Long-term burden and increasing trends of body mass index are linked with adult hypertension through triglyceride-glucose index: A 30-year prospective cohort study.

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).

The new visceral adiposity index outperforms traditional obesity indices as a predictor of subclinical renal damage in Chinese individuals: a cross-sectional study.

BACKGROUND: The new visceral adiposity index (NVAI) was superior to previous obesity indices in predicting cardiovascular diseases among Asians. Nevertheless, the utility of the NVAI for predicting chronic kidney disease is still unclear. The objective of this research was to explore the relationship between the NVAI and subclinical renal damage (SRD) and to investigate whether the NVAI outperforms other common obesity indices in predicting SRD in the Chinese population. METHODS: Participants in this cross-sectional study were from the Hanzhong Adolescent Hypertension Cohort. The NVAI and seven other common obesity indices were calculated, including body mass index, waist circumference, lipid accumulation product, visceral adiposity index, Chinese visceral adiposity index, a body shape index and metabolic score for visceral fat. Logistic regression models revealed the association between NVAI and SRD. The odds ratio (OR) and the 95% confidence interval (CI) were calculated to show the association between the two variables. The predictive power of eight obesity indices for SRD was evaluated through the receiver operating characteristic curve and area under the curve (AUC). In addition, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were also applied to compare the incremental predictive value for SRD of different obesity indices. RESULTS: The median age of the 2358 subjects was 42.00 years. Across NVAI tertiles, the prevalence of SRD was 7.25%, 11.21%, and 21.60%, respectively. After adjusting for confounders, a high level of NVAI remained a risk factor for SRD. The ORs of the middle and top NVAI tertiles for SRD were 1.920 (95% CI: 1.322, 2.787) and 4.129 (95% CI: 2.750, 6.202), respectively. The AUC of the NVAI was 0.666 (95% CI: 0.647, 0.685), which was significantly larger than the AUC of any of the other obesity indicators. Moreover, the NRI and IDI were significantly improved when NVAI was added to the basic model for predicting SRD. Among eight obesity indices, NVAI had the highest NRI (0.392; 95% CI: 0.280, 0.503), and its IDI (0.021; 95% CI: 0.014, 0.027) was second only to that of the body mass index (0.023; 95% CI: 0.014, 0.032). CONCLUSIONS: NVAI is independently and positively associated with SRD. Among the eight obesity indices, the NVAI shows the strongest predictive power for SRD in the Chinese population. The NVAI may be useful as an effective warning indicator of chronic kidney disease in Chinese adults.

Sex differences in impact of cumulative systolic blood pressure from childhood to adulthood on albuminuria in midlife: a 30-year prospective cohort study.

BACKGROUND AND OBJECTIVES: Albuminuria is recognized as being a predictor of cardiovascular and renal disease. We aimed to identify the impact of the long-term burden and trends of systolic blood pressure on albuminuria in midlife, as well as to explore sex differences concerning this relationship. METHODS: This longitudinal study consisted of 1,683 adults who had been examined 4 or more times for blood pressure starting in childhood, with a follow-up time period of 30 years. The cumulative effect and longitudinal trend of blood pressure were identified by using the area under the curve (AUC) of individual systolic blood pressure measurement with a growth curve random effects model. RESULTS: Over 30 years of follow-up, 190 people developed albuminuria, including 53.2% males and 46.8% females (aged 43.39 ± 3.13 years in the latest follow-up). The urine albumin-to-creatinine ratio (uACR) values increased as the total and incremental AUC values increased. Additionally, women had a higher albuminuria incidence in the higher SBP AUC groups than men do (13.3% for men vs. 33.7% for women). Logistic regression showed that the ORs of albuminuria for males and females in the high total AUC group were 1.34 (0.70-2.60) and 2.94 (1.50-5.74), respectively. Similar associations were found in the incremental AUC groups. CONCLUSIONS: Higher cumulative SBP was correlated with higher uACR levels and a risk of albuminuria in middle age, especially in women. The identification and control of cumulative SBP levels from an early age may assist in reducing the incidences of renal and cardiovascular disease for individuals in later life.

Triglyceride-glucose index trajectory and arterial stiffness: results from Hanzhong Adolescent Hypertension Cohort Study.

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.

Child-to-adult body mass index trajectories and the risk of subclinical renal damage in middle age.

BACKGROUND: Although it is well established that obesity is a risk factor for chronic kidney disease, the impact of distinct long-term body mass index (BMI) developmental patterns on renal function in later life is poorly understood. METHODS: This study utilized data derived from the Hanzhong Adolescent Hypertension Cohort, a prospective cohort followed over 30 years. We used latent class growth mixture modeling method to identify the BMI trajectories of participants who had received BMI measurements at least three times from childhood (age: 6-15 years) to adulthood (age: 36-45 years). The modified Poisson regression model was used to identify potential associations between BMI trajectories and subclinical renal damage (SRD) in midlife. RESULTS: Within a total of 2162 individuals, we identified four distinct long-term BMI trajectories: stable normal (54.72%), moderately increasing overweight (32.42%), resolving (10.27%), and progressively increasing obese (2.59%). By the latest follow-up in 2017, a total of 257 (13.1%) individuals were diagnosed with SRD. Compared with the stable normal group, the moderately increasing overweight group and the progressively increasing obese group exhibited significantly a higher urinary albumin-to-creatinine ratio and a higher odd of existing SRD in 2017 (risk ratio [RR], 1.70 [95% confidence interval (CI), 1.33-2.19] and 4.35 [95% CI, 3.00-6.30], respectively). However, individuals who resolved their elevated BMI in early life had a similar risk for SRD as those who had never been obese or overweight (RR, 1.17 [95% CI, 0.77-1.79]). CONCLUSIONS: Child-to-adult BMI trajectories that worsen or persist at high levels were associated with an increased risk for SRD in midlife. Maintaining a normal BMI or reversing an elevated BMI in early life may be beneficial to renal function over the long term.

Risk factors for electrocardiographic left ventricular hypertrophy in a young Chinese general population: the Hanzhong adolescent cohort study.

BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG-LVH) is a common manifestation of preclinical cardiovascular disease. The present study aimed to investigate risk factors for ECG-LVH and its prevalence in a cohort of young Chinese individuals. METHODS: (1) A total of 1515 participants aged 36-45 years old from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine risk factors for ECG-LVH and its prevalence. (2) A total of 235 participants were recruited from the same cohort in 2013 and were followed up in 2017. Longitudinal analysis was used to determine the predictors of LVH occurrence over the 4-year period. We used multivariable logistic regression models to calculate OR and 95% CIs and to analyze risk factors for ECG-LVH. RESULTS: In the cross-sectional analysis, the prevalence of LVH diagnosed by the Cornell voltage-duration product in the overall population and the hypertensive population was 4.6% and 8.8%, respectively. The logistic regression results shown that female sex [2.611 (1.591-4.583)], hypertension [2.638 (1.449-4.803)], systolic blood pressure (SBP) [1.021 (1.007-1.035)], serum uric acid (SUA) [1.004 (1.001-1.006)] and carotid intima-media thickness (CIMT) [67.670 (13.352-342.976)] were significantly associated with the risk of LVH (all P < 0.05). In the longitudinal analysis, fasting glucose [1.377 (1.087-1.754)], SBP [1.046 (1.013-1.080)] and female sex [1.242 (1.069-1.853)] were independent predictors for the occurrence of LVH in the fourth year of follow-up. CONCLUSIONS: Our study suggested that female sex, hypertension, SBP, SUA and CIMT were significantly associated with the risk of LVH in young people. In addition, fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in a young Chinese general population.

Long-term burden of higher body mass index from childhood on adult cardiometabolic biomarkers: A 30-year cohort study.

BACKGROUND AND AIMS: Data are limited regarding the association between long-term burden of higher body mass index (BMI) from childhood and cardiometabolic biomarkers. METHODS AND RESULTS: A total of 1553 individuals aged 6-15 years, who were examined 4 or more times for BMI since childhood and followed for 30 years were included in our analysis. Total area under the curve (AUCt) and incremental AUC (AUCi) were calculated as the long-term burden and trends of BMI. Cardiometabolic biomarkers including serum uric acid (SUA), fasting blood-glucose (FBG), and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were obtained from venous blood samples. The results showed a positive association of BMI AUCt and AUCi with cardiometabolic biomarkers. After adjusting for demographic variables, the AUCt and AUCi of BMI were significantly associated with a higher level of SUA (ß = 3.71; 2.87), FBG (ß = 0.09; 0.09), and TG/HDL-C (ß = 0.14; 0.11). We performed further studies after dividing subjects into four groups according to AUCt and AUCi of BMI by quartiles. Compared with the lowest quartile group, the highest quartile group had significantly increased risk ratios of hyperuricemia (RR = 2.01; 1.74), type 2 diabetes mellitus (RR = 8.18; 3.96), and high-risk TG/HDL-C (RR = 4.05; 3.26). CONCLUSION: Our study identifies all subjects' BMI growth curve from childhood and indicates that the long-term burden of higher BMI significantly increases the cardiometabolic risk, and the impact of excessive body weight on cardiometabolic health originates in early life. We emphasize the importance of weight control from childhood for cardiometabolic health.

Predictive Role of Child-To-Adult Blood Pressure Trajectories for Incident Metabolic Syndrome: 30-Year Hanzhong Adolescent Hypertension Study.

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.

Association of body mass index changes from childhood to adulthood with dyslipidemia in adults: Hanzhong adolescent cohort study.

BACKGROUND: Dyslipidemia is a disorder of lipid metabolism and associated with insulin resistance. The relationship between longitudinal body mass index (BMI) changes from childhood to adulthood and long-term dyslipidemia was explored in this study. METHODS: We assessed the longitudinal relationship between BMI changes since childhood and dyslipidemia among 1738 participants in rural areas of Hanzhong City, Shaanxi. All participants were initially examined between the ages of 6 and 15 years in 1987 and were reexamined in 1995, 2013 and 2017; the total follow-up duration was 30 years. Anthropometric measurements and blood biochemistry indexes were measured. RESULTS: We found that gradual progression of normal weight to overweight (OR = 1.65; 95% CI = 1.27, 2.15) or persistent overweight (OR = 2.45; 95% CI = 1.52, 3.96) from childhood to adulthood was associated with an increased risk of dyslipidemia in adulthood. And these risks were largely disappeared if the overweight or obesity during childhood was resolved by adulthood. The higher the BMI in adulthood and the younger the age at which overweight begins, the higher the risk of dyslipidemia. CONCLUSIONS: Early weight loss and any degree of weight loss from childhood to adulthood can help improve dyslipidemia in adulthood. We further emphasize the importance of weight management and control in public health primary prevention.

Body Mass Index Trajectories in Early Life Is Predictive of Cardiometabolic Risk.

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.

Experience Sharing in Pathological Diagnosis of Early Adenocarcinoma of the Lung.

Background: In daily work, there are still many pathologists who have difficulty handling the diagnosis of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma, and the boundaries are not clear enough. Sometimes, the diagnosis is difficult, and there is sometimes poor reproducibility between different pathologists. Accurate diagnosis and differential diagnosis require a certain amount of experience. Methods: During the COVID-19 pandemic, we collected a large number (n = 381) of specimens of early lung adenocarcinoma, most of which (n = 356) were solitary lesions and 25 were multifocal lesions. There were 78 nodules in multifocal lesions, total 434 nodules. We summarized very careful microscopic observation and comparative analysis on all frozen and paraffin sections collected from many early lung adenocarcinoma specimens, continuously summarizing our experience. Results: Based on the World Health Organization's 2021 classification and diagnostic criteria for lung adenocarcinoma, new perspectives have been proposed on how to distinguish between atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma. In particular, new perspectives have been proposed on how to identify invasive aspects, and there are also some new perspectives on early lung mucinous lesions. Conclusion: Atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma all have corresponding morphological diagnostic criteria, but the morphological boundaries are sometimes not easy to determine and require some experience accumulation. The intraoperative frozen pathological diagnosis of early adenocarcinoma of the lung needs to be closely combined with imaging examination, and has very rich morphological experience.

The association of long-term trajectories of BMI, its variability, and metabolic syndrome: a 30-year prospective cohort study.

Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987-June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings: BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63-6.91]) and high-increasing groups (13.11 [6.30-27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02-2.62], 1.22 [1.19-1.26], and 4.29 [3.38-5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00-2.23]) and high-increasing groups (2.45 [1.22-4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08-1.42], 1.00 [1.00-1.01], and 1.21 [1.05-1.38]). Interpretation: Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife. Funding: This work was supported by the National Natural Science Foundation of China No. 82070437 (J.-J.M.), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021, and XJTU1AF-CRF-2023-004), the Key R&D Projects in Shaanxi Province (Grant No. 2023-ZDLSF-50), the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2), and the International Joint Research Centre for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

Associations of genetic variations in the M3 receptor with salt sensitivity, longitudinal changes in blood pressure and the incidence of hypertension in Chinese adults.

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.

A Novel and Noninvasive Risk Assessment Score and Its Child-to-Adult Trajectories to Screen Subclinical Renal Damage in Middle Age.

This study aimed to develop a noninvasive, economical and effective subclinical renal damage (SRD) risk assessment tool to identify high-risk asymptomatic people from a large-scale population and improve current clinical SRD screening strategies. Based on the Hanzhong Adolescent Hypertension Cohort, SRD-associated variables were identified and the SRD risk assessment score model was established and further validated with machine learning algorithms. Longitudinal follow-up data were used to identify child-to-adult SRD risk score trajectories and to investigate the relationship between different trajectory groups and the incidence of SRD in middle age. Systolic blood pressure, diastolic blood pressure and body mass index were identified as SRD-associated variables. Based on these three variables, an SRD risk assessment score was developed, with excellent classification ability (AUC value of ROC curve: 0.778 for SRD estimation, 0.729 for 4-year SRD risk prediction), calibration (Hosmer-Lemeshow goodness-of-fit test p = 0.62 for SRD estimation, p = 0.34 for 4-year SRD risk prediction) and more potential clinical benefits. In addition, three child-to-adult SRD risk assessment score trajectories were identified: increasing, increasing-stable and stable. Further difference analysis and logistic regression analysis showed that these SRD risk assessment score trajectories were highly associated with the incidence of SRD in middle age. In brief, we constructed a novel and noninvasive SRD risk assessment tool with excellent performance to help identify high-risk asymptomatic people from a large-scale population and assist in SRD screening.

Transient high salt intake causes epigenetic changes and leads to persistent inflammatory activation to produce "salt memory".

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.

Association of high-normal albuminuria and vascular aging: Hanzhong adolescent hypertension study.

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 m2 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.

Associations of SGLT2 genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.

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.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

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 (ß, 0.656 [95% CI, 0.265-1.047]) and with carotid intima media thickness (ß, 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.

Associations of lipid accumulation product, visceral adiposity index, and triglyceride-glucose index with subclinical organ damage in healthy Chinese adults.

Background and aims: Obesity is an independent risk factor for cardiovascular disease development. Here, we aimed to examine and compare the predictive values of three novel obesity indices, lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index, for cardiovascular subclinical organ damage. Methods: A total of 1,773 healthy individuals from the Hanzhong Adolescent Hypertension Study cohort were enrolled. Anthropometric, biochemical, urinary albumin-to-creatinine ratio (uACR), brachial-ankle pulse wave velocity (baPWV), and Cornell voltage-duration product data were collected. Furthermore, the potential risk factors for subclinical organ damage were investigated, with particular emphasis on examining the predictive value of the LAP, VAI, and TyG index for detecting subclinical organ damage. Results: LAP, VAI, and TyG index exhibited a significant positive association with baPWV and uACR. However, only LAP and VAI were found to have a positive correlation with Cornell product. While the three indices did not show an association with electrocardiographic left ventricular hypertrophy, higher values of LAP and TyG index were significantly associated with an increased risk of arterial stiffness and albuminuria. Furthermore, after dividing the population into quartiles, the fourth quartiles of LAP and TyG index showed a significant association with arterial stiffness and albuminuria when compared with the first quartiles, in both unadjusted and fully adjusted models. Additionally, the concordance index (C-index) values for LAP, VAI, and TyG index were reasonably high for arterial stiffness (0.856, 0.856, and 0.857, respectively) and albuminuria (0.739, 0.737, and 0.746, respectively). Lastly, the analyses of continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) demonstrated that the TyG index exhibited significantly higher predictive values for arterial stiffness and albuminuria compared with LAP and VAI. Conclusion: LAP, VAI, and, especially, TyG index demonstrated utility in screening cardiovascular subclinical organ damage among Chinese adults in this community-based sample. These indices have the potential to function as markers for early detection of cardiovascular disease in otherwise healthy individuals.

High Dietary Salt Intake Is Associated With Histone Methylation in Salt-Sensitive Individuals.

Background: High salt diet is one of the important risk factors of hypertension and cardiovascular diseases. Increasingly strong evidence supports epigenetic mechanisms' significant role in hypertension. We aimed to explore associations of epigenetics with high salt diet, salt sensitivity (SS), and SS hypertension. Methods: We conducted a dietary intervention study of chronic salt loading in 339 subjects from northern China in 2004 and divided the subjects into different salt sensitivity phenotypes. A total of 152 participants were randomly selected from the same cohort for follow-up in 2018 to explore the effect of a high-salt diet on serum monomethylation of H3K4 (H3K4me1), histone methyltransferase Set7, and lysine-specific demethylase 1 (LSD-1). Results: Among SS individuals, the blood pressure (SBP: 140.8 vs. 132.9 mmHg; MAP: 104.2 vs. 98.7 mmHg) and prevalence of hypertension (58.8 vs. 32.8%) were significantly higher in high salt (HS) diet group than in normal salt (NS) diet group, but not in the salt-resistant (SR) individuals (P > 0.05). Serum H3K4me1 level (287.3 vs. 179.7 pg/ml, P < 0.05) significantly increased in HS group of SS individuals, but not in SR individuals. We found daily salt intake in SS individuals was positively correlated with serum H3K4me1 (r = 0.322, P = 0.005) and Set7 (r = 0.340, P = 0.005) levels after adjusting for age and gender, but not with LSD-1 (r = -0.137, P = 0.251). In addition, positive correlation between the serum H3K4me1 level and Set7 level (r = 0.326, P = 0.007) was also found in SS individuals. These correlations were not evident in SR individuals. Conclusion: Our study indicates that high salt diet increases the serum H3K4me1 and Set7 levels in SS individuals.