Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial.

BACKGROUND: Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. METHODS: In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719. FINDINGS: Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001). INTERPRETATION: The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. FUNDING: The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.

A village doctor-led multifaceted intervention for blood pressure control in rural China: an open, cluster randomised trial.

BACKGROUND: The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care). METHODS: In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing. FINDINGS: Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p<0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p<0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p<0·0001). No treatment-related serious adverse events were reported in either group. INTERPRETATION: Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control. FUNDING: Ministry of Science and Technology of China.

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.

Lipid goal attainment in diabetes mellitus patients after acute coronary syndrome: a subanalysis of Dyslipidemia International Study II-China.

BACKGROUND: Lipid management with a low-density lipoprotein cholesterol (LDL-C) goal of < 1.4 mmol/L is recommended for patients with acute coronary syndrome (ACS) and diabetes mellitus (DM) due to a high risk for adverse cardiovascular events. This study evaluated the lipid-lowering treatment (LLT) pattern and the LDL-C goal attainment rate in this special population. METHODS: DM patients were screened from the observational Dyslipidemia International Study II-China study which assessed LDL-C goal attainment in Chinese ACS patients. The baseline characteristics between the LLT and no pre-LLT groups were compared. The proportions of patients obtaining LDL-C goal at admission and at 6-months, the difference from the goal, and the pattern of the LLT regimen were analyzed. RESULTS: Totally 252 eligible patients were included, with 28.6% taking LLT at admission. Patients in the LLT group were older, had a lower percentage of myocardial infarction, and had decreased levels of LDL-C and total cholesterol compared to those in the no pre-LLT group at baseline. The overall LDL-C goal attainment rate was 7.5% at admission and increased to 30.2% at 6 months. The mean difference between the actual LDL-C value and LDL-C goal value dropped from 1.27 mmol/L at baseline to 0.80 mmol/L at 6 months. At 6 months, 91.4% of the patients received statin monotherapy, and only 6.9% received a combination of statin and ezetimibe. The atorvastatin-equivalent daily statin dosage was moderate during the study period. CONCLUSION: The low rate of lipid goal attainment observed was in line with the outcomes of other DYSIS-China studies.

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.

Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression.

OBJECTIVES: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. METHODS: We conducted family-based dietary interventions among 344 participants from 126 families in rural villages of northern China in 2004. Subjects sequentially underwent a baseline diet, a low-salt diet (51.3 mmol/day Na), a high-salt diet (307.8 mmol/day Na), and a high-salt + potassium supplementation diet (307.8 mmol/day Na + 60 mmol/day K). After dietary intervention, we followed up with these participants in 2009 and 2012. The associations between 6 single-nucleotide polymorphisms (SNPs) of KL and phenotypes were analyzed through a linear mixed-effects model. RESULTS: SNPs rs211247 and rs1207568 were positively correlated with the BP response to high-salt diet in the dominant model after adjusting for confounders (ß = 1.670 and 2.163, p = 0.032 and 0.005, respectively). BPs rs526906 and rs525014 were in a haplotype block. Block rs526906-rs525014 was positively correlated with diastolic BP response to potassium and potassium sensitivity in the additive model (ß = 0.845, p = 0.032). In addition, regression analysis indicated that rs211247 was associated with long-term systolic BP alterations after 8 years of follow-up in the recessive model (ß = 20.47, p = 0.032). CONCLUSIONS: Common variants of the KL gene might modify individual BP sensitivity to sodium or potassium and influence the long-term progression of BP, suggesting a potential role in the development of salt-sensitive hypertension. Thus, KL may be a new early intervention target for salt-sensitive hypertension.

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.

Hydrogen sulfide restores cardioprotective effects of remote ischemic preconditioning in aged rats via HIF-1α/Nrf2 signaling pathway.

The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S.The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

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.

LncRNA TNK2-AS1 regulated ox-LDL-stimulated HASMC proliferation and migration via modulating VEGFA and FGF1 expression by sponging miR-150-5p.

Long non-coding RNAs (lncRNAs) have been indicated for the regulatory roles in cardiovascular diseases. This study determined the expression of lncRNA TNK2 antisense RNA 1 (TNK2-AS1) in oxidized low-density lipoprotein (ox-LDL)-stimulated human aortic smooth muscle cells (HASMCs) and examined the mechanistic role of TNK2-AS1 in the proliferation and migration of HASMCs. Our results demonstrated that ox-LDL promoted HASMC proliferation and migration, and the enhanced proliferation and migration in ox-LDL-treated HASMCs were accompanied by the up-regulation of TNK2-AS1. In vitro functional studies showed that TNK2-AS1 knockdown suppressed cell proliferation and migration of ox-LDL-stimulated HASMCs, while TNK2-AS1 overexpression enhanced HASMC proliferation and migration. Additionally, TNK2-AS1 inversely regulated miR-150-5p expression via acting as a competing endogenous RNA (ceRNA), and the enhanced effects of TNK2-AS1 overexpression on HASMC proliferation and migration were attenuated by miR-150-5p overexpression. Moreover, miR-150-5p could target the 3' untranslated regions of vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) to regulate FGF1 and VEGFA expression in HASMCs, and the inhibitory effects of miR-150-5p overexpression in ox-LDL-stimulated HASMCs were attenuated by enforced expression of VEGFA and FGF1. Enforced expression of VEGFA and FGF1 also partially restored the suppressed cell proliferation and migration induced by TNK2-AS1 knockdown in ox-LDL-stimulated HASMCs, while the enhanced effects of TNK2-AS1 overexpression on HASMC proliferation and migration were attenuated by the knockdown of VEGFA and FGF1. Collectively, our findings showed that TNK2-AS1 exerted its action in ox-LDL-stimulated HASMCs via regulating VEGFA and FGF1 expression by acting as a ceRNA for miR-150-5p.

Joint Association of Serum Homocysteine and High-Sensitivity C-Reactive Protein with Arterial Stiffness in Chinese Population: A 12-Year Longitudinal Study.

BACKGROUND: Elevated plasma homocysteine (Hcy) and high-sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular diseases. However, it is unclear whether the coexistence of these conditions accelerates the risk of arterial stiffness. Our study aimed to evaluate the association of combined Hcy and hsCRP with arterial stiffness in Chinese middle-aged adults. MATERIAL/METHODS: We conducted a 12-year longitudinal study in 220 individuals in Hanzhong, China, from 2005 to 2017. The average age at follow-up was 41.83 ± 3.10 years. Demographic information, medical history, anthropometric measurements, and blood pressure as well as urine and fasting blood samples, including Hcy, hsCRP, and brachial-ankle pulse wave velocity (baPWV) were measured and analyzed. RESULTS: BaPWV levels showed a linear growth trend with the increasing of hsCRP (p for trend <0.01). The ORs in the highest quartile compared to the lowest quartile were 1.985 (95% CI 0.776-5.077; p = 0.152) and 3.960 (95% CI 1.468-10.684; p= 0.007) for Hcy and hsCRP, respectively. When Hcy and hsCRP were combined, subjects in both the highest quartile of Hcy and hsCRP (Hcy ≥15.50 µmol/L and hsCRP ≥0.82 µmol/L) had a 12.68-fold increased risk of developing arterial stiffness at the 12-year follow-up compared to those in the lowest quartile of Hcy and hsCRP (Hcy ≤9.91 µmol/L and hsCRP ≤0.19 µmol/L) after adjusting for potential confounders. CONCLUSIONS: The present study demonstrated that the combination of elevated serum Hcy and hsCRP may contribute to an increased risk of arterial stiffness.

Establishing and validating of an laboratory information system-based auto-verification system for biochemical test results in cancer patients.

BACKGROUND: To establish and validate an laboratory information system (LIS)-based auto-verification (AV) system by using large amounts of biochemical test results in cancer patients. METHODS: An algorithm of the AV process was designed for pre-analysis, analysis, and post-analysis. The limit range check was adjusted three times, while the delta check criteria were first replaced by the same patients' historical extremum results. AV rules of 51 biochemical test items were tested by using data of 121 123 samples (6 177 273 tests) in 2016 that were manually reviewed through the simulative i-Vertification software of Roche. The improved and optimal AV rules were programed into our LIS and validated by using 140 113 clinical specimens in 2018. RESULTS: The AV passing rate for samples tested in our laboratory increased from 15.57% to the current overall passing rate of 49.70%. The passing rate of each item for rule 3 was between 71.16% and 99.91%. Different cancer groups had different passing rate, while the disease group of liver, gallbladder, and pancreas always had the lowest passing rate. A total of 9420 reports (6.72%) were not verified by AV but could be verified by MV in 2018, while there were no reports that were verified by AV but not by MV. The TAT of March 2018 decreased with increase in sample size compared with the same time in 2017. CONCLUSION: We have firstly established an LIS-based AV system and implemented it in actual clinical care for cancer patients.

Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age.

BACKGROUND: Although high BP is one of the most important factors affecting renal function, whether longitudinal BP trajectories in early life course are associated with renal function damage in later life is unclear. METHODS: To investigate the correlation between BP trajectories from childhood to adulthood and renal function in middle age, we used group-based trajectory models to identify BP trajectories in 2430 individuals (aged 6-15 years old at baseline) participating in the ongoing Hanzhong Adolescent Hypertension Cohort. We tested the association between these trajectories and subclinical renal damage in middle age, adjusting for several covariates. RESULTS: We identified four distinct systolic BP trajectories among 2430 subjects: low stable, moderate stable, high stable, and moderate increasing on the basis of systolic BP levels at baseline and during the 30-year follow-up period. The urinary albumin-to-creatinine ratio (uACR) was higher in moderate stable, high stable, and moderate increasing groups compared with the low stable group. A total of 228 individuals had subclinical renal disease by 2017. Compared with the low stable trajectory group, the other groups had increasingly greater odds of experiencing subclinical renal disease in middle age. These associations were not altered after adjustment for other covariates, except for in the moderate stable group. Analyzed results were similar for the mean arterial pressure and diastolic BP trajectory groups. CONCLUSIONS: Higher BP trajectories were correlated with higher of uACR levels and risk of subclinical renal disease in middle age. Identifying long-term BP trajectories from early age may assist in predicting individuals' renal function in later life.

Involvement of NLRP3 inflammasome in the impacts of sodium and potassium on insulin resistance in normotensive Asians.

Salt, promoting oxidative stress, contributes to insulin resistance, whereas K, inhibiting oxidative stress, improves insulin sensitivity. Oxidative stress activation of NLRP3 inflammasome is a central player in the induction of insulin resistance. Therefore, we hypothesised that NLRP3 inflammasome may mediate the effects of salt and K on insulin resistance. In all, fifty normotensive subjects were recruited from a rural community of Northern China. The protocol included a low-salt diet for 7 d, then a high-salt diet for 7 d and a high-salt diet with K supplementation for another 7 d. In addition, THP-1 cells were cultured in different levels of Na with and without K. The results showed that salt loading elevated fasting blood glucose, insulin and C-peptide levels, as well as insulin resistance, whereas K supplementation reversed them. Meanwhile, additional K reversed the active effects of high salt on NLRP3 inflammasome in both the subjects and THP-1 cells, and the change of insulin resistance index notably related with the alteration of plasma IL-1ß, the index of NLRP3 inflammasome activation, during intervention in the subjects. Additional K ameliorated oxidative stress induced by high salt in both the subjects and cultured THP-1 cells, and the change of oxidative stress related with the alteration of plasma IL-1ß during intervention in the subjects. In vitro, antioxidant N-acetyl-l-cysteine significantly prevented the active effects of high Na or oxidant Rosup on NLRP3 inflammasome, so did K. Our study indicates that oxidative stress modulation of NLRP3 inflammasome may be involved in the impacts of Na and K on insulin resistance.

The Relationships of the Fractional Excretion of Uric Acid with Brachial-Ankle Pulse Wave Velocity and Ankle Brachial Index in Chinese Young Adults.

BACKGROUND/AIMS: Elevated serum uric acid (UA) was intimately correlated with vascular stiffness and abnormal ankle brachial index (ABI) in various populations. These correlations lost significance after adjustment for estimated glomerular filtration rate (eGFR), indicating that the association of UA and brachial-ankle pulse wave velocity (baPWV) or ABI might be driven by kidney function. UA is predominantly eliminated through the kidneys, and metabolic disorders can influence the clearance of UA. In this study, we aimed to explore the putative correlation between FEUA and baPWV or ABI to determine to what extent the associations with UA were affected by renal function. METHODS: This cross-sectional study enrolled 2351 participants, who underwent general health screening in Hanzhong people's hospital from March to June of 2017. BaPWV and ABI were measured using a volume-plethysmographic apparatus (BP-203RPEII; Nihon Colin, Tokyo, Japan). FEUA was divided into quartiles: Q1:FEUA≤3.07; Q2: 3.07 9.19. RESULTS: Lower FEUA predicted a higher prevalence of high baPWV and low ABI (p for trend <0.001). The respective ORs for high baPWV from the first to the third quartiles of FEUA were 1.777(1.323, 2.387); 1.561(1.158, 2.104); and 1.680 (1.250, 2.259). The prevalence of low ABI was greatly elevated with the decrement of FEUA [ORs for the first to third FEUA quartiles were 6.977(2.062, 23.610); 5.123(1.475, 17.790); and 2.685(0.709, 10.171), respectively]. The association of FEUA and ABI was independent of related confounding factors. However, the association between FEUA and baPWV was greatly influenced by corresponding confounders, especially gender. The efficacy of FEUA in the prediction of low ABI was stronger than that of serum UA. However, serum UA was more powerful in the prediction of high baPWV. CONCLUSION: Kidney function exerted a profound influence on the relationship between UA and baPWV or ABI, revealing complex interactions among cardiovascular risk factors.