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.

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.

Plasma Renalase is Not Associated with Blood Pressure and Brachial-Ankle Pulse Wave Velocity in Chinese Adults With Normal Renal Function.

BACKGROUND/AIMS: This study aimed to investigate the association of renalase with blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) in order to better understand the role of renalase in the pathogenesis of hypertension and atherosclerosis. METHODS: A total of 344 subjects with normal kidney function were recruited from our previously established cohort in Shaanxi Province, China. They were divided into the normotensive (NT) and hypertensive (HT) groups or high baPWV and normal baPWV on the basis of BP levels or baPWV measured with an automatic waveform analyzer. Plasma renalase was determined through an enzyme-linked immunosorbent assay. RESULTS: Plasma renalase did not significantly differ between HT and NT groups (3.71 ± 0.69 µg/mL vs. 3.72 ± 0.73 µg/mL, P = 0.905) and between subjects with and without high baPWV (3.67 ± 0.66 µg/mL vs. 3.73 ± 0.74 µg/mL, P = 0.505). However, baPWV was significantly higher in the HT group than in the NT group (1460.4 ± 236.7 vs. 1240.7 ± 174.5 cm/s, P < 0.001). Plasma renalase was not correlated with BP levels and baPWV in the entire group. Linear and logistic regression analysis revealed that plasma renalase was not significantly associated with hypertension and high baPWV. CONCLUSION: Plasma renalase may not be associated with BP and baPWV in Chinese subjects with normal renal function.

[Relationship between female menopause and hypertension/isolated systolic hypertension in rural districts of Hanzhong in Shaanxi province].

OBJECTIVE: To analyze the associations between menopause and hypertension/isolated systolic hypertension (ISH) among rural females in Hanzhong, Shaanxi Province, China. METHODS: In this cross-sectional study, 3030 residents were selected by stratified random sampling and investigated by questionnaire survey and physical examinations. Data of the females were analyzed to explore the impact of menopause on blood pressure by quantile regression and to investigate the associations between menopause and hypertension, ISH, and isolated distolic hypertension (IDH) by logistic regression. RESULTS: The number of premenopausal and postmenopausal women was 965 and 998. The average age was (41.0 ± 8.07) years in the premenopausal group and (58.0±7.12) years in the postmenopausal group (P<0.001). The prevalence of hypertension among the premenopausal group and postmenopausal group was 21.9% and 49.3%, respectively. Quantiles regression analysis showed that the impact of menopause on systolic blood pressure increased as the percentile increased. The diastolic blood pressure (DBP) of the premenopausal group was significantly lower than that in the postmenopausal at q ≥ 0.40(DBP = 84 mmHg,1 mmHg = 0.133 kPa) percentile points (P<0.05), while the difference was not significant at q≤ 0.30 (DBP=80 mmHg) percentile points(P>0.05). After the potential confounders including age, education level, marriage, occupational, hyperlipidemia, family history, exercise, sleep, watching TV, smoking, passive smoking, alcohol consumption, body mass index, wealth index, waist circumference were controlled, positive associations were observed between menopause and hypertension/ISH in logistic regression models. CONCLUSIONS: Menopause is positively related with hypertension/ISH. More effective interventions should be taken to prevent hypertension and ISH among rural women.

[Survey on the prevalences of overweight and obesity in 9 rural areas in Hanzhong, Shaanxi province].

OBJECTIVE: To investigate the prevalences of overweight and obesity in the rural communities in Hanzhong, Shaanxi Province. METHODS: A total of 3030 residents in the rural areas of Hanzhong city were selected by stratified random sampling method to take questionnaire-based survey and physical examinations. RESULTS: The data of 3017 valid subjects (1048 men and 1969 women) entered the final analysis. The average body mass index was (22.9±4.2) kg/m(2) [(23.0±5.5) kg/m(2) in men and (22.9±3.2) kg/m(2) in women]. The prevalence rates of overweight and obesity were 27.9% and 5.9% respectively, and the standardized rates were 23.4% and 5.4%, respectively. More specifically, prevalence rates of overweight and obesity were 28.3% and 6.1% in men (standardized rates were 24.7% and 7.5%, respectively) and 27.6% and 5.8% (standardized rate were 22.8% and 4.5% respectively) in women. The overweight/obesity was more often in young and mid-aged married men with higher education and socioeconomic status and in middle-aged and older women with less education from wealthier households. CONCLUSION: The prevalences of overweight and obesity are relatively high in the rural areas of Hanzhong, and therefore effective interventions are warranted.

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

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

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

BACKGROUND: Data on the association of isolated diastolic hypertension (IDH) in childhood with adult cardiovascular risk are scarce. This study aimed to estimate the prevalence of IDH in adolescents and to explore the impact of IDH in childhood on adult subclinical target organ damage (STOD). METHODS: This longitudinal study consisted of 1738 school children (55.4% boys) aged 6-15 years from rural areas of Hanzhong, Shaanxi, who were followed for 30 years. Their blood pressure was recorded to define the hypertension subtypes: normotension, IDH, isolated systolic hypertension (ISH) and mixed hypertension. Tracked STOD included arterial stiffness ( n  = 1738), albuminuria ( n  = 1652) and left ventricular hypertrophy (LVH) ( n  = 1429). RESULTS: Overall, the prevalence of IDH, ISH and mixed hypertension was 5.4, 2.2 and 3%, respectively, and there was no gender difference. Over 30 years, 366 (21.1%) of participants developed arterial stiffness, 170 (10.3%) developed albuminuria and 68 (4.8%) developed LVH. Compared with normotensive participants, IDH in childhood had higher risk ratio (RR) of experiencing arterial stiffness (RR, 1.66; 95% CI, 1.01-2.76) and albuminuria (RR, 2.27; 95% CI, 1.35-4.16) in adults after being fully adjusted but not LVH. However, if the elevated blood pressure in children was used as the reference standard, IDH in childhood was associated with adult LVH (RR, 2.48; 95% CI, 1.28-4.84). CONCLUSION: IDH accounts for a higher proportion of adolescent hypertension subtypes and can increase the risk of adult STOD. These results highlight the necessity of improving the prevention, detection and treatment of IDH in adolescents.

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.

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

The pulsatile stress in the microcirculation may contribute to development or progression of chronic kidney disease. However, there is no prospective data confirming whether pulsatile stress in early life affect renal function in middle age. The authors performed a longitudinal analysis of 1738 participants aged 6-15 years at baseline, an ongoing Adolescent Prospective Cohort with a follow-up of 30 years. The authors evaluated the association between pulsatile stress in childhood and adult subclinical renal damage (SRD), adjusting for related covariates. Pulsatile stress was calculated as resting heart rate × pulse pressure. Renal function was assessed with estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR). The results showed that pulsatile stress in childhood was associated with adult SRD (Relative Risk, 1.43; p = .032), and the predictive value of combined pulse pressure and heart rate for SRD was higher than either of them alone. The high pulsatile stress in childhood increased the risk of adult SRD in males (RR, 1.92; p = .003), but this association was not found in females (RR, 0.91; p = .729). Further, the participants were categorized into four groups on the basis of pulsatile stress status in childhood and adulthood. Male patients with high pulsatile stress during childhood but normal pulsatile stress as adults still had an increased risk of SRD (RR, 2.04; 95% CI, 1.18-3.54), while female patients did not (RR, 0.96; 95% CI, 0.46-1.99). The study demonstrated that high pulsatile stress in childhood significantly increased the risk of adult SRD, especially in males. Adequate control of pulse pressure and heart rate from childhood, in the long-term, is very important for preventing kidney damage.