Objective To investigate the impact of a high-salt diet on blood pressure level and the prevalence of hypertension in individuals with varying salt-sensitive phenotypes.Methods In 2004,339 participants from northern China were subjected to a chronic salt loading diet intervention study,and their salt-sensitive phenotypes were determined based on the study results.The participants were divided into salt-sensitive and salt-insensitive groups.In 2018,we randomly selected 152 participants for follow-up from the original cohort,and assessed their salt intake through 24-hour urine sodium level.The participants were divided into different groups based on various criteria to comprehensively investigate the effects of high-salt diet on blood pressure level and hypertension prevalence in individuals with different salt-sensitive phenotypes.Results Among the 339 subjects,154 were identified as salt-sensitive,accounting for 45.4％,while 185 were classified as salt-insensitive,accounting for 54.4％.The average arterial pressure response to high-salt intake after switching from low-salt intake in salt-sensitive individuals was 8.31(7.60,9.02),while the average arterial pressure response in salt-insensitive individuals was-1.09(-1.49,-0.68).A follow-up visit was conducted in 152 participants,It was found that the systolic blood pressure and diastolic blood pressure[divided according to the average daily salt intake(＞11 g).SBP:140.8 mmHg vs.132.9 mmHg,DBP:85.9 mmHg vs.81.6 mmHg,P＜0.05;divided according to the quartile of daily salt intake,SBP:140.8 mmHg vs.132.9 mmHg,DBP:85.9 mmHg vs.81.6 mmHg,P＜0.05]were significantly higher in the high-salt diet group than in the normal salt diet group in salt-sensitive individuals,but there was no significant difference in salt-insensitive individuals(P＞0.05).Additionally,the high-salt diet could significantly increase the incidence of hypertension among salt-sensitive individuals[divided according to the average daily salt intake(＞11 g):58.8％vs.32.8％,P＜0.05;divided according to the quartile of daily salt intake:58.8％vs.32.8％,P＜0.05],but had no effect on salt-insensitive individuals(P＞0.05).Conclusion A high-salt diet can increase systolic blood pressure and diastolic blood pressure in salt-sensitive individuals,and significantly increase the long-term prevalence of hypertension in salt-sensitive individuals,but not in salt-insensitive individuals.Therefore,the salt-sensitive phenotype plays a crucial role in the relationship between salt intake and salt-sensitive hypertension.

Objective To investigate the impact of a high-salt diet on blood pressure level and the prevalence of hypertension in individuals with varying salt-sensitive phenotypes.Methods In 2004,339 participants from northern China were subjected to a chronic salt loading diet intervention study,and their salt-sensitive phenotypes were determined based on the study results.The participants were divided into salt-sensitive and salt-insensitive groups.In 2018,we randomly selected 152 participants for follow-up from the original cohort,and assessed their salt intake through 24-hour urine sodium level.The participants were divided into different groups based on various criteria to comprehensively investigate the effects of high-salt diet on blood pressure level and hypertension prevalence in individuals with different salt-sensitive phenotypes.Results Among the 339 subjects,154 were identified as salt-sensitive,accounting for 45.4％,while 185 were classified as salt-insensitive,accounting for 54.4％.The average arterial pressure response to high-salt intake after switching from low-salt intake in salt-sensitive individuals was 8.31(7.60,9.02),while the average arterial pressure response in salt-insensitive individuals was-1.09(-1.49,-0.68).A follow-up visit was conducted in 152 participants,It was found that the systolic blood pressure and diastolic blood pressure[divided according to the average daily salt intake(＞11 g).SBP:140.8 mmHg vs.132.9 mmHg,DBP:85.9 mmHg vs.81.6 mmHg,P＜0.05;divided according to the quartile of daily salt intake,SBP:140.8 mmHg vs.132.9 mmHg,DBP:85.9 mmHg vs.81.6 mmHg,P＜0.05]were significantly higher in the high-salt diet group than in the normal salt diet group in salt-sensitive individuals,but there was no significant difference in salt-insensitive individuals(P＞0.05).Additionally,the high-salt diet could significantly increase the incidence of hypertension among salt-sensitive individuals[divided according to the average daily salt intake(＞11 g):58.8％vs.32.8％,P＜0.05;divided according to the quartile of daily salt intake:58.8％vs.32.8％,P＜0.05],but had no effect on salt-insensitive individuals(P＞0.05).Conclusion A high-salt diet can increase systolic blood pressure and diastolic blood pressure in salt-sensitive individuals,and significantly increase the long-term prevalence of hypertension in salt-sensitive individuals,but not in salt-insensitive individuals.Therefore,the salt-sensitive phenotype plays a crucial role in the relationship between salt intake and salt-sensitive hypertension.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

【Objective】 To explore the relationship between plasma adiponectin levels and hypertension based on the Hanzhong adolescent hypertension cohort. 【Methods】 A total of 361 young individuals with normal renal function， aged 32 to 41 years old， were taken as the research subjects. We collected or measured data including general characteristics， blood pressure （BP）， height， weight， pulse rate， and biochemistry indexes such as fasting glucose， blood lipid and plasma hs-CRP. The concentration of plasma adiponectin was determined by ELISA method. Binary logistic regression was performed to analyze the relationship between plasma adiponectin and hypertension. 【Results】 The plasma adiponectin level in patients with hypertension was significantly lower than that in normotensive patients ［3.56 （2.57-5.02）） μg/mL vs. 4.82 （3.19-6.89） μg/mL， P=0.012］. Partial correlation analysis showed a weak correlation of plasma adiponectin level with systolic BP and diastolic BP （r=-0.155， P=0.003 and r=-0.144， P=0.006）. Binary logistic regression analysis showed that after adjusting for confounding factors such as age， BMI， and high-sensitivity C-reactive protein， the risk of hypertension was 2.46 times higher in patients with plasma adiponectin in the lowest gender-specific tertile than those in the highest tertile （OR=2.46， 95% CI: 1.22-4.99）. 【Conclusion】 Hypoaponectinemia is an independent risk factor for hypertension in young individuals with normal renal function.

【Objective】 To explore the effects of dietary salt intake on serum and urinary levels through the chronic salt loading intervention. 【Methods】 Eighty adults （18 to 65 years old） were screened from two villages in Liquan and Lantian counties to participate in a 2-week chronic salt intervention， including a 3-day baseline survey， a 7-day low-salt diet， and a 7-day high-salt diet. Uromodulin levels in serum and urine were determined by enzyme-linked immunosorbent assay （ELISA） kits. According to the baseline blood pressure levels， all subjects were divided into normotensive and hypertensive groups. Pearson or Spearman correlation analyzed the associations of 24 h urinary sodium excretions with serum and urinary levels of uromodulin. 【Results】 At the baseline， serum uromodulin in hypertensive subjects was significantly lower than that in normotensive subjects （26.7±9.9 vs. 57.9±9.7 ng/mL， P=0.033）. Serum uromodulin levels were significantly lower on a high-salt diet than on a baseline diet ［（54.9±8.8 vs. 28.3±4.5） ng/mL， P=0.007］. In addition， daily urinary excretions of uromodulin were lower on a high-salt diet ［（28.4±6.6） ng/mL］ than on a baseline diet ［（282.1±70.0） ng/mL］ and on a low-salt diet ［（154.1±21.3） ng/mL］. The 24 h urinary sodium excretions were inversely correlated with urinary uromodulin excretions （r=-0.40， P<0.001） on both low-salt and high-salt diets， but not correlated with serum uromodulin levels. 【Conclusion】 Variations in dietary salt intake significantly affect plasma and urine uromodulin levels.