Associations of blood pressure trajectories in early life with target organ damage in midlife : a 30-year cohort study.

Hypertension is a pivotal factor in cardiovascular risk. However, the association of longitudinal blood pressure (BP) trajectories in the early life and cardiovascular risk assessed by target organ damage (TOD) in adulthood is poorly reported. The objective of this study was to identify the association between systolic BP, diastolic BP, and mean atrial pressure (MAP) trajectories early in life with a single or multiple TOD in later life. We identified BP trajectories from 6 to 45 year-old using group-based trajectory models among 2430 individuals in the Hanzhong Adolescent Hypertension Study and examined the relationship between BP trajectories and cardiovascular risk in later life. Four discrete long-term systolic BP, diastolic BP, and MAP trajectories were identified, namely, low stable, moderate stable, high stable (low increasing), and moderate increasing groups, based on the BP levels at baseline and in the 30-year follow-up. The carotid intima-media thickness were higher in persistently high or increasing trajectories in comparison to the low stable group. Individuals with deteriorative trajectories during early life were at an increased risk of suffering from a single TOD, including left ventricular hypertrophy (LVH) and carotid atherosclerosis (CA) in middle age (36-49 years old). Moreover, higher BP trajectories were correlated with the presence of combined TODs load stage which were assessed by CA, LVH, arteriosclerosis and subclinical renal damage (SRD). Higher longitudinal BP trajectories early in life were associated with increased cardiovascular risk in midlife, and identifying BP trajectories in early life can help screen individuals with TOD later. LVH, left Ventricular Hypertrophy; CA, carotid atherosclerosis; SRD, subclinical renal damage; TOD, target organ damage.

E2F2 is upregulated by the ERK pathway and regulates decidualization via MCM4.

Cell cycle modulation is an important event during decidualization. E2F2 is a transcription regulator that plays a vital role in cell cycle regulation. However, the biological role of E2F2 in decidualization has not yet been identified. In this study, estrogen (E2) and progestin (P4)-induced in vitro and in vivo decidualization models were applied. Our data showed that the expression levels of E2F2 and its downstream target MCM4 were downregulated in the uterus tissues of E2P4-treated mice compared with control mice. In hESCs, exposure to E2P4 resulted in a significant decrease in E2F2 and MCM4 expression. E2P4 treatment reduced hESC proliferation and ectopic expression of E2F2 or MCM4 elevated the viability of E2P4-treated hESCs. In addition, ectopic expression of E2F2 or MCM4 restored the expression of G1 phase-associated proteins. The ERK pathway was inactivated in E2P4-treated hESCs. Treatment with ERK agonist Ro 67-7476 restored the expression of E2F2, MCM4, and G1 phase-associated proteins that were inhibited by E2P4. Moreover, Ro 67-7476 retracted the levels of IGFBP1 and PRL that were induced by E2P4. Collectively, our results indicate that E2F2 is regulated by ERK signaling and contributes to decidualization via regulation of MCM4. Therefore, E2F2/MCM4 cascade may serve as promising targets for alleviating decidualization dysfunction.

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.

Association of rate pressure product trajectories at an early age with left ventricular hypertrophy in midlife: a prospective cohort study.

The joint effect of blood pressure (BP) and heart rate (HR) on cardiovascular disease is unclear. Rate pressure product (RPP), the product of systolic BP and HR, is assessed in this study. This study aimed to determine the longitudinal patterns of RPP from childhood to adulthood and to explore the relationship between RPP trajectories in early life and left ventricular hypertrophy (LVH) in midlife. We included individuals with 3 or more RPP values from 7 visits over a 30-year follow-up period in the Hanzhong Adolescent Hypertension Study cohort to fit trajectory groups and performed logistic regression to evaluate the relative risk of developing LVH. Three discrete trajectories in RPP were identified among 2412 participants assessed from childhood to middle-aged adulthood, which were tagged as "low stable," "moderate stable," and "moderate increasing". A higher waist-to-hip ratio, smoking, alcohol consumption, hypertension, diabetes, and hyperlipidemia were associated with increased RPP trajectories. The Cornell voltage product was positively correlated with RPP in 2017 and was higher in the moderate-stable and moderate-increasing groups than in the low-stable group in RPP trajectories. Compared with the low-stable group, the ORs of LVH were 1.65 (1.13, 2.92) for the moderate-stable and 3.56 (2.26, 5.44) for the moderate-increasing group. Subjects with moderate-stable and moderate-increasing trajectories showed higher probabilities of LVH at an elderly age than those in the low stable trajectory group even after adjusting for multiple cardiovascular risk factors. RPP trajectories are identifiable from childhood and are associated with LVH in midlife. Monitoring RPP trajectories from early life may be an effective approach to predict cardiovascular health status later in life.

Blood Pressure Trajectories From Childhood to Youth and Arterial Stiffness in Adulthood: A 30-Year Longitudinal Follow-Up Study.

Background: This study aimed to identify the subgroups of individuals sharing similar blood pressure (BP) trajectories from childhood to youth and explore the associations of these trajectories with arterial stiffness in adulthood. Methods: A group-based trajectory model was used to identify BP trajectories among 2,082 individuals in the Hanzhong adolescent hypertension cohort by using BP values repeatedly measured at four visits from childhood (6-15 years) to youth (14-23 years). The brachial-ankle pulse wave velocity (baPWV) was examined 30 years after the baseline survey. Mixed linear regression models were used to examine the associations of these trajectories with adult baPWV. Results: Among the 2,082 individuals, three trajectory groups of systolic BP were identified as follows: the low-level group (n = 889), medium-level group (n = 1,021), and high-level group (n = 172). The baPWV in adulthood was higher in medium-level and high-level groups compared with the low-level group (1271.4 ± 224.7 cm/s, 1366.1 ± 249.8 cm/s vs. 1190.1 ± 220.3 cm/s, all p < 0.001). After adjustment for potential confounding factors, the association between baPWV and systolic BP trajectories was statistically significant (adjusted ß = 49.4 cm/s; p < 0.001 for the medium-level group and ß = 107.6 cm/s; p < 0.001 for the high-level group compared with the low-level group). Similar results were obtained for the association of baPWV with the trajectories of diastolic BP and mean arterial pressure (MAP), except for pulse pressure. Conclusion: Our investigation demonstrates different BP trajectories from childhood to youth and shows the trajectories of systolic BP, diastolic BP, and MAP are significant predictors of arterial stiffness in adulthood.

Isolated diastolic hypertension in childhood and risk of adult subclinical target organ damage: a 30-year prospective cohort study.

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.

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.

Effects of MaiLiuPian on carotid thrombosis in rats and acute pulmonary embolism in mice and its antithrombotic mechanism.

Mailiupian (MLP) is a new patent functional food that consists of Crataegi Fructus, Notoginseng Radix, and Ginkgo Folium, which was reported to be active in improving the microcirculation based on formulation screening. However, whether it is effective in inhibiting thrombus and its mechanism has not been evaluated. Therefore, in the present study, the models of arterial thrombosis induced by FeCl3 and the models of APE by ADP were established to evaluate the antithrombosis effect of MLP. Results showed that MLP markedly reduced the weight and size of wet thrombosis in FeCl3 -induced rats and decreased the recovery time from symptoms of APE mice. MLP was proved to prolong APTT, PT, TT and improve the levels of t-PA and 6-keto-PGF1α significantly, meanwhile, PAI-1 and TXB2 were reduced apparently. By comparing tail bleeding time, MLP showed antithrombotic effects, but without the risk of bleeding, taking aspirin as a control. PRACTICAL APPLICATIONS: Our experiments proved that MLP, a new patent health food, acted on both coagulation and fibrinolytic systems and the platelet aggregation to play antithrombosis roles, providing a theoretical basis for applications of MLP in preventing or curing thrombosis diseases.

Long-Term Blood Pressure Exposure From Childhood and Early Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

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 [ß] = .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.

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.

ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation.

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.

Association of pulsatile stress in childhood with subclinical renal damage in adults: A 30-year prospective cohort study.

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.

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.

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.

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.

Blood pressure and long-term subclinical cardiovascular outcomes in low-risk young adults: Insights from Hanzhong adolescent hypertension cohort.

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.

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.

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.

Identification of Candidate Biomarkers for Salt Sensitivity of Blood Pressure by Integrated Bioinformatics Analysis.

In the current study, we aimed to identify potential biomarkers for salt sensitivity of blood pressure (SSBP), which may provide a novel insight into the pathogenic mechanisms of salt-sensitive hypertension. Firstly, we conducted weighted gene coexpression network analysis (WGCNA) and selected a gene module and 60 hub genes significantly correlated to SSBP. Then, GO function and KEGG signaling pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed. Furthermore, we identified a five-gene signature with high connectivity degree in the PPI network and high AUC of ROC curves, which may have high diagnosis value for SSBP. Moreover, through combining two gene screening methods, we identified 23 differentially expressed circRNAs and selected the top 5% circRNAs (1 circRNA) with the highest connectivity degree in the coexpression network as hub circRNA highly associated with SSBP. Finally, we carried out RT-qPCR to validate the expression of five hub genes, and our results showed that the expression of HECTD1 (P = 0.017), SRSF5 (P = 0.003), SRSF1 (P = 0.006), HERC2 (P = 0.004), and TNPO1 (P = 0.002) was significantly upregulated in the renal tissue in salt-sensitive rats compared to salt-resistant rats, indicating that these five hub genes can serve as potential biomarkers for SSBP.