Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial.

BACKGROUND: Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke. METHODS: In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234. FINDINGS: Between Sept 17, 2019, and July 13, 2020, 11 255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64·6 years (SD 7·1). The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028). There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68). There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury. INTERPRETATION: For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk. FUNDING: The Ministry of Science and Technology of China and Fuwai Hospital. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Home Blood Pressure Monitoring and Its Association With Blood Pressure Control Among Hypertensive Patients With High Cardiovascular Risk in China.

Objective: Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence. Methods: This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment. Results: A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of anti-hypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11-1.72, P = 0.004). Conclusions: HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients' misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Associations of long-term fine particulate matter exposure with all-cause and cause-specific mortality: results from the ChinaHEART project.

Background: The chronic effects of fine particulate matter (PM2.5) at high concentrations remains uncertain. We aimed to examine the relationship of long-term PM2.5 exposure with all-cause and the top three causes of death (cardiovascular disease [CVD], cancer, and respiratory disease), and to analyze their concentration-response functions over a wide range of concentrations. Methods: We enrolled community residents aged 35-75 years from 2014 to 2017 from all 31 provinces of the Chinese Mainland, and followed them up until 2021. We used a long-term estimation dataset for both PM2.5 and O3 concentrations with a high spatiotemporal resolution to assess the individual exposure, and used Cox proportional hazards models to estimate the associations between PM2.5 and mortalities. Findings: We included 1,910,923 participants, whose mean age was 55.6 ± 9.8 years and 59.4% were female. A 10 µg/m3 increment in PM2.5 exposure was associated with increased risk for all-cause death (hazard ratio 1.02 [95% confidence interval 1.012-1.028]), CVD death (1.024 [1.011-1.037]), cancer death (1.037 [1.023-1.052]), and respiratory disease death (1.083 [1.049-1.117]), respectively. Long-term PM2.5 exposure nonlinearly related with all-cause, CVD, and cancer mortalities, while linearly related with respiratory disease mortality. Interpretation: The overall effects of long-term PM2.5 exposure on mortality in the high concentration settings are weaker than previous reports from settings of PM2.5 concentrations < 35 µg/m³. The distinct concentration-response relationships of CVD, cancer, and respiratory disease mortalities could facilitate targeted public health efforts to prevent death caused by air pollution. Funding: The Chinese Academy of Medical Sciences Innovation Fund for Medical Science, the National High Level Hospital Clinical Research Funding, the Ministry of Finance of China and National Health Commission of China, the 111 Project from the Ministry of Education of China.

Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study.

Background The age-related trends in the predictive ability of carotid intima-media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age-related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35-44, 45-54, 55-64, and 65-75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMTmean per SD decreased with age, from 1.27 (95% CI, 1.17-1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10-1.19) in the 65 to 75 years age group (P for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMTmean were attenuated with age, from 22.60% (95% CI, 15.56%-29.64%) in the 35 to 44 years age group to 7.00% (95% CI, -6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups. Conclusions CIMT may improve cardiovascular risk prediction in the young and middle-aged populations, rather than those aged ≥55 years.

Long-Term Trajectories of High-Sensitivity C-Reactive Protein Level Among Patients with Acute Heart Failure.

Background: Inflammation contributes to the progression of heart failure (HF). However, long-term inflammatory trajectories and their associations with outcomes in patients with acute HF remain unclear. Methods: Data was obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, and high-sensitivity C-reactive protein (hsCRP) was used to reflect the inflammatory level. Only patients who survived over 12-month and had hsCRP data at admission, 1-, and 12-month after discharge were included. The latent class trajectory modeling was used to characterize hsCRP trajectories. Multivariable Cox regression models were used to explore the association between hsCRP trajectories and following mortality. Results: Totally, 1281 patients with a median 4.77 (interquartile range [IQR]: 4.24-5.07) years follow-up were included. The median age was 64 years (IQR: 54-73 years); 453 (35.4%) were female. Four distinct inflammatory trajectories were characterized: persistently low (n = 419, 32.7%), very high-marked decrease (n = 99, 7.7%), persistently high (n = 649, 50.7%), and persistently very high (n = 114, 8.9%). Compared with the persistently low trajectory, the all-cause mortality was increased in a graded pattern in the persistently high (hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.23-2.07) and persistently very high (HR: 2.56, 95% CI: 1.83-3.70) trajectories; nevertheless, the mortality was not significantly increased in very high-marked decrease trajectory (HR: 0.94, 95% CI: 0.57-1.54). Conclusion: Four distinct inflammatory trajectories were identified among patients with acute HF who survived over 12-month. Patients with persistently high and very high trajectories had significantly higher mortality than those with the persistently low trajectory.

Rationale and design of the Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT): A multicenter open-label randomized controlled trial.

BACKGROUND: Lowering blood pressure (BP) effectively reduces the risk of cardiovascular (CV) events in high CV risk individuals. The optimal target of BP lowering among high CV risk individuals remains unclear. METHODS: The Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT) trial is a multi-center, open-label, randomized controlled trial to compare the efficacy and safety of intensive BP lowering strategy (Systolic BP target <120 mm Hg) and standard BP lowering strategy (Systolic BP target <140 mm Hg). Participants aged at least 50 years old with baseline systolic BP within 130 to 180 mm Hg at high CV risk, defined by established CV diseases or 2 major CV risk factors, were enrolled. The primary outcome is a composite CV outcome of myocardial infarction, coronary or non-coronary revascularization, hospitalization or emergency department visit from new-onset heart failure or acute decompensated heart failure, stroke, or death from CV diseases. Secondary outcomes include components of the primary composite outcome, all-cause death, a composite of the primary outcome or all-cause death, kidney outcomes, as well as cognitive outcomes. RESULTS: Despite of the interruption of COVID-19 outbreak, the ESPRIT trial successfully enrolled and randomized 11,255 participants from 116 hospitals or primary health care institutions. The mean age of the participants was 64.6 (standard deviation [SD], 7.1) years, 4,650 (41.3%) were women. Among them 28.9%, 26.9% and 38.7% had coronary heart disease, prior stroke and diabetes mellitus, respectively. COVID-19 outbreak affected the BP lowering titration process of the trial, and delayed the reach of BP target. CONCLUSIONS: The ESPRIT trial will address the important question on the optimal BP lowering target for individuals with high CV risk, and generate high quality evidence for treating millions of patients from East Asian countries.

Multi-Biomarker Points and Outcomes in Patients Hospitalized for Heart Failure: Insights From the China PEACE Prospective Heart Failure Study.

Objective: To quantitatively characterize the pattern of systemic impairment reflected by conventional biomarkers and assess how it relates to clinical outcomes and quality of life among patients hospitalized for heart failure (HF). Methods: Patients hospitalized for HF from 52 hospitals in China were enrolled between 2016 and 2018. They were divided into developing and validating cohorts; the developing cohort was used for calculating the weights of biomarkers and constructing the multi-biomarker panel, while the validating one was used for evaluating the relationship between multi-biomarker points and outcomes. In total, five conventional biomarkers reflecting various pathophysiological processes were included in the panel: N-terminal pro-B type natriuretic peptide, high-sensitivity troponin T, hemoglobin, albumin, and creatinine. The weights of the biomarkers were defined based on their relationship with cardiovascular death, and each patient had a multi-biomarker point ranging from 0 to 12. The primary clinical outcome was cardiovascular death, and the other clinical outcomes included rehospitalization for HF, all-cause death, and all-cause rehospitalization in 1-year. The quality of life was measured using Kansas City Cardiovascular Questionnaire. Multi-variable Cox proportional hazard models were used to assess the risks of clinical outcomes, and generalized linear models were used to evaluate the quality of life. Results: In total, 4,693 patients hospitalized for HF were included in this analysis; the median (interquartile range, IQR) age was 67 (57-75) years old and 1,763 (37.6%) were female. The median multi-biomarker point was 5 (IQR, 2-6). There were 18.0% of patients in the low point group (<2), 29.4% in the mid-low point group (2-4), 27.8% in the mid-high point group (5-6), and 24.7% in the high point group (>6). Compared with those in the low point group, the patients in the high point group had a significantly excess risk of cardiovascular death (adjusted hazard ratio: 5.69, 95% CI, 3.33-9.70). Furthermore, patients with higher points were also more prone to worse quality of life. Conclusion: Systemic impairment reflected by abnormal conventional biomarker values was common amongst patients hospitalized for HF and had substantially cumulative adverse influence on clinical outcomes and quality of life.

Characteristics, interventions and outcomes of patients with valvular heart disease hospitalised in China: a cross-sectional study.

OBJECTIVES: Little is known about contemporary characteristics and management of valvular heart disease (VHD) in China. This study aimed to examine the clinical characteristics, aetiology and type of VHD, interventions and in-hospital outcomes of patients with VHD hospitalised in China. METHODS: We used a two-stage random sampling design to create a nationally representative sample of patients with VHD hospitalised in 2015 in China and included adult patients with mild, moderate or severe VHD. We abstracted data from medical records, including echocardiogram reports, on patient characteristics, aetiology, type and severity of VHD, interventions and in-hospital outcomes. We weighted our findings to estimate nationally representative hospitalisations. We performed multivariable logistic regression analysis to identify factors associated with valve intervention. RESULTS: In 2015, 38 841 patients with VHD were hospitalised in 188 randomly sampled hospitals, representing 662 384 inpatients with VHD in China. We sampled 9363 patients, mean age 68.7 years (95% CI 42.2 to 95.2) and 46.8% (95% CI 45.8% to 47.8%) male, with an echocardiogram. Degenerative origin was the predominant aetiology overall (33.3%, 95% CI 32.3% to 34.3%), while rheumatic origin was the most frequent aetiology among patients with VHD as the primary diagnosis (37.4%, 95% CI 35.9% to 38.8%). Rheumatic origin was also the most common aetiology among patients with moderate or severe VHD (27.3%, 95% CI 25.6% to 29.0% and 33.6%, 95% CI 31.9% to 35.2%, respectively). The most common VHD was mitral regurgitation (79.1%, 95% CI 78.2% to 79.9%), followed by tricuspid regurgitation (77.4%, 95% CI 76.5% to 78.2%). Among patients with a primary diagnosis of severe VHD who were admitted to facilities capable of valve intervention, 35.6% (95% CI 33.1% to 38.1%) underwent valve intervention during the hospitalisation. The likelihood of intervention decreased significantly among patients with higher operative risk. CONCLUSIONS: Among patients with VHD hospitalised in China, the predominant aetiology was degenerative in origin; among patients with moderate or severe VHD, rheumatic origin was the most common aetiology. Targeted strategies and policies should be promoted to address degenerative VHD. Patients with severe VHD may be undertreated, particularly those with high operative risk.

Health Status Predicts Short- and Long-Term Risk of Composite Clinical Outcomes in Acute Heart Failure.

OBJECTIVES: This study aims to examine the association between the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score and the 30-day and 1-year rates of composite events of cardiovascular death and heart failure (HF) rehospitalization in patients with acute HF. BACKGROUND: Few studies reported the prognostic effects of KCCQ in acute HF. METHODS: This study prospectively enrolled adult patients hospitalized for HF from 52 hospitals in China and collected the KCCQ-12 score within 48 hour of index admission. The study used multivariable Cox regression to examine the association between KCCQ-12 score and 30-day and 1-year composite events and was further stratified by new-onset HF and acutely decompensated chronic heart failure (ADCHF). Subgroup analyses were performed to explore the potential heterogeneity. The study evaluated the incremental prognostic value of KCCQ-12 score over N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and established risk scores by C-statistics, net reclassification improvement, and integrated discrimination improvement. RESULTS: Among 4,898 patients, 29.4% had new-onset HF. After adjustment, each 10-point decrease in the KCCQ-12 score was associated with a 13% increase in 30-day risk and a 7% increase in 1-year risk. The associations were consistent regardless of new-onset HF or ADCHF, age, sex, left ventricular ejection fraction, New York Heart Association functional class, NT-proBNP level, comorbidities, and renal function. Adding KCCQ-12 score to NT-proBNP and established risk scores significantly improved prognostic capabilities measured by C-statistics, net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In acute HF, a poor KCCQ-12 score predicted short- and long-term risks of cardiovascular death and HF rehospitalization. KCCQ-12 could serve as a convenient tool for rapid initial risk stratification and provide additional prognostic value over NT-proBNP and established risk scores.

Serum tissue inhibitor of metalloproteinase-1 and risk of cognitive impairment after acute ischaemic stroke.

The expression of tissue inhibitor metalloproteinase-1 (TIMP-1) significantly increased after acute cerebral ischaemia and involved in neurodegeneration. The purpose was to prospectively investigate the relationship between serum TIMP-1 with post-stroke cognitive impairment. Our participants were from an ancillary study of China Antihypertensive Trial in Acute Ischemic Stroke. 598 ischaemic stroke patients from seven participating hospitals were included. Cognitive impairment was evaluated using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months. 316 (52.84%) or 384 (64.21%) participants had cognitive impairment according to MMSE or MoCA, respectively. Compared with the first quartile of TIMP-1, the multivariate-adjusted odds ratios (95% confidence intervals) for the highest quartile were 1.80 (1.09-2.97) for cognitive impairment defined by MMSE and 2.55 (1.49-4.35) by MoCA. Multiple-adjusted spline regression models showed linear associations between TIMP-1 concentrations and cognitive impairment (P value for linearity < 0.01). The addition of TIMP-1 to models including conventional factors improved reclassification for cognitive impairment, as shown by net reclassification index or integrated discrimination improvement (P < 0.05). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had highest risk of cognitive impairment. Higher serum TIMP-1 levels were associated with increased risk of cognitive impairment after acute ischaemic stroke, independently of established risk factors.

Longitudinal Average Glucose Levels and Variance and Risk of Stroke: A Chinese Cohort Study.

BACKGROUND: Diabetes is a known independent risk factor for stroke. However, whether higher glucose levels (126-139.9 mg/dl) can increase the risk of stroke in people without diabetes is still unknown. Moreover, as a fluctuating parameter, long-term glucose levels may also be related to the risk of stroke outcome. It is important to explore the correlation between long-term average blood glucose, as well as its variability, and stroke. METHODS: We used 40,975 clinical measurements of glucose levels and 367 measurements of glycated hemoglobin A1c levels from 12,321 participants without stroke to examine the relationship between glucose levels and the risk of stroke. Participants were from the Weitang Geriatric Diseases study, including 5,707 men and 6,614 women whose mean age at baseline was 60.8 years; 1,011 participants had diabetes, and 11,310 did not. We estimated the long-term average blood glucose level based on the multilevel Bayesian model and fit in Cox regression models, stratified according to diabetes status. RESULTS: Over a median follow-up period of 5 years, stroke developed in 279 of the 12,321 participants (244 without diabetes and 35 with). For people with an average glucose level of 126-139.9 mg per deciliter, compared with 90-99.9 mg per deciliter, the adjusted hazard ratio (HR) for total stroke was 1.78 (95% confidence interval (CI), 1.16-2.75), and the HR for levels higher than 140 mg per deciliter was 1.89 (95% CI, 1.09-3.29). Among those without diabetes whose glucose level was higher than 140 mg per deciliter, compared with 90-99.9 mg per deciliter, the adjusted HRs for total stroke and fatal stroke were 3.66 (95% CI, 1.47-9.08) and 5 (95% CI, 1.77-14.15), respectively. For a glucose standard deviation level higher than 13.83 mg per deciliter, compared with that lower than 5.91 mg per deciliter, the adjusted HR for total stroke was 2.31 (95% CI, 1.19-4.48). CONCLUSIONS: Our results suggest that higher average glucose levels (126-139.9 mg/dl) and variance may be risk factors for stroke, even among people without diabetes diagnosis.

[Average blood glucose construction: a multi-level Bayes model approach and application].

OBJECTIVE: To explore the average blood glucose construction method based on the multi-level Bayes model and evaluate the example application. METHODS: We generate simulated data with multi-level Bayes model. Three methods were utilized to construct the average blood glucose at the same time, then we compared the result with each other. A cohort study method was used to select 12321 participants aged over 45 y who without stroke in a community in Suzhou and was followed up from 2011 to 2018, of which 53. 7% were male. Mean blood glucose calculated by the most accurate complete Bayesian method was divided into six groups. The Cox regression model was used to analyze the effect of mean blood glucose on the incidence of fatal stroke. RESULTS: 1000 times of simulation result showed that the average mean blood glucose estimation calculated by the complete Bayesian method was 0. 278, the average of blood glucose estimation was 0. 527 mmol/L, and the average correlation coefficient with the actual blood glucose was r=0. 898. During the follow-up period, 153 fatal strokes occurred. Association was found between the mean blood glucose and the risk of fatal stroke(P<0. 05). The average risk of blood glucose over 140 mg/dL was 2. 304 times that of 90-99 mg/dL(HR=2. 304, 95%CI 1. 151-4. 613) after the adjustment of effects. CONCLUSION: The complete Bayesian multi-level latent variable model can accurately estimate the average blood glucose.

Serum Matrix Metalloproteinase-9 Is Associated With Depression After Acute Ischemic Stroke.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, might cause cerebral damage after stroke and be involved in the development of depressive symptoms. This study aimed to evaluate the association of serum MMP-9 levels and post-stroke depression (PSD).Methods and Results:Serum MMP-9 levels were determined in 558 acute ischemic stroke patients from 7 hospitals comprising the China Antihypertensive Trial in Acute Ischemic Stroke. We assessed depression status using the 24-item Hamilton Depression Rating Scale and defined PSD as a cutoff score of 8. Logistic regression was performed to estimate the risk of PSD associated with serum MMP-9. Discrimination and reclassification for PSD by MMP-9 were analyzed. A total of 222 (39.8%) stroke patients were categorized as PSD within 3 months. Serum MMP-9 concentrations were higher among PSD patients than those without PSD (658.8 vs. 485.7 ng/mL; P<0.001). The multiple-adjusted odds ratio (95% confidence interval) for the highest MMP-9 quartile compared with the lowest quartile was 4.36 (2.49-7.65) for PSD, and 1 standard deviation higher log-MMP-9 was associated with 68% (37-106%) increased odds of PSD. Adding MMP-9 to the conventional risk factors model substantially improved discrimination and reclassification for PSD (all P<0.05). CONCLUSIONS: Elevated serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of PSD, suggesting an important prognostic role of MMP-9 for PSD.