobin with sodium sensitivity and resistance of blood pressure

Sodium sensitivity and resistance of blood pressure were examined in 117 normotensive and 85 hypertensive subjects by means of a protocol using rapid extracellular fluid volume expansion with intravenously administered saline (2 L over 4 hours) followed by a day of low dietary sodium intake (10 mEq) and volume contraction induced by a diuretic (furosemide, 120 mg orally). Genetic markers were also examined. Both hypertensive and normotensive subjects with haptoglobin 1-1 phenotype were significantly more (p less than 0.05) likely to be sodium-sensitive than were those with 2-1 or 2-2 phenotypes, and subjects with 2-2 phenotypes were more apt to be sodium-resistant. A second population was examined in which both adults and children with haptoglobin 1-1 phenotype were found to have significantly (p less than 0.05) higher casual systolic and diastolic blood pressures. These two studies independently confirm a relationship between haptoglobin phenotypes and blood pressure and suggest an environmental factor (sodium) as well.     

Associations of urinary sodium and sodium to potassium ratio with hypertension prevalence and the risk of cardiovascular events in patients with prehypertension

The aim of this study was to investigate the effects of urinary sodium and sodium to potassium ratio on inflammatory cytokines, hypertension, and cardiovascular disease in patients with prehypertension. The authors observed 627 patients with prehypertension in the General Hospital of Shenyang Military Region. Rank correlation analysis revealed that interleukin 6 expression exhibited significant positive correlations with urinary sodium (R = .13) and sodium to potassium ratio (R = .13). The multivariate‐adjusted hazard ratio of 24‐hour urinary sodium was 1.01 (95% confidence interval, 1.00 – 1.01) for hypertension and 1.01 (95% confidence interval, 1.00 – 1.02) for cardiovascular disease, whereas the hazard ratio for 24‐hour urinary sodium to potassium ratio was 1.13 (95% confidence interval, 1.08 – 1.19) for hypertension and 1.10 (95% confidence interval, 1.04 – 1.17) for cardiovascular disease. The study suggests that a high‐salt diet may lead to increased interleukin 6 levels and may contribute to hypertension. In addition, a high sodium to potassium ratio and high sodium levels are associated with increased risks of cardiovascular disease and hypertension in patients with prehypertension.     

Race and sex differences in the correlates of blood pressure change

Potential predictors of systolic and diastolic blood pressure change between 1960 and 1967 in the biracial population of Evans County, Georgia, were investigated. An all possible regressions multiple linear regression analysis was used. For systolic blood pressure change, the level of systolic blood pressure, age, and change in Quetelet index were significant (p less than 0.05) correlates in white men. The level of systolic blood pressure, the level and change of socioeconomic status, change in Quetelet index, and change in cholesterol were significant correlates for white women. The level of Quetelet index was of borderline significance (p less than 0.055) when the other significant variables were included in the model for white women. The change in Quetelet index was the only significant correlate of systolic blood pressure change in blacks. For diastolic blood pressure change, age, change in hematocrit, and change in Quetelet index were significant correlates for white men. Age, level and change of socioeconomic status, level and change of Quetelet index, and change in hematocrit were the significant correlates in white women. In black men, change in Quetelet index and age were significant. In black women, only age was a significant correlate of diastolic blood pressure change. These results indicate that there may be important differences in these correlates between race-sex groups and thus in the mechanism of blood pressure change for different race-sex groups. groups.     

Discrepant acute effect of saline loading on blood pressure,urinary sodium and potassium according to salt intake level: EpiSS study

Acute dietary salt intake may cause an elevation in blood pressure (BP). The study aimed to assess the acute effect of saline loading on BP in subjects with different levels of salt intake. This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. The sodium excretion in the 24‐hour urine was calculated for estimating the level of salt intake. Subjects were performed an acute oral saline loading test (1 L), and data of 2019 participants were included for analyses. Multivariate linear regression and stratified analyses were performed to identify associations between 24‐hour urinary sodium (24hUNa) with BP changes. Due to saline loading, systolic BP (SBP), pulse pressure, and urinary sodium concentration were significantly increased, while diastolic BP, heart rate, and urinary potassium concentration were significantly decreased. The SBP increments were more significant in subjects with lower salt intake, normotensives, elders, males, smokers, and drinkers. There was a significant linear negative dose‐response association between SBP increment with 24hUNa (β = −0.901, 95% CI: −1.253, −0.548), especially in lower salt intake individuals (β = −1.297, 95% CI: −2.338, −0.205) and hypertensive patients (β = −1.502, 95% CI: −2.037, −0.967). After excluding patients who received antidiabetic or antihypertensive medicines, the effects of negative associations weakened but remained significantly. In conclusion, acute salt loading leads to an increment in SBP, and the increased SBP was negatively related with 24hUNa. This study indicated avoiding acute salt loading was important for escaping acute BP changes, especially in lower salt intake populations.     

Association of red blood cell sodium leak with blood pressure in recombinant inbred strains.

Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+) transport (susceptible or resistant to inhibition by loop diuretics) were determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)-sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with slightly decreased red blood cell Na+ content in SHR compared with BN rats. Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium, whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide-resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the disclosed ion transport alterations with blood pressure was examined in 20 recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net uptake) cosegregated with systolic and pulse pressures but not diastolic pressure of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+ efflux nor any component of ouabain-resistant Rb+ uptake correlated positively with blood pressure of the recombinant inbred strains. Increased ouabain-resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+ extrusion because red blood cell Na+ content was not elevated in the hypertensive strains. Thus, high cell Na+ turnover rates might be related to genetic hypertension if an altered Na+ inward leak would be less effectively compensated for in tissues involved in cardiovascular regulation.     

Patterns of sodium and potassium excretion and blood pressure in the African Diaspora

Habitual levels of dietary sodium and potassium are correlated with age-related increases in blood pressure (BP) and likely have a role in this phenomenon. Although extensive published evidence exists from randomized trials, relatively few large-scale community surveys with multiple 24-h urine collections have been reported. We obtained three 24-h samples from 2704 individuals from Nigeria, Jamaica and the United States to evaluate patterns of intake and within-person relationships with BP. The average (±s.d.) age and weight of the participants across all the three sites were 39.9±8.6 years and 76.1±21.2?kg, respectively, and 55% of the total participants were females. Sodium excretion increased across the East-West gradient (for example, 123.9±54.6, 134.1±48.8, 176.6±71.0 (±s.d.) mmol, Nigeria, Jamaica and US, respectively), whereas potassium was essentially unchanged (for example, 46.3±22.9, 40.7±16.1, 44.7±16.4 (±s.d.) mmol, respectively). In multivariate analyses both sodium (positively) and potassium (negatively) were strongly correlated with BP (P<0.001); quantitatively the association was stronger, and more consistent in each site individually, for potassium. The within-population day-to-day variation was also greater for sodium than for potassium. Among each population group, a significant correlation was observed between sodium and urine volume, supporting the prior finding of sodium as a determinant of fluid intake in free-living individuals. These data confirm the consistency with the possible role of dietary electrolytes as hypertension risk factors, reinforcing the relevance of potassium in these populations.     

自然人群血糖、体重指数、腰臀比与血压的关系

目的：探讨自然人群中血糖、体重指数（BMI）、腰臀比（WHR）的水平对血压的影响及作用的大小。方法：应用1998年广东省糖尿病流行病学调查资料，采用分层整群抽样方法，调查对象年龄在20-74岁。血糖值为早晨空腹口服75g葡萄糖2h后的血糖值。糖悄病及糖耐量低减（IGT）的诊断标准采用1999年WHO糖尿病诊断标准。高血压诊断标准采用1999年中国高血压防治指南。结果：共调查11377人，其中男性5183人，女性6194人，平均年龄43岁，平均收缩压、舒张压、血糖、体重指数、腰臀比分别为117mmHg、74mmHg、104mg/dL、22kg/m^2和0.84。糖尿病高血压患病率明显高于血糖正常，为45.3％比14.4％，糖耐量低减高血压患病率明显高于糖耐量正常，为32.2％比14.5％，肥胖高血压患病率明显高于非肥胖，为21.5％比10.4％。多重线性回归模型分析显示，年龄、血糖体重指数、腰臀比对男女性收缩压和舒张压有显影响。结论：广东省自然人群的分析结果显示，血糖、体重指数和腰臀比是影响血压的重要因素，在控制我省高血压患病率不断增加的同时，尚须要注意控制血糖、体重指数和腰臀比的升高。     

Trends in blood pressure and urinary sodium and potassium excretion in Japan: reinvestigation in the 8th year after the Intersalt Study

Using the identical protocol of an Intersalt Study previously conducted, we undertook a new study (Intersalt-2) 8 years later. We measured changes in various factors affecting blood pressure (BP) including urinary sodium and potassium excretion in three districts of Japan: Osaka, Tochigi, and Toyama. Also we evaluated the trends in the relationships of those factors to BP. The Intersalt Study revealed that the average sodium excretion of all three study centres was high (particularly in Toyama) while potassium excretion was relatively low. The sodium/potassium ratio was therefore relatively high. The body mass index (BMI) was favourable, but the prevalence of heavy alcohol drinkers was high. Comparing the first to the second study reveals a decrease in sodium excretion in Toyama, although that area still had the highest value of the three study centres. The average potassium excretion increased only in Osaka. Sodium/potassium ratio decreased in all centres. BMI and the prevalence of heavy drinkers among the subjects of both studies were nearly the same. The trend of the relationship of sodium to BP in Osaka changed from negative to positive. In Toyama, it changed from positive to negative. It is thought that this negative relationship might occur in conjunction with a reduction in salt consumption in a population. In conclusion this study reveals that average sodium consumption in Japan remains high while potassium consumption is still low. As a factor in the prevention of hypertension, further efforts to reduce salt consumption and increase potassium intake are still needed.