Multifaceted Intensive Blood Pressure Control Model in Older and Younger Individuals With Hypertension: A Randomized Clinical Trial.

Importance: The sustainable effectiveness and safety of a nonphysician community health care practitioner-led intensive blood pressure intervention on cardiovascular disease have not, to the authors' knowledge, been studied, especially in the older adult population. Objective: To evaluate such a multifaceted model with a more stringent blood pressure treatment goal (<130/80 mm Hg) among patients aged 60 years and older with hypertension. Design, Setting, and Participants: This was a 48-month follow-up study of the China Rural Hypertension Control Project (CRHCP), an open-cluster randomized clinical trial, conducted from 2018 to 2023. Participants 60 years and older and younger than 60 years with a diagnosis of hypertension from the CRHCP trial were included for analysis. Individuals were recruited from 326 villages in rural China. Interventions: The well-trained, nonphysician, community health care practitioner implemented a multifaceted intervention program (eg, initiation or titration of antihypertensive medications) to achieve a blood pressure level of less than 130/80 mm Hg, supervised by primary care physicians. Main Outcomes and Measures: Cardiovascular disease (a composite of myocardial infarction, stroke, heart failure requiring hospitalization, and cardiovascular disease death). Results: A total of 22 386 individuals 60 years and older with hypertension and 11 609 individuals younger than 60 years with hypertension were included in the analysis. The mean (SD) age of the participants was 63.0 (9.0) years and included 20 825 females (61.3%). Among the older individuals with hypertension, a total of 11 289 patients were randomly assigned to the intervention group and 11 097 to the usual-care group. During a median (IQR) of 4.0 (4.0-4.1) years, there was a significantly lower rate of total cardiovascular disease (1133 [2.7%] vs 1433 [3.5%] per year; hazard ratio [HR], 0.75; 95% CI, 0.69-0.81; P < .001) and all-cause mortality (1111 [2.5%] vs 1210 [2.8%] per year; HR, 0.90; 95% CI, 0.83-0.98; P = .01) in the intervention group than in the usual-care group. For patients younger than 60 years, the risk reductions were also significant for total cardiovascular disease (HR, 0.64; 95% CI, 0.56-0.75; P < .001), stroke (HR, 0.64; 95% CI, 0.55-0.76; P < .001), heart failure (HR, 0.39; 95% CI, 0.18-0.87; P = .02), and cardiovascular death (HR, 0.54; 95% CI, 0.37-0.77; P < .001), with all interaction P values for age groups greater than .05. In both age categories, the incidences of injurious falls, symptomatic hypotension, syncope, and the results for kidney outcomes did not differ significantly between groups. Conclusions and Relevance: In both the aging and younger general population with hypertension, the nonphysician health care practitioner-led, multifaceted, intensive blood pressure intervention model could effectively and safely reduce the risk of cardiovascular disease and all-cause death. Trial Registration: ClinicalTrials.gov Identifier: NCT03527719.

Impact of baseline cardiovascular risk on the outcomes of intensive blood pressure intervention: a post hoc analysis of the China rural hypertension control project.

BACKGROUND: The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). METHODS: This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths. RESULTS: Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There's no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles. CONCLUSIONS: Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT03527719.

Associations of sleep duration, daytime napping, and snoring with depression in rural China: a cross-sectional study.

BACKGROUND: Most adult patients with depression complain about sleep symptoms, including insufficient and excessive sleep. However, previous studies investigating the impact of sleep duration on depression have yielded conflicting results. Therefore, this study aimed to analyse the link between depression and sleep duration, daytime napping, and snoring among rural Chinese adults. METHODS: A cross-sectional study was conducted with 9104 individuals. Interviews were conducted with the participants regarding their sleep patterns and their daytime napping routines. The individuals were then assessed for depression using the Patient Health Questionnaire-9. The risk of depression was assessed using a multifactor binary logistic regression analysis. A generalized additive model was used to evaluate the nonlinear relationship between depression and sleep duration/nap time. Additionally, subgroup analysis was conducted to investigate the correlation between sleep duration, daytime napping, snoring, and depression. RESULTS: Less than 6 h or more than 8 h of nighttime sleep, daytime napping for more than 1 h, and snoring were all significantly associated with an increased risk of depression. A U-shaped relationship was found between the duration of nighttime sleep and depression. In addition, we found that the nighttime duration of sleep, daytime naps, and snoring had a significant combined effect on the risk of depression. The subgroup analysis further revealed that lack of sleep at night significantly increased the risk of depression in all subgroups. However, snoring and excessive nighttime sleep and napping were only associated with the risk of depression in some subgroups. CONCLUSIONS: Lack of nighttime sleep (short sleep duration), excessive sleep, and napping for more than one hour during the day were associated with a high risk of depression and had a combined effect with snoring.

Comparing the performance of machine learning and conventional models for predicting atherosclerotic cardiovascular disease in a general Chinese population.

BACKGROUND: Accurately predicting the risk of atherosclerotic cardiovascular disease (ASCVD) is crucial for implementing individualized prevention strategies and improving patient outcomes. Our objective is to develop machine learning (ML)-based models for predicting ASCVD risk in a prospective Chinese population and compare their performance with conventional regression models. METHODS: A hybrid dataset consisting of 551 features was used, including 98 demographic, behavioral, and psychological features, 444 Electrocardiograph (ECG) features, and 9 Echocardiography (Echo) features. Seven machine learning (ML)-based models were trained, validated, and tested after selecting the 30 most informative features. We compared the discrimination, calibration, net benefit, and net reclassification improvement (NRI) of the ML models with those of conventional ASCVD risk calculators, such as the Pooled Cohort Equations (PCE) and Prediction for ASCVD Risk in China (China-PAR). RESULTS: The study included 9,609 participants (mean age 53.4 ± 10.4 years, 53.7% female), and during a median follow-up of 4.7 years, 431 (4.5%) participants developed ASCVD. In the testing set, the final ML-based ANN model outperformed PCE, China-PAR, recalibrated PCE, and recalibrated China-PAR in predicting ASCVD. This was demonstrated by the model's higher area under the curve (AUC) of 0.800, compared to 0.777, 0.780, 0.779, and 0.779 for the other models, respectively. Additionally, the model had a lower Hosmer-Lemeshow χ2 of 9.1, compared to 37.3, 67.6, 126.6, and 18.6 for the other models. The net benefit at a threshold of 5% was also higher for the ML-based ANN model at 0.017, compared to 0.016, 0.013, 0.017, and 0.016 for the other models, respectively. Furthermore, the NRI was 0.089 for the ML-based ANN model, while it was 0.355, 0.098, and 0.088 for PCE, China-PAR, and recalibrated PCE, respectively. CONCLUSIONS: Compared to conventional regression ASCVD risk calculators, such as PCE and China-PAR, the ANN prediction model may help optimize identification of individuals at heightened cardiovascular risk by flexibly incorporating a wider range of potential predictors. The findings may help guide clinical decision-making and ultimately contribute to ASCVD prevention and management.

Comparison of conventional and unconventional obesity indices associated with new-onset hypertension in different sex and age populations.

We aimed to compare the relationship between hypertension and obesity-related anthropometric indices (waist circumference [WC], waist-height ratio, waist-hip ratio [WHR], and body mass index; unconventional: new body shape index [ABSI] and body roundness index [BRI]) to identify best predictors of new-onset hypertension. The study included 4123 adult participants (2377 women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using a Cox regression model to estimate the risk of new-onset hypertension with respect to each obesity index. In addition, we assessed the predictive value of each obesity index for new-onset hypertension using area under the receiver operating characteristic curve (AUC) after adjusting for common risk factors. During the median follow-up of 2.59 years, 818 (19.8%) new hypertension cases were diagnosed. The non-traditional obesity indices BRI and ABSI had predictive value for new-onset hypertension; however, they were not better than the traditional indexes. WHR was the best predictor of new-onset hypertension in women aged ≤ 60 and > 60 years, with HRs of 2.38 and 2.51 and AUCs of 0.793 and 0.716. However, WHR (HR 2.28, AUC = 0.759) and WC (HR 3.24, AUC = 0.788) were the best indexes for predicting new-onset hypertension in men aged ≤ 60 and > 60 years, respectively.

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.

Use of the Vascular Overload Index to Predict Cardiovascular Disease in a Rural Population of China.

Objective: To explore the relationship between vascular overload index (VOI) and cardiovascular disease (CVD) in rural population and find effective ways to prevent cardiovascular disease in rural low-income populations. Methods: The data for this study was obtained from a large cohort study called the Northeast China Rural Cardiovascular Health Study (NCRCHS) conducted in 2013 and followed up during 2015-2018. 10,174 subjects completed at least one follow-up visit. Cox regression equation was used to explore whether VOI and cardiovascular disease were independently related. The Kaplan-Meier curves were used to calculate the cumulative incidence of any adverse outcome, and the log-rank test and restrict mean survival analysis were used to compare group differences. Reclassification and discrimination statistics were used to determine whether VOI could strengthen the ability of the model to predict CVD events. Results: The prevalence of CVD in the VOI quartiles was 1.92%, 3.96%, 5.42%, and 11.34% for Q1-Q4, respectively (P for trend <0.001). After adjusting for multiple confounders, there was a 2.466-fold increased risk of CVD when comparing the highest and lowest groups. Besides, this study found that for every standard deviation increase, the results still exist. The risk of cardiovascular disease increased by 1.358-fold in this model. The restrict mean survival analysis results show that with the increase of VOI, the restrict mean survival time (RMST) within 5 years gradually became shorter. Reclassification and discrimination statistics indicated that VOI significantly enhanced the ability to estimate CVD events within 4 years. Conclusion: Analyses showed that VOI was significantly associated with CVD. VOI is a simple and accurate prognostic marker of CVD risk, which has the potential ability to improve the risk stratification of CVD.

Combined superposition effect of hypertension and dyslipidemia on left ventricular hypertrophy.

BACKGROUND: Hypertension and dyslipidemia are considered reversible risk factors for cardiovascular disease. The purpose of this study was to explore the impact of traditional and nontraditional blood lipid profiles on the risk of left ventricular hypertrophy (LVH) and to explore the superposition effect of dyslipidemia combined with hypertension. METHODS: Data on 9134 participants (53.5 ± 10.3 years old) from the Northeast China Rural Cardiovascular Health Study (NCRCHS) were statistically analyzed. The blood lipid profile was measured by total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total glyceride (TG), and calculated nontraditional blood lipid indices including non-HDL-C, atherosclerosis index (AI), TC/HDL-C, and residual cholesterol (RC). RESULTS: After the adjustment of age and gender, the odds ratios (ORs) of LVH in patients with hypertension, high LDL-C, high non-HDL-C, high AI, and high TC/HDL-C were 3.97 (3.31-4.76), 1.27 (1.02-1.59), 1.21 (1.04-1.39), 1.33 (1.15-1.53), and 1.42 (1.22-1.65), respectively. After full adjustment of potential confounding factors, high AI and TC/HDL-C were associated with LVH rather than traditional blood lipid indices. The combination of hypertension and nontraditional dyslipidemia (defined by high AI and TC/HDL-C) was associated with the highest risk of LVH, especially in participants under 45 years of age. The risk was more significant in men, 5.09-fold and 6.24-fold, respectively, compared with 3.66-fold and 4.01-fold in women. CONCLUSIONS: People with dyslipidemia defined by nontraditional blood lipid indices (high AI and high TC/HDL-C) and hypertension were more likely to develop LVH.

Hyperlipidemia and hypertension have synergistic interaction on ischemic stroke: insights from a general population survey in China.

BACKGROUND: Hyperlipidemia (HLP) and hypertension (HTN) are both independent risk factors for ischemic stroke. This study aimed to assess whether HTN and HLP have a synergistic effect on the risk of ischemic stroke. METHODS: Between January and August 2013, 11,695 subjects in rural areas of northeastern China were enrolled. The additive and multiplicative scales were used to evaluate the interaction. RESULTS: The prevalence of ischemic stroke was 5.7%. Using the healthy group (without HTN or HLP) as the reference group, subjects with both HTN and HLP had a higher risk of ischemic stroke (odds ratio [OR]: 3.369, 95% confidence interval [CI]: 2.579-4.402), and this OR was greater than that of subjects with only HTN (OR: 1.995, 95% CI 1.526-2.610) or HLP (OR: 1.321, 95% CI 0.937-1.862) (adjusting for age, sex, race, education level, family income, current smoking and drinking status, physical activity, body mass index, diabetes, family history of stroke, and atrial fibrillation). Regarding the additive scale, the relative excess risk due to interaction (OR: 1.053, 95% CI 0.458-1.648) was positive after adjusting for confounders. Moreover, the attributable proportion was 31.3%, which means that 31.3% of the total risk of ischemic stroke was due to the synergistic interaction between HTN and HLP. Furthermore, the synergistic index (S) of ischemic stroke was 1.8 (95% CI 1.157-2.801), which also indicates a synergistic interaction between HTN and HLP. Regarding the multiplicative scale, the interaction effect was also significant after adjusting for confounders (OR: 2.163, 95% CI 1.817-2.575). CONCLUSION: The results suggest that the synergistic effect of HTN and HLP on ischemic stroke is significantly higher than the sum of their independent effects. The quantification of the combined effect should help to promote healthy blood pressure and blood lipid levels among the general population.

An unexpected role for BAG3 in regulating PARP1 ubiquitination in oxidative stress-related endothelial damage.

Oxidative stress-associated endothelial damage is the initiation factor of cardiovascular disease, and protein posttranslational modifications play critical roles in this process. Bcl-2-associated athanogene 3 (BAG3) is a molecular chaperone regulator of the BAG family, which interacts with various proteins and influences cell survival by activating multiple pathways. BAG3 undergoes posttranslational modifications; however, research evaluating BAG3 acetylation and its regulatory mechanism is lacking. In addition, the interacting protein and regulatory mechanism of BAG3 in oxidative stress-associated endothelial damage remain unclear. Here, key molecular interactions and protein modifications of BAG3 were identified in oxidative stress-associated endothelial damage. Endothelial-specific BAG3 knockout in the mouse model starkly enhances oxidative stress-associated endothelial damage and vascular remodeling, while BAG3 overexpression in mice significantly relieves this process. Mechanistically, poly(ADP-ribose) polymerase 1 (PARP1), causing oxidative stress, was identified as a novel physiological substrate of BAG3. Indeed, BAG3 binds to PARP1's BRCT domain to promote its ubiquitination (K249 residue) by enhancing the E3 ubiquitin ligase WWP2, which leads to proteasome-induced PARP1 degradation. Furthermore, we surprisingly found that BAG3 represents a new substrate of the acetyltransferase CREB-binding protein (CBP) and the deacetylase Sirtuin 2 (SIRT2) under physiological conditions. CBP/SIRT2 interacted with BAG3 and acetylated/deacetylated BAG3's K431 residue. Finally, deacetylated BAG3 promoted the ubiquitination of PARP1. This work reveals a novel regulatory system, with deacetylation-dependent regulation of BAG3 promoting PARP1 ubiquitination and degradation via enhancing WWP2, which is one possible mechanism to decrease vulnerability of oxidative stress in endothelial cells.

A nomogram integrating non-ECG factors with ECG to screen left ventricular hypertrophy among hypertensive patients from northern China.

OBJECTIVE: We aimed to establish and validate a user-friendly and clinically practical nomogram for estimating the probability of echocardiographic left ventricular hypertrophy (echo-LVH) indexed to BSA among hypertensive patients from northern China. METHODS: A total of 4954 hypertensive patients were recruited from a population-based cohort study from January 2012 to August 2013. The dataset was randomly split into two sets: training (n = 3303) and validation (n = 1651). Three nomograms were initially constructed. That is the Cornell product nomogram, the non-ECG nomogram, and the integrated nomogram which integrated non-ECG risk factors and Cornell-voltage duration product. The least absolute shrinkage and selection operator strategies were employed to screen for non-ECG features. The performance of the nomograms was evaluated using discrimination, calibration, and decision curve analysis (DCA). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also calculated. RESULTS: The AUCs, NRIs, IDIs, and DCA curves of the nomograms demonstrated that the integrated nomogram performed best among all three nomograms. The integrated nomogram incorporated age, sex, educational level, hypertension duration, SBP, DBP, eGFR, sleep duration, tea consumption, and the Cornell-voltage duration product. The AUC was 0.758 and had a good calibration (Hosmer-Lemeshow test, P = 0.73). Internal validation showed an acceptable AUC of 0.735 and good calibration was preserved (Hosmer-Lemeshow test, P = 0.19). The integrated nomogram was clinically beneficial across a range of thresholds of 10-50%. CONCLUSION: The integrated nomogram is a convenient and reliable tool that enables early identification of hypertensive patients at high odds of LVH and can assist clinicians in their decision-making.

Risk factor control after ischemic stroke or transient ischemic attack.

OBJECTIVE: We aimed to estimate the status of risk factor control after ischemic stroke or transient ischemic attack (IS/TIA), and the influence on recurrent stroke in rural communities of northeastern China. METHODS: This population-based, prospective cohort study enrolled adults aged ≥35 years residing in rural northeastern China. We conducted cardiovascular health examinations in 2012-2015 and followed up in 2018 to record any cardiovascular event. Control of risk factors after IS/TIA was determined through a baseline survey. The Cox proportional hazard model was used to evaluate the relationship between uncontrolled risk factors and stroke recurrence. RESULTS: Of the 10,700 participants, 575 were diagnosed with IS/TIA and were included in the analysis. At baseline, the rates of control of risk factors were as follows: fasting plasma glucose (FPG), 81.6%; not currently smoking, 65.7%; and achieving physical activity targets, 61%. Blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI) were poorly controlled (28.3%, 26.3%, and 37.4%, respectively). The rate of stroke recurrence was 12% during a median follow-up of 4.43 years. After adjusting for age, sex, ethnicity, family history of stroke, and current drinking, uncontrolled BP and not achieving physical exercise targets were associated with an increased risk of recurrence (hazard ratios: 2.081, 1.685, respectively; p < .05). Uncontrolled FPG, BMI, or LDL-C and current smoking did not significantly influence recurrent risk (p > .05). CONCLUSIONS: Control of risk factors after IS/TIA needs to be improved in rural communities of northeastern China to prevent recurrence and thus alleviate the public health and economic burden of stroke.

Impact of monocyte to high-density lipoprotein ratio on prevalent hyperuricemia: findings from a rural Chinese population.

BACKGROUND: Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammatory marker that has been used to predict various inflammation-related diseases. This study aims to explore the association between MHR and prevalent hyperuricemia in a rural Chinese population. METHODS: 8163 eligible participants (mean age: 54.13 years, males: 45.71%) from northeast China were enrolled in this cross-sectional study between 2012 to 2013. MHR was determined as blood monocyte count ratio to high-density lipoprotein cholesterol concentration. RESULTS: The prevalence of hyperuricemia was 12.86%. After adjusting for potential confounding factors, per SD increase of MHR caused a 25.2% additional risk for hyperuricemia, and the top quartile of MHR had an 82.9% increased risk for hyperuricemia compared with the bottom quartile. Additionally, smooth curve fitting and subgroup analyses showed a linear and robust association between MHR and prevalent hyperuricemia respectively. Finally, after introducing MHR into the established model of risk factors, the AUC displayed a significant improvement (0.718 vs 0.724, p = 0.008). Furthermore, Category-free net reclassification improvement (0.160, 95% CI: 0.096-0.224, P < 0.001) and integrated discrimination improvement (0.003, 95% CI: 0.002-0.005, P < 0.001) also demonstrated significant improvements. CONCLUSIONS: The present study suggests that MHR was positively and independently correlated with prevalent hyperuricemia among rural Chinese adults. Our results also implicate an important value for MHR in optimizing the risk stratification of hyperuricemia.