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.

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.

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 role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.

Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable disease deaths. Glycolysis is a conserved and rigorous biological process that breaks down glucose into pyruvate, and its primary function is to provide the body with the energy and intermediate products needed for life activities. The non-glycolytic actions of enzymes associated with the glycolytic pathway have long been found to be associated with the development of CVD, typically exemplified by metabolic remodeling in heart failure, which is a condition in which the heart exhibits a rapid adaptive response to hypoxic and hypoxic conditions, occurring early in the course of heart failure. It is mainly characterized by a decrease in oxidative phosphorylation and a rise in the glycolytic pathway, and the rise in glycolysis is considered a hallmark of metabolic remodeling. In addition to this, the glycolytic metabolic pathway is the main source of energy for cardiomyocytes during ischemia-reperfusion. Not only that, the auxiliary pathways of glycolysis, such as the polyol pathway, hexosamine pathway, and pentose phosphate pathway, are also closely related to CVD. Therefore, targeting glycolysis is very attractive for therapeutic intervention in CVD. However, the relationship between glycolytic pathway and CVD is very complex, and some preclinical studies have confirmed that targeting glycolysis does have a certain degree of efficacy, but its specific role in the development of CVD has yet to be explored. This article aims to summarize the current knowledge regarding the glycolytic pathway and its key enzymes (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) for their role in cardiovascular diseases (e.g., heart failure, myocardial infarction, atherosclerosis) and possible emerging therapeutic targets.

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.

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.

Construction of a risk assessment model of cardiovascular disease in a rural Chinese hypertensive population based on lasso-Cox analysis.

Many assessments have been used to predict cardiovascular risks in the general population, but their applicability in patients with hypertension needs to be further evaluated. In the current study, a cardiovascular risk assessment model was constructed in a hypertensive population. This prospective cohort study was conducted with cardiovascular examinations in rural northeast China in 2012 and 2013, and followed up to collect cardiovascular events in 2015 and 2018. Data were derived from 4763 hypertensive patients who were free of cardiovascular disease (CVD) at baseline and completed follow-up. After lasso regression was used to screen for risk factors of CVD at baseline, a multivariate Cox regression risk model was established and a nomogram was developed. The model was validated using an independent test set (one third of data not used for model building). Among 4763 patients, 354 (7.43%) had a cardiovascular event during a median follow-up of 4.66 years. Nine risk factors were screened by lasso regression, including sex, age, current smoking, body mass index (BMI), history of transient ischemic attack (TIA), family history of hypertension, family history of stroke, physical labor intensity, and high low-density lipoprotein cholesterol (LDL-C). The c-index of the CVD model was 0.707, and that of an updated model with baseline blood pressure was 0.732. In the validated cohort the respective c-indexes were 0.665 and 0.714. An assessment model of CVD risk was established in a hypertensive population which may provide an original prevention strategy for hypertensive populations in rural China, and further reduce the CVD burden.

Interventricular Septum Thickness for the Prediction of Coronary Heart Disease and Myocardial Infarction in Hypertension Population: A Prospective Study.

The aim of the present study was to evaluate the prognostic value of interventricular septum thickness (IVSd) on the incidence of cardiovascular diseases. Based on the general population in Northeast China, 10,349 participants were successfully followed up for echocardiography over a median follow-up time of 4.66 years, among which 4801 were hypertensive. Coronary heart disease (CHD) and myocardial infarction (MI) incidence were followed up. Cox proportional hazards models were used to estimate the association of the baseline IVSd with adverse outcomes. IVS hypertrophy increased incident rates of CHD and MI compared with normal IVSd in the overall population and in the female sex-stratification group. In males, IVS hypertrophy had parallel increase rates of CHD (all p < 0.05). Kaplan−Meier analysis showed that IVS hypertrophy could predict CHD and MI incidence and CHD-free and MI-free survival. Multivariable Cox analysis revealed that IVS hypertrophy was correlated with CHD incidence (HR = 1.155, 95% CI = 1.155−2.861, p = 0.01) and MI incidence (HR = 2.410, 95% CI = 1.303−4.458, p = 0.005). In women, IVS hypertrophy was independently associated with CHD and MI incidence (all p < 0.05). Our prospective cohort study illustrated that IVS hypertrophy detected by echocardiography has a prognostic significance for CHD and MI. Therefore, the early detection of IVSd should be conducted to avoid adverse outcomes in further clinical practice.

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.

The Effects of Calculated Remnant-Like Particle Cholesterol on Incident Cardiovascular Disease: Insights from a General Chinese Population.

BACKGROUND: Growing evidence suggests that remnant cholesterol (RC) contributes to residual atherosclerotic cardiovascular disease (ASCVD) risk. However, the cutoff points to treat RC for reducing ASCVD are still unknown. This study aimed to investigate the relationships between RC and combined cardiovascular diseases (CVDs) in a general China cohort, with 11,956 subjects aged ≥ 35 years. METHODS: Baseline RC was estimated with the Friedewald formula for 8782 subjects. The outcome was the incidence of combined CVD, including fatal and nonfatal stroke and coronary heart disease (CHD). The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. The restricted cubic spline (RCS) model was used to evaluate the dose-response relationship between continuous RC and the natural log of HRs. RESULTS: After a median follow-up of 4.66 years, 431 CVD events occurred. In the Cox proportional models, participants with a high level of categorial RC had a significantly higher risk for combined CVD (HR: 1.37; 95% CI: 1.07-1.74) and CHD (HR: 1.63; 95% CI: 1.06-2.53), compared to those with a medium level of RC. In the stratification analyses, a high level of RC significantly increased combined CVD risk for subgroups females, age < 65 years, noncurrent smokers, noncurrent drinkers, normal weight, renal dysfunction, and no hyperuricemia. The same trends were found for CHD among subgroups males, age < 65 years, overweight, renal dysfunction, and no hyperuricemia; stroke among subgroup females. In RCS models, a significant linear association between RC and combined CVD and a nonlinear association between RC and CHD resulted. The risk of outcomes was relatively flat until 0.84 mmol/L of RC and increased rapidly afterwards, with an HR of 1.308 (1.102 to 1.553) for combined CVD and 1.411 (1.061 to 1.876) for CHD. Stratified analyses showed a significant nonlinear association between RC and CVD outcomes in the subgroup aged < 65 years or the diabetes subgroup. CONCLUSIONS: In this large-scale and long-term follow-up cohort study, participants with higher RC levels had a significantly worse prognosis, especially for the subgroup aged 35-65 years or the diabetes mellitus subgroup.

Rationale and Design of a Cluster Randomized Trial of a Village Doctor-Led Intervention on Hypertension Control in China.

BACKGROUND: In China, hypertension prevalence is high and increasing while the control rate is low, especially in rural areas. Traditionally, village doctors play an important role in infectious disease control and delivering essential health services to rural residents. We aim to test the effectiveness of a village doctor-led multifaceted intervention compared with usual care on blood pressure (BP) control and cardiovascular disease (CVD) among rural residents with hypertension in China. METHODS: In the China Rural Hypertension Control Project (CRHCP), a cluster randomized trial, 163 villages were randomly assigned to the village doctor-led intervention and 163 villages to control. A total of 33,995 individuals aged ≥40 years with an untreated BP ≥140/90 mm Hg or treated BP ≥130/80 mm Hg or with an untreated BP ≥130/80 mm Hg and a history of clinical CVD were recruited into the study. The village doctor-led multifaceted intervention is designed to overcome barriers at the healthcare system, provider, patient, and community levels. Village doctors receive training on standard BP measurement, protocol-based hypertension treatment, and health coaching. They also receive technical support and supervision from hypertension specialists/primary care physicians and performance-based financial incentives. Study participants receive health coaching on home BP monitoring, lifestyle changes, and adherence to medications. The primary outcome is BP control (<130/80 mm Hg) at 18 months in phase 1 and CVD events over 36 months in phase 2. CONCLUSIONS: The CRHCP will provide critically important data on the effectiveness, implementation, and sustainability of a hypertension control strategy in rural China for reducing the BP-related CVD burden. CLINICAL TRIALS REGISTRATION: Trial Number NCT03527719.