The effect of uric acid and urinary sodium excretion on prehypertension: a nationwide population-based study.

BACKGROUND: This study examined the effect of serum uric acid (SUA) level and urinary sodium excretion on blood pressure as well as their combined effect on prehypertension in a Korean population. METHOD: Data from the 7th Korea National Health and Nutrition Examination Survey for adults (≥ 19 years of age) were used. The participants were classified into two groups, normotension and prehypertension, according to the JNC-7 definition. Logistic regression was carried out and adjusted for traditionally regarded confounders of blood pressure. All analyses considered a complex sampling design. A multivariate analysis was performed on subgroups defined according to their SUA level and urinary sodium excretion. RESULTS: The 4200 participants were divided into normotension (n = 2646) and prehypertension (n = 1554) groups. In the univariate analysis, patient age, male sex, concurrent comorbidity (diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and chronic kidney disease), uric acid, and urinary sodium excretion were associated with prehypertension. After adjusting for baseline covariates, both the SUA level and urinary sodium excretion were significant predictors of incident prehypertension (SUA, per 1 mg/dL increase, odds ratio [OR] 1.216, 95% confidence interval [95% CI] 1.131-1.309; urinary sodium excretion, per 1 g/day increase, OR 1.067, 95% CI 1.019-1.117). Additionally, simultaneously higher tertiles of SUA and urinary sodium excretion resulted in higher ORs for prehypertension. CONCLUSION: Increased SUA is a significant risk marker for the development of prehypertension in normotensives. Simultaneously high SUA and urinary sodium excretion amplified the effect on the development of prehypertension. Our findings suggest that lowering SUA levels and reducing sodium intake will contribute to preventing hypertension.

Trend of salt intake measured by 24-hour urine collection samples among Iranian adults population between 1998 and 2013: The Isfahan salt study.

BACKGROUND AND AIM: Few population-based studies conducted in the Eastern Mediterranean region assessed salt intake by the measurement of 24-h sodium urine excretion (24-hUNa). The current study aimed to assess the trend of mean salt intake in Iranian adults between 1998 and 2013. METHODS AND RESULTS: These cross-sectional studies were performed on 564, 157, 509 and 837 randomly selected healthy adults aged >18 years from Isfahan city, Iran, in 1998, 2001, 2007 and 2013, respectively. BP was measured using a mercury sphygmomanometer according to a standard protocol. Single 24-h urine was collected to assess 24-hUNa as a surrogate of salt intake, and 24-h urinary K (24-hUK). The estimated trend of salt intake was 9.5, 9.7, 9.6 and 10.2 g/day in total population (P < 0.001). The increase in salt intake between 1998 and 2013 was significant only in men, (P < 0.001). The risk of pre-hypertension was 21% and 18% significantly greater in the highest quartiles of UNa/UK after adjustment for potential confounders in 2001 and 2013, respectively, [OR (95% CI): 1.21 (1.03-1.64) and 1.18 (1.02-1.38), respectively]. CONCLUSIONS: This population-based study indicated that mean salt intake was about two times of recommendation in Isfahan city, Iran, and suggest that it would be essential to implement a salt reduction strategy program in Iranian population. Longitudinal national studies with larger samples examining the trend of salt intake are warranted.

Activity of lysosomal exoglycosidases in the urine of healthy normotensive and pre-hypertensive children.

PURPOSE: We investigated the relationship between blood pressure (BP) and the activity of lysosomal exoglycosidases: N-acetyl-ß-hexosaminidase (HEX), its isoenzymes A (HEX A) and B (HEX B), α-fucosidase (FUC), ß-galactosidase (GAL), ß-glucuronidase (GLU) and α-mannosidase (MAN) in pre-hypertensive (high normal blood pressure - HNBP) and normal blood pressure (NBP) children. MATERIAL AND METHODS: The study was carried out with urine samples collected from 176 children, aged 6-17.9 years, divided into 2 groups: 42 HNBP and 134 NBP subjects. The children were stratified depending on systolic and diastolic BP (SBP; DBP): HNBP (SBP and/or DBP greater than or equal to the 90th percentile, but less than the 95th percentile) for sex, age, and height; and NBP (SBP and DBP less than the 90th centile). The activities of lysosomal exoglycosidases were determined by the colorimetric method, and expressed in pKat/mL and pKat/µgCr. RESULTS: The activity of urinary HEX A in HNBP group was significantly higher than in NBP (p < 0.05). The HNBP group showed significant positive correlation between HEX, HEX A (pKat/mL) and SBP. AUC for HEX A was 0.616, cut-off value -29.351 pKat/mL (sensitivity 51.2%, specificity 71.8%), and 0.589, cut-off value -0.054 pKat/µgCr (sensitivity 31.7%, specificity 86.3%). CONCLUSIONS: This is the first report of the relationship between BP and the activity of urinary lysosomal exoglycosidases: HEX, HEX A and HEX B, FUC, GAL, GLU, and MAN in healthy children and adolescents. It seems that HEX A (pKat/mL) can be used as a useful tool in identifying children with HNBP.

Association of sodium intake with insulin resistance in Korean children and adolescents: the Korea National Health and Nutrition Examination Survey 2010.

BACKGROUND: This study aimed to evaluate the relationship between sodium intake and insulin resistance indices. METHODS: A total of 718 Korean children and adolescents (411 boys) aged 10-18 years who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) were included in the study. The urinary sodium to urinary creatinine ratio was used as a surrogate for sodium intake. The homeostatic model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were used as indices of insulin resistance. RESULTS: The mean urinary sodium to urinary creatinine ratio was 11.34 in males and 10.17 in females. The urinary sodium to urinary creatinine ratio was significantly positively correlated with HOMA-IR (r=0.165, p<0.001) and inversely correlated with QUICKI (r=-0.181, p<0.001) in Pearson's correlation analyses. In a multivariate linear regression analysis, the urinary sodium to urinary creatinine ratio was independently and significantly positively associated with HOMA-IR (ß=0.073, p=0.018) and significantly inversely associated with QUICKI (ß=-0.080, p=0.007) after adjustment for possible confounders. HOMA-IR was independently and significantly positively associated with the urinary sodium to urinary creatinine ratio (ß=0.087, p=0.018), whereas QUICKI was independently and significantly negatively associated with the urinary sodium to urinary creatinine ratio (ß=-0.097, p=0.009) after controlling for confounders. CONCLUSIONS: Our results suggest that sodium intake, as estimated by the urinary sodium to urinary creatinine ratio, may be independently associated with insulin resistance in children and adolescents.

Urinary sodium excretion and dietary sources of sodium intake in Chinese postmenopausal women with prehypertension.

BACKGROUND: Reducing salt intake in communities is one of the most effective and affordable public health strategies to prevent hypertension, stroke and renal disease. The present study aimed to determine the sodium intake in Hong Kong Chinese postmenopausal women and identify the major food sources contributing to sodium intake and urine excretion. METHODS: This was a cross-sectional study among 655 Chinese postmenopausal women with prehypertension who were screened for a randomized controlled trial. Data collection included 24 h urine collection for the measurement of sodium, potassium and creatinine, 3-day dietary records, anthropometric measures and questionnaire survey on demographic data and dietary habits. RESULTS: The average salt intake estimated from urinary excretion was 7.8 ± 3.2 g/d with 82.1% women above WHO recommendation of 5 g/day. Food groups as soup (21.6%), rice and noodles (13.5%), baked cereals (12.3%), salted/preserved foods (10.8%), Chinese dim sum (10.2%) and sea foods (10.1%) were the major contributors of non-discretionary salt. Discretionary salt use in cooking made a modest contribution to overall intake. Vegetable and fruit intake, age, sodium intake from salted foods, sea foods and soup were the independent determinants of urinary sodium excretion. CONCLUSIONS: Our data revealed a significant room for reduction of the sodium intake. Efforts to reduce sodium from diets in Hong Kong Chinese postmenopausal women should focus on both processed foods and discretionary salt during cooking. Sodium reduction in soup and increase in fruit intake would be potentially effective strategy for reducing sodium.

Association of a reduction in central obesity and phosphorus intake with changes in urinary albumin excretion: the PREMIER study.

BACKGROUND: Excess adiposity and dietary factors may be important determinants of urinary albumin excretion (UAE). STUDY DESIGN: Observational analysis of PREMIER, a randomized trial designed to lower blood pressure using behavioral interventions (counseling on weight loss, healthy diet, and exercise). SETTING & PARTICIPANTS: 481 participants with normal kidney function who provided adequate 24-hour urine collections at baseline and 6 months. PREDICTORS: Change in waist circumference; 24-hour urine sodium, potassium, and phosphorus excretion; and protein intake estimated from urea nitrogen. OUTCOMES & MEASUREMENTS: The primary outcome was change in log-transformed 24-hour UAE over 6 months. RESULTS: After 6 months, the proportion of individuals with UAE ≥10 mg/d decreased from 18.7% to 12.7% (P < 0.001). Changes in mean waist circumference (-4.2 ± 6.6 [SD] cm), 24-hour excretion of sodium (-28.2 ± 71.7 mmol/d), potassium (+8.4 ± 27.8 mmol/d), phosphorus (-27.7 ± 314.1 mg/d), and protein intake (-1.7 ± 19.4 g/d) were observed. After adjustment for relevant covariates, the following variables were associated significantly with reduction in ln(UAE) in separate models: decrease in waist circumference (P = 0.001), decrease in 24-hour urine phosphorus excretion (P < 0.001), and decrease in protein intake (P = 0.01). In a multivariable model including these 3 predictors, decreases in waist circumference (P = 0.002) and 24-hour urine phosphorus excretion (P = 0.03), but not change in protein intake (P = 0.5), remained associated significantly with reduction in ln(UAE). These associations remained significant even after adjustment for changes in blood pressure and insulin resistance. Baseline UAE and metabolic syndrome modified the relationship of waist circumference with ln(UAE); specifically, individuals with higher UAE and baseline metabolic syndrome experienced greater reductions in ln(UAE) from decreases in waist circumference. LIMITATIONS: Observational study with potential for confounding. CONCLUSIONS: In adults with normal kidney function, decreases in waist circumference and 24-hour urine phosphorus excretion are associated with reductions in UAE. These findings support the rationale for clinical trials to determine whether reducing dietary phosphorus intake or waist circumference could prevent chronic kidney disease or slow its progression.

Urinary phthalates are associated with higher blood pressure in childhood.

OBJECTIVE: To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children. STUDY DESIGN: We performed a cross-sectional analysis of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates--low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)--based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels. RESULTS: Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z-score was identified (P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension. CONCLUSIONS: Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention.

Is the association between salt intake and blood pressure mediated by body mass index and central adiposity?

OBJECTIVE: To assess the amount of salt intake among normotensive (NT) and prehypertensive (PHT) subjects and to determine whether the association between salt intake and blood pressure is correlated with body weight and waist circumference (WC) or is independent. METHODS: A total of 806 NT and PHT subjects from Isfahan Healthy Heart Program (IHHP) were enrolled in the study. A standard questionnaire was used to assess sociodemographic characteristics. The amount of salt intake was measured by the 24-hour urine collection method. Blood pressure, height, weight, and WC were measured based on standard protocols. RESULTS: The mean ages (± SD) of NT and PHT subjects were 35.9 (± 11.9) and 44.7 (± 12.5) years, respectively (P < 0.001). The mean values of body mass index (BMI) and WC were greater among PHT than NT subjects (BMI: 27.9 ± 3.8 vs. 25.1 ± 4.3 kg/m2; P < 0.001 and WC: 90.2 ± 8.6 vs. 81.2 ± 11.2 cm; P < 0.001, respectively). PHT subjects had higher amount of salt intake than NT ones (10.3 ± 6.2 vs. 12.7 ± 7.1 g/d, respectively; P = 0.003). Odds ratio (OR) for being PHT increased significantly across the tertiles of salt intake in crude model and sociodemographic- adjusted model. Further adjustment for BMI and WC values weakened the OR for being PHT and showed nonsignificant trend (OR (and 95% CI) for BMI across tertiles of salt intake: 1, 1.26 (0.59 - 2.69), 1.89 (0.93 - 3.81); P = 0.063 and OR (and 95% CI) for WC across tertiles of salt intake: 1, 1.22 (0.58 - 2.57), 1.79(0.89 - 3.56); P = 0.082). CONCLUSION: The findings of this study suggest that the association between salt intake and blood pressure is related to body weight and WC.

Relationship between inflammation and microalbuminuria in prehypertension.

Inflammation is a pathogenic factor for target-organ damage (TOD) in hypertension. This study examined the relationship between inflammatory parameters and urinary albumin excretion (UAE) in prehypertension. A total of 65 prehypertensive subjects (blood pressure (BP) 120-139/80-89 mm Hg) and 26 healthy volunteers with BP <120/80 mm Hg were included. High-sensitivity C-reactive protein (hs-CRP), and serum and urinary tumor necrosis factor-α (TNF-α) were measured as inflammatory markers. Prehypertensive individuals had higher levels of inflammatory parameters and UAE than healthy subjects. Analyses carried out in prehypertensive participants showed that BP was similar between individuals with normoalbuminuria or microalbuminuria (MAB) (UAE between 30 and 299 mg per day). However, serum hs-CRP and urinary TNF-α excretion were higher in prehypertensives with MAB. Multiple regression analysis showed that systolic blood pressure (r=0.29, P<0.01), hs-CRP (r=0.20, P<0.001), and urinary TNF-α (r=0.69, P<0.001) were independently correlated with UAE (adjusted R(2)=0.73, P<0.001). Finally, logistic regression analysis performed in the prehypertensive group with the absence or presence of MAB as the dependent variable demonstrated that hs-CRP (3.92 (1.45-10.58), P=0.007) and urinary TNF-α (1.69 (1.20-2.37), P=0.002) were independent risk factors for the presence of MAB. Inflammatory parameters are significantly and independently associated with UAE in prehypertensive subjects, suggesting that inflammation may be a pathogenic factor for the early vascular or TOD in these individuals.

[Association between urinary albumin-to-creatinine ratio and prehypertension].

OBJECTIVE: This study was operated to investigate the association between urinary albumin-to-creatinine ratio (UACR) and physical situations as hypertension and prehypertension among women. METHODS: Blood pressure, height, weight and waist circumference were measured and factors such as cigarette smoking, alcohol intake, family history of hypertension, were investigated. Blood glucose and lipid, serum uric acid, urinary albumin and urinary creatinine were tested on 1796 women aged ≥ 30 years living in the Jinchang district of Suzhou. Associations between UACR and hypertension as well as prehypertension were analyzed, by using ordinal multinomial logistic regression models. RESULTS: The mean levels of UACR were 15.54 (7.67, 32.53), 9.01 (5.45, 18.06), 7.13 (4.60, 12.50) mg/g and the rates of higher UACR were 27.57%, 13.42%, 9.61% in hypertensive, pre-hypertensive and normotensive subjects, respectively, with significant differences noticed among the three groups (P < 0.05). The average systolic blood pressure/diastolic blood pressure appeared to be 125.3/80.9, 128.8/82.7, 130.8/84.0 and 135.1/85.9 mm Hg for participants with UACR in the first, second, third and fourth quartile, respectively. The risks of prehypertension or hypertension increased with increasing UACR levels. Dose-response relationship was seen between UACR and risks of prehypertension or hypertension. Multivariable adjusted odds ratios (95%CI) of prehypertension or hypertension in the upper quartiles of UACR were 1.32 (1.02, 1.70), 1.72 (1.32, 2.24), and 2.37 (1.80, 3.11), respectively, when compared with the lowest quartile. CONCLUSION: Elevated UACR was associated with both hypertension and prehypertension among women.

Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects.

A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria, and further to vasoprotective NO endogenously. In the present study, two separate randomly controlled, single-blind, cross-over, postprandial studies were performed in normotensive volunteers. Ambulatory blood pressure (BP) was measured over a 24 h period following consumption of either four doses of beetroot juice (BJ), 0, 100, 250 and 500 g (n 18), or three bread products, control bread (0 g beetroot), red beetroot- and white beetroot-enriched breads (n 14). Total urinary nitrate/nitrite (NO(x)) was measured at baseline, and at 2, 4 and 24 h post-ingestion. BJ consumption significantly, and in a near dose-dependent manner, lowered systolic BP (SBP, P < 0·01) and diastolic BP (DBP, P < 0·001) over a period of 24 h, compared with water control. Furthermore, bread products enriched with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h (red beetroot-enriched bread, P <0·05), with no statistical differences between the varieties. Total urinary NO(x) significantly increased following the consumption of 100 g (P < 0·01), 250 g (P <0·001) and 500 g BJ (P <0·001) and after red beetroot-enriched bread ingestion (P <0·05), but did not reach significance for white beetroot-enriched bread compared with the no-beetroot condition. These studies demonstrated significant hypotensive effects of a low dose (100 g) of beetroot which was unaffected by processing or the presence of betacyanins. These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables.

Protein supplementation lowers blood pressure in overweight adults: effect of dietary proteins on blood pressure (PROPRES), a randomized trial.

BACKGROUND: Dietary protein intake may help to manage blood pressure (BP) and prevent complications associated with elevated BP. OBJECTIVE: The objective of this study was to determine whether 4 wk of increased protein intake (∼25% compared with ∼15% of energy intake that isoenergetically replaces carbohydrate intake) lowers office and daytime BP compared with increased carbohydrate intake. DESIGN: A randomized, double-blind, parallel study compared consumption of 3 × 20 g protein/d (20% pea, 20% soy, 30% egg, and 30% milk-protein isolate) with 3 × 20 g maltodextrin/d. Protein or maltodextrin were isoenergetically substituted for a sugar-sweetened drink. Primary outcomes were office and daytime BP. A total of 99 men and women [age range: 20-70 y; BMI (in kg/m²): 25-35] with untreated elevated BP (BP ≥130/85 and <160/100 mm Hg) were randomly assigned. Ninety-four completers (51 subjects in the maltodextrin group, 43 subjects in the protein group) were included in the analyses. RESULTS: Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 4.9 ± 1.7 mm Hg (P = 0.005) and 2.7 ± 1.3 mm Hg (P = 0.05) lower, respectively, in the protein group. Daytime SBP was 4.6 ± 1.7 mm Hg lower in the protein group (P = 0.006), whereas daytime DBP did not differ between groups (P = 0.37). Urinary sodium excretion was higher in the maltodextrin group (P = 0.004). CONCLUSION: Increased protein intake, at the expense of maltodextrin, lowers BP in overweight adults with upper-range prehypertension and grade 1 hypertension. This trial was registered at www.trialregister.nl as NTR 1362.

A comparison of the natriuretic and kaliuretic effects of cicletanine and hydrochlorothiazide in prehypertensive and hypertensive humans.

OBJECTIVES: The aim of this study was to compare the single-dose effects of thiazide-type diuretics cicletanine and hydrochlorothiazide (HCTZ), on natriuresis and kaliuresis in prehypertensive and treatment-naïve, stage 1 hypertensive patients and to explore the impact of GRK4 gene polymorphisms on thiazide-induced urinary electrolyte excretion. METHODS: The study was a randomized, double-blind, placebo-controlled, three-period, four-treatment, balanced incomplete block, cross-over study in male patients assigned to treatment sequences consisting of placebo, cicletanine 50 mg, cicletanine 150 mg, and HCTZ 25 mg, doses used to treat hypertension. Cumulative urine samples were collected predosing and over 24 h after dosing in each period to compare urine electrolyte excretion profiles of potassium (UKV), sodium (UNaV), magnesium, calcium, phosphate, chloride, and pH among groups. Each treatment was administered to 18 different patients in each period, and an equal number of patients had less than and at least three GRK4 allele variants. RESULTS: Compared with placebo, mean UKV was significantly increased with HCTZ 25 mg (12.7 mmol/day; P ≤ 0.001), cicletanine 50 mg (4.6 mmol/day; P = 0.026), and cicletanine 150 mg (5.5 mmol/day; P = 0.011), and mean UNaV was significantly increased with HCTZ 25 mg (102.2 mmol/day; P ≤ 0.001), cicletanine 50 mg (21.7 mmol/day; P = 0.005), and cicletanine 150 mg (57.9 mmol/day; P ≤ 0.001). CONCLUSION: All treatments had more natriuresis, diuresis, and kaliuresis than placebo, and both doses of cicletanine had less kaliuresis than HCTZ. These findings suggest that cicletanine is a favorable and well tolerated option for the treatment of hypertension with an improved safety profile compared with HCTZ.

Urinary albumin-to-creatinine ratio in a first-morning void urine and prehypertension among Chinese Han women.

BACKGROUND: This study was operated to investigate the association between urinary albumin-to-creatinine ratio (ACR) and prehypertension among Chinese Han women. METHODS: Information on blood pressure measurement and other variables were obtained, and blood and urine samples collected in 1796 women aged ≥30 years. The association between urinary ACR and prehypertension were analyzed by using multivariate non-conditional logistic regression models. RESULTS: Average urinary ACR was higher in hypertensives than in prehypertensives (median: 15.54 vs 9.01 mg/g), and in prehypertensives than in normotensives (median: 9.01 vs 7.13 mg/g). Both systolic and diastolic blood pressures increased with urinary ACR. Compared with the lowest quartile of urinary ACR, multivariate adjusted odds ratios of prehypertension were 1.25 (95% confidence interval, 0.89-1.78), 1.95 (1.30-2.92) and 1.59 (1.02-2.48) for the second, third and fourth quartiles, respectively. After exclusion of subjects with diabetes or use of antihypertensive medication, the odds ratio of prehypertension still increased with urinary ACR levels. CONCLUSION: Increased urinary ACR was significantly and positively associated with prehypertension among Chinese Han women.