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Background and Aims: Insulin resistance (IR) has previously been associated with hypertension, and obesity is a risk factor for IR and hypertension. There is likely an association between body mass index (BMI) and risk for hypertension through the triglyceride-glucose (TyG) index but this relationship remains uncharacterized., Methods and Results: This study is based on the Hanzhong Adolescent Hypertension Cohort, which is an ongoing prospective study established in 1987. The TyG index was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/ 2 ]. The total area under the curve (AUCt) and incremental AUC (AUCi) were calculated as the long-term burden and trend of BMI, respectively. We found that BMI AUCt and BMI AUCi were significantly associated with the risk of adult hypertension, both without (RR = 1.30/1.31 for BMI AUCt/AUCi) and with (RR = 1.25/1.26 for BMI AUCt/AUCi) the inclusion of the TyG index as a covariate. Importantly, mediation analysis revealed that the TyG index mediated the BMI AUCt-SBP association (19.3%), the BMI AUCt-DBP association (22.7%), the BMI AUCi-SBP association (18.5%) and the BMI AUCi-DBP association (21.3%). Furthermore, the TyG index had a significant mediating effect of 15.9% on the BMI AUCt-hypertension association and 14.9% on the BMI AUCi-hypertension association., Conclusion: These findings suggest that the TyG index plays an important mediating role in the association between the cumulative burden and increasing trends of BMI originating in childhood and the risk of hypertension in midlife. We emphasize that early weight management has the potential to reduce the burden of hypertension caused by IR., Trial Registration: The study was clinically registered at the ClinicalTrials.gov (NCT02734472) and approved by the Academic Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2015LSL-047)., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G-protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14-year follow-up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt-induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high-salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14-year follow-up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06-2.87, p = .029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Normoalbuminuria has recently been associated with increased cardiovascular risk, and vascular aging is proposed as the early manifestation of cardiovascular disease. Here, the authors aimed to examine the association of high-normal albuminuria and vascular aging in a Chinese cohort. From our previously established cohort, 1942 participants with estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 or urinary albumin-creatinine ratio (UACR) <30 mg/g were enrolled. Brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s and/or carotid intima-media thickness (CIMT) ≥0.9 mm were used as indicators of vascular aging. Multivariate regression and receiving operating characteristic curve analysis were performed to examine the relationship between continuous and categorical UACR with vascular aging. We found an average UACR value of 8.08 (5.45-12.52) mg/g in this study. BaPWV and CIMT demonstrated positive correlations with lg-UACR (p < .05). High-normal albuminuria (10-29 mg/g) was significantly associated with the presence of vascular aging after adjusting for multiple cardiovascular confounders (OR = 1.540, 95% CI = 1.203-1.972, p = .001). In addition, a lg-UACR cutoff point of 0.918 lg(mg/g) (equal to UACR of 8.285 mg/g) was significantly associated with the presence of vascular aging and its components for all participants and those without hypertension or diabetes and without medication (p < .05). Briefly, high-normal albuminuria was significantly associated with vascular aging in this sample of Chinese adults. These findings implied the warning of elevated UACR even within normal range in clinical practice and the importance of UACR screening in normoalbuminuria for early detection and prevention of cardiovascular disease in otherwise healthy participants., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers blood pressure (BP) and exert a salutary effect on the salt sensitivity of BP. This study aimed to examine the associations of SGLT2 genetic variants with salt sensitivity, longitudinal BP changes and the risk of incident hypertension in Baoji Salt-Sensitive Study. A total of 514 participants were recruited when the cohort was established in 2004, and 333 participants received a dietary intervention that consisted of a 3-day usual diet followed sequentially by a 7-day low-salt diet and a 7-day high-salt diet. The cohort was then followed up for 14 years to evaluate the longitudinal BP changes and development of hypertension. We found that SGLT2 SNP rs3813007 was significantly associated with the systolic BP (SBP) responses to the low-salt diet. Over the 14 years of follow-up, SNPs rs3116149 and rs3813008 were significantly associated with the longitudinal SBP changes, and SNPs rs3116149, rs3813008, rs3813007 in SGLT2 were significantly associated with incidence of hypertension. Furthermore, gene-based analyses revealed that SGLT2 was significantly associated with hypertension incidence. Our study suggests that SGLT2 genetic polymorphisms may be involved in salt sensitivity and development of hypertension., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Transient high salt intake causes a sustained increase in blood pressure (BP) even after returning to a normal-salt diet, a phenomenon known as "salt memory." However, the molecular mechanisms of this phenomenon remain to be elucidated. Dahl salt-sensitive (SS) rats were fed a high-salt (8% NaCl) or high-salt diet and treated with drugs for 8 to 16 weeks and then returned to a normal-salt diet for 3 months. This study investigated the molecular mechanisms of salt memory and its mediation of SS hypertension and renal damage. We show that transient high salt intake caused persistent elevation of BP and exacerbation of kidney damage in Dahl SS rats even after returning to a normal-salt diet. Both epigenetic changes and inflammatory activation also persisted after resumption of a normal diet. Arterial BP, renal injury and the inflammatory response returned to normal levels in rats administered mycophenolate mofetil (MMF) during the 8-week period of high salt intake, resulting in the disappearance of salt memory. However, the vasodilator hydralazine did not ameliorate kidney damage or inflammatory activation, although it decreased BP to control levels. Transient high salt intake increased histone 3 lysine 4 monomethylation (H3K4me1) levels at the nuclear factor κB (NF-κB) subunit p65 promoter in SS rats, promoting p65 gene transcription and NF-κB activation and further leading to a series of inflammatory responses. Our findings demonstrate that transient high salt-induced epigenetic changes and persistent inflammatory activation play important roles in salt memory and its mediation of SS hypertension and renal damage., Competing Interests: Declaration of competing interests The authors declare that there are no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Early vascular aging (EVA) increases cardiovascular mortality, but its long-term determinants are unknown. We included 2098 participants with ≥4 blood pressure (BP) measurements from childhood to adulthood (from the Hanzhong Adolescent Hypertension Cohort study) to investigate the impact of child-to-adult cumulative BP exposure on EVA patterns in midlife. Participants with EVA had significantly higher long-term BP burden than those with normal vascular age in midlife despite being much younger. Child-to-adult cumulative burden and trends of systolic and diastolic BP were associated with vascular age (standardized regression coefficient [β] = .31 to .53; P < .001 for all). Higher cumulative systolic and diastolic BP exposure significantly increased the risk of EVA in midlife (odds ratio, OR=1.67 to 2.75, P < .05 for all). All associations were independent of socio-demographics and cardiovascular risk factors. Excluding participants who were receiving anti-hypertensive, antidiabetic, or lipid-lowering treatments did not substantially change the above associations. This study, for the first time, reported that high cumulative child-to-adult BP exposure accelerated the vascular aging process. Stabilizing BP across life course could be beneficial to vascular health in the long run.

Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), a member of the E3 ubiquitin-protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt-sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt-Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high-salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow-up. SNP rs292449 was significantly associated with hypertension incidence over the 14-year follow-up. Finally, this gene-based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14-year follow-up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Data on the association of isolated diastolic hypertension (IDH) in childhood with adult cardiovascular risk are scarce. This study aimed to estimate the prevalence of IDH in adolescents and to explore the impact of IDH in childhood on adult subclinical target organ damage (STOD)., Methods: This longitudinal study consisted of 1738 school children (55.4% boys) aged 6-15 years from rural areas of Hanzhong, Shaanxi, who were followed for 30 years. Their blood pressure was recorded to define the hypertension subtypes: normotension, IDH, isolated systolic hypertension (ISH) and mixed hypertension. Tracked STOD included arterial stiffness ( n  = 1738), albuminuria ( n  = 1652) and left ventricular hypertrophy (LVH) ( n  = 1429)., Results: Overall, the prevalence of IDH, ISH and mixed hypertension was 5.4, 2.2 and 3%, respectively, and there was no gender difference. Over 30 years, 366 (21.1%) of participants developed arterial stiffness, 170 (10.3%) developed albuminuria and 68 (4.8%) developed LVH. Compared with normotensive participants, IDH in childhood had higher risk ratio (RR) of experiencing arterial stiffness (RR, 1.66; 95% CI, 1.01-2.76) and albuminuria (RR, 2.27; 95% CI, 1.35-4.16) in adults after being fully adjusted but not LVH. However, if the elevated blood pressure in children was used as the reference standard, IDH in childhood was associated with adult LVH (RR, 2.48; 95% CI, 1.28-4.84)., Conclusion: IDH accounts for a higher proportion of adolescent hypertension subtypes and can increase the risk of adult STOD. These results highlight the necessity of improving the prevention, detection and treatment of IDH in adolescents., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood., Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m 2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g., Results: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SD SBP , ARV SBP , SD DBP , ARV DBP , SD MAP , ARV MAP , and ARV PP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up., Conclusions: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.

Background: The triglyceride-glucose index (TyG index) has emerged as a reliable surrogate marker of insulin resistance associated with arterial stiffness. However, most studies were based on a cross-sectional design, and few studies have evaluated the longitudinal impact of the TyG index on arterial stiffness. This study aimed to investigate the associations of single time point measurement and the long-term trajectory of the TyG index with arterial stiffness in a Chinese cohort., Methods: Data are derived from the Hanzhong Adolescent Hypertension Cohort study. A total of 2480 individuals who participated in the 2017 survey was included in the cross-sectional analysis. A sample of 180 individuals from the sub-cohort with follow-up data in 2005, 2013, and 2017 was enrolled in the longitudinal analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2), and arterial stiffness was determined using brachial-ankle pulse wave velocity (baPWV). The latent class growth mixture modeling method was used to identify the TyG index trajectories from 2005 to 2017., Results: In the cross-sectional analysis, the median age of the study population was 42.8 (39.8, 44.9) years, and 1351 (54.5%) were males. Each one-unit increment in TyG index was associated with a 37.1 cm/s increase (95% confidence interval [CI] 23.7-50.6 cm/s; P < 0.001) in baPWV, and similar results were observed when the TyG index was in the form of quartiles. In the longitudinal analysis, we identified three distinct TyG index trajectories and found that the highest TyG index trajectory carried the greatest odds of increased arterial stiffness, with a fully adjusted odds ratio (OR) of 2.76 (95% CI 1.40, 7.54)., Conclusions: Elevated levels of baseline TyG index and higher long-term trajectory of TyG index were independently associated with increased arterial stiffness. Monitoring immediate levels and longitudinal trends of the TyG index may help with the prevention of arterial stiffness in the long run., (© 2022. The Author(s).)

Corin, a transmembrane serine protease that can cleave pro-atrial natriuretic peptide (Pro-ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt-Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7-day low salt diet (3 g/day) and a 7-day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low-salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low-salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high-salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow-up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene-based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8-year follow-up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The pulsatile stress in the microcirculation may contribute to development or progression of chronic kidney disease. However, there is no prospective data confirming whether pulsatile stress in early life affect renal function in middle age. The authors performed a longitudinal analysis of 1738 participants aged 6-15 years at baseline, an ongoing Adolescent Prospective Cohort with a follow-up of 30 years. The authors evaluated the association between pulsatile stress in childhood and adult subclinical renal damage (SRD), adjusting for related covariates. Pulsatile stress was calculated as resting heart rate × pulse pressure. Renal function was assessed with estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR). The results showed that pulsatile stress in childhood was associated with adult SRD (Relative Risk, 1.43; p = .032), and the predictive value of combined pulse pressure and heart rate for SRD was higher than either of them alone. The high pulsatile stress in childhood increased the risk of adult SRD in males (RR, 1.92; p = .003), but this association was not found in females (RR, 0.91; p = .729). Further, the participants were categorized into four groups on the basis of pulsatile stress status in childhood and adulthood. Male patients with high pulsatile stress during childhood but normal pulsatile stress as adults still had an increased risk of SRD (RR, 2.04; 95% CI, 1.18-3.54), while female patients did not (RR, 0.96; 95% CI, 0.46-1.99). The study demonstrated that high pulsatile stress in childhood significantly increased the risk of adult SRD, especially in males. Adequate control of pulse pressure and heart rate from childhood, in the long-term, is very important for preventing kidney damage., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objective: Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans., Methods: Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years., Results: The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up., Conclusions: This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Stage 1 hypertension, newly defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline, has been the subject of significant interest globally. This study aims to assess the impact of the new blood pressure (BP) stratum on subsequent subclinical cardiovascular outcomes in low-risk young adults. This longitudinal study consisted of 1020 young adults (47.7% female; ages 18-23 years) free of cardiovascular disease from the Hanzhong Adolescent Hypertension Cohort with up to 25-year follow-up since 1992-1995. Outcomes were available through June 2017. Young adults with stage 1 hypertension accounted for 23.7% of the cohort. When it comes to middle adulthood, subjects with early life stage 1 hypertension were more likely to experience BP progression, and they had a 1.61-fold increased risk of high-risk brachial-ankle pulse wave velocity (baPWV) and a 2.92-fold risk of left ventricular hypertrophy (LVH) comparing with their normotensive counterparts. Among participants without any active treatment in midlife, the risk associated with stage 1 hypertension for BP progression was 2.25 (95% confidence interval [CI] = 1.41-3.59), high-risk baPWV was 1.58 (95% CI = 1.09-2.79), LVH was 2.75 (95% CI = 1.16-6.48), and subclinical renal damage (SRD) was 1.69 (95% CI = 1.02-2.82) compared with the normal BP group. Overall, young adults with stage 1 hypertension had significantly higher risks for midlife subclinical cardiovascular outcomes than normotensive subjects. BP management targeting low-risk young adults is of importance from both clinical and public health perspectives., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objective: The relationship between child-to-adult blood pressure (BP) trajectories and metabolic syndrome (MetS) is unknown. We aimed to determine the predictive role of BP trajectories for incident MetS and its components., Methods: The prospective Hanzhong Adolescent Hypertension study began in 1987 and included 2692 participants free of MetS at baseline with at least 3 BP measurements available from 1987 to 2017., Results: The systolic BP (SBP) trajectory patterns were grouped as normal (class 1, 18.7%), high normal (class 2, 60.3%), prehypertensive (class 3, 13.1%), stage 1 hypertensive (class 4, 5.7%), and stage 2 hypertensive (class 5, 2.2%). Compared with those in the normal group, individuals in classes 2 to 5 had significantly higher risks of MetS (all Ps < .05), and those with hypertension had more than an 8-fold higher risk of MetS (both P < .05). The fully adjusted risk ratios (RRs) of central obesity increased significantly in a stepwise manner as the SBP trajectory group increased from class 1 to class 5 (P < .05). Compared with those with a normal SBP trajectory, participants in the prehypertensive group and stage 1 and stage 2 hypertensive groups had significantly higher RRs for high-risk triglycerides after full adjustment (RR = 1.89 [1.22-2.94]; RR = 3.61 [2.16-6.02]; and RR = 3.22 [1.52-6.84], respectively)., Conclusion: Our study suggests that BP trajectories are predictive of incident MetS outcomes. Early detection of hypertension or modest elevations in BP is crucial. The stage of hypertension based on SBP level showed a greater association with central obesity., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time., Subjects/methods: To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD., Results: In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR)., Conclusions: In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.

Objective: Cyclooxygenase (COX)-2, an inducible isoform of the major rate-limiting enzymes that regulate the production of prostaglandins is associated with injury, inflammation and proliferation. We sought to examine whether plasma COX-2 levels and its genetic variants is associated with salt sensitivity, BP changes and/or hypertension in humans., Methods: Eighty participants (aged 18-65 years) were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families from seven Chinese villages in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension., Results: Plasma COX-2 levels were significantly decreased with reduction of salt intake from the usual to a low-salt diet and decreased further when converting from the low-salt to the high-salt diet. SNPs rs12042763 in the COX-2 gene was significantly associated with SBP responses to both low-salt and high-salt diet. SNPs rs689466 and rs12042763 were significantly associated with longitudinal changes in BPs. In addition, several COX-2 SNPs were significantly associated with incident hypertension over an 8-year follow-up. Gene-based analyses also supported the overall association of COX-2 with longitudinal changes in SBP and hypertension incidence., Conclusion: This study shows that dietary salt intake affects plasma COX-2 levels and that COX-2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations studied.

Background: A high atherogenic index of plasma (AIP) is associated with increased cardiovascular risk and higher serum uric acid levels, but whether AIP is a strong risk factor for developing subclinical renal damage (SRD) is unknown. This study aimed to explore the effect of AIP variations on the prevalence of SRD in a 12-year follow-up study., Methods: (1) The cross-sectional study enrolled 2485 participants from the Hanzhong cohort in 2017; (2) A total of 202 participants were included in the small longitudinal cohort from 2005 to 2017. Longitudinal analysis was used to determine whether an elevated AIP predicts the development of SRD., Results: In the cross-sectional analysis, the AIP level was correlated with the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (uACR) (P < 0.05). The age-adjusted odds ratio (OR) for prevalent SRD in men in the high AIP group was 1.924 (1.355-2.732) (P < 0.001), while in women, the OR was 1.616 (1.049-2.490) (P = 0.030) in the high AIP group. In the longitudinal analysis, significantly higher uACR levels were found in participants with normal AIP at baseline and elevated AIP in 2013 (P < 0.05). The adjusted OR for prevalent SRD in the incident AIP group was 4.741 (1.668-13.472) (P = 0.003) compared with the control group., Conclusions: Our study indicates that elevated AIP increased the risk of developing SRD and was associated with uACR and eGFR. As a simple marker of CVD risk, AIP may emerge as a novel and reliable indicator of SRD.

Background and Objectives: The aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort., Methods: 1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline., Results: In cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255-5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline., Conclusions: This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects., Competing Interests: The authors have declared that no competing interests exist.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife. Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years. Distinct trajectories of systolic blood pressure (SBP), body mass index (BMI), and heart rate from childhood to midlife were identified by group-based trajectory modeling. Vascular aging was assessed by carotid intima media thickness or brachial-ankle pulse wave velocity. Results: We identified 4 distinct SBP trajectories, 3 distinct BMI trajectories, and 2 distinct heart rate trajectories from childhood to midlife. Persistently increasing SBP, high-increasing BMI, and high-stable heart rate were all shown to have a positive association with brachial-ankle pulse wave velocity in midlife. For carotid intima–media thickness, similar associations were observed for persistently increasing SBP and high-increasing body mass index. After further adjustment for SBP, body mass index and heart rate at the time of vascular assessment in 2017, associations were also observed for cardiovascular risk factor trajectories accumulation with brachial-ankle pulse wave velocity (β, 0.656 [95% CI, 0.265–1.047]) and with carotid intima media thickness (β, 0.045 [95% CI, 0.011–0.079]) in adulthood. Conclusions: Longitudinal exposure to individual cardiovascular risk factors from childhood to midlife and cardiovascular risk factor accumulation were associated with an increased risk of vascular aging in midlife. Our study lends support for early targeting of risk factors in order to prevent cardiovascular disease later in life. [ABSTRACT FROM AUTHOR]

Background/Aims: Excess dietary salt is a critical risk factor of salt-sensitive hypertension. Glucagon-like peptide-1 (GLP-1), a gut incretin hormone, conferring benefits for blood pressure by natriuresis and diuresis. We implemented a randomized trial to verify the effect of altered salt intake on serum GLP-1 level in human beings. Methods: The 38 subjects were recruited from a rural community of Northern China. All subjects were sequentially maintained a baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of NaCl), and a high-salt diet period for additional 7 days (18.0g/day of NaCl). Results: Serum GLP-1 level increased significantly with the change from the baseline period to the low-salt diet period and decreased with the change from the low-salt to high-salt diet in normotensive saltsensitive (SS) but not salt-resistant (SR) individuals. There was a significant inverse correlation between the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the serum GLP-1 level and 24-h urinary sodium excretion was also found among different dietary interventions in SS subjects. Conclusions: Our study indicates that variations in dietary salt intake affect the serum GLP-1 level in normotensive salt-sensitive Chinese adults. [ABSTRACT FROM AUTHOR]

Objective: To identify distinct body mass index (BMI) trajectories across the life-course and explore the effects of BMI trajectories on the adult cardiovascular disease outcomes using a dataset with 30 years of follow-up in northern China.Study Design: A total of 2839 participants aged 6-18 years whose BMIs were measured 3-6 times during the Hanzhong Adolescent Hypertension Study were included in our analysis. Latent mixture modeling was used to clarify distinct BMI trajectories in longitudinal analyses.Results: Three groups with distinct trajectories in BMI were identified by the latent mixed models: a low-increasing group (n = 1324 [36.64%]), a moderate-increasing group (n = 1178 [16.89%]), and a high-increasing group (n = 337 [39.46%]). Compared with the participants in the low-increasing group, the risk ratios of hypertension, type 2 diabetes mellitus, high-risk triglycerides, and high-risk high-density lipoprotein cholesterol were more than 3.0 in the high-increasing group (all P < .001) after being fully adjusted. Increased risks existed in high brachial-ankle pulse wave velocity for the high-increasing group compared with the low-increasing group (RR, 2.75; 95% CI, 1.94-3.91; P < .001). Additionally, participants in the moderate-increasing group had a 2.31-fold increased risks of left ventricular hypertrophy (95% CI, 1.25-4.30; P = .008).Conclusions: Our study indicates that BMI trajectories from childhood to adulthood vary and that an elevated BMI trajectory in early life is predictive of an increased the risk of developing cardiovascular disease risks.Trial Registration: ClinicalTrials.gov: NCT02734472. [ABSTRACT FROM AUTHOR]

Background. Hyperuricemia has long been associated with increased cardiovascular risk, and arterial stiffness is proposed as a mediator. The present study is aimed at examining the associations of uric acid (UA) in blood and urine with arterial stiffness in a Chinese cohort. Methods. A total of 2296 participants (mean age: 43.0 years) from our previously established cohort of Hanzhong Adolescent Hypertension Study were included. The participants were classified as subjects with or without arterial stiffness, which was defined as brachial-ankle pulse wave velocity baPWV ≥ 1400 cm / s and/or carotid intima-media thickness CIMT ≥ 0.9 mm. Multivariate regression analyses were used to examine the relationship between serum and urinary UA and the risk of arterial stiffness after adjusting for age, gender, systolic blood pressure, fasting glucose, BMI, heart rate, total cholesterol, and triglycerides. Results. baPWV was positively correlated with urinary uric acid/creatinine ratio (uUA/Cre) (β = 0.061 , P < 0.001), while CIMT was correlated with uUA/Cre (β = 0.085 , P < 0.001) and fractional excretion of uric acid (FEUA) (β = 0.044 , P = 0.033) in all subjects. In addition, uUA/Cre was significantly associated with the risk of high baPWV [1.032 (1.019-1.045)] and arterial stiffness [1.028 (1.016-1.040)]. Conclusion. Our study showed that urinary UA excretion was significantly associated with the risk of arterial stiffness in Chinese adults. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of arterial stiffness in otherwise healthy subjects. [ABSTRACT FROM AUTHOR]