蒋立新
中国医学科学院阜外医院 心血管内科
Background:Although increased age is associated with higher systolic blood pressure (SBP) in general, there may be variation across individuals in how SBP changes over time. The goal of this paper is to identify heterogeneity in SBP trajectories among young adults with similar initial values and identify personal characteristics associated with different trajectory patterns. This may have important implications for prevention and prognosis.Methods:A cohort of 12,468 individuals aged 18-35 years in the Qingdao Port Cardiovascular Health Study in China was followed yearly during 2000-2011. Individuals were categorized into three strata according to their baseline SBP: ≤110 mmHg, 111-130 mmHg, and >130 mmHg. Within each stratum, group-based trajectory analyses were conducted to identify distinct SBP trajectory patterns, and their association with sociodemographic and baseline health characteristics was assessed by ordinal logistic regression.Results:Five distinct groups of individuals exhibiting divergent patterns of increasing, stable or decreasing SBP trends were identified within each stratum. This is a first report to identify a subgroup with decreasing trend in SBP. Individuals with more advanced age, having less than high school education, family history of cardiovascular diseases, greater body mass index, greater waist circumference, and hyperlipidemia at baseline were more likely to experience trajectories of higher SBP within each stratum.Conclusions:The diverging trajectories among young adults with similar initial SBP highlight the need for prevention and feasibility of effective blood pressure control, while the identified risk factors may inform targeted interventions.
Global heart 2020
BACKGROUND AND AIMS:Familial hypercholesterolemia (FH) is a an autosomal dominant disorder characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). It is estimated that >85% of all FH-causing mutations involve genetic variants in the LDL receptor (LDLR). To date, 795 single amino acid LDLR missense mutations have been reported in the Leiden Open Variation Database (LOVD). However, the functional impact of these variants on the LDLR pathway has received little attention and remains poorly understood. We aim to establish a systematic functional prediction model for LDLR single missense mutations.METHODS:Using a combined structural modeling and bioinformatics algorithm, we developed an in silico prediction model called "Structure-based Functional Impact Prediction for Mutation Identification" (SFIP-MutID) for FH with LDLR single missense mutations. We compared the pathogenicity and functional impact predictions of our model to those of other conventional tools with experimentally validated variants, as well as in vitro functional test results for patients with LDLR variants.RESULTS:Our SFIP-MutID model systematically predicted 13,167 potential LDLR single amino acid missense substitutions with biological effects. The functional impact of 52 out of 54 specific mutations with reported in vitro experimental data was predicted correctly. Further functional tests on LDLR variants from patients were also consistent with the prediction of our model.CONCLUSIONS:Our LDLR structure-based computational model predicted the pathogenicity of LDLR missense mutations by linking genotypes with LDLR functional phenotypes. Our model complements other prediction tools for variant interpretation and facilitates the precision diagnosis and treatment of FH and atherosclerotic cardiovascular diseases.
Atherosclerosis 2019
OBJECTIVE:To examine the association of kidney stones with new-onset hypertension, diabetes and obesity.PARTICIPANTS AND METHODS:This prospective cohort study included participants in the Qingdao Port Cardiovascular Health Study who were aged ≥18 years and had abdominal ultrasonography results in 2013 that were negative for kidney stones. Multivariable Cox regression models with time-dependent covariates were used to estimate the effects of new-onset hypertension, diabetes and obesity on the incidence of kidney stones.RESULTS:There were 9667 participants without kidney stones in 2013 (mean age 46.2 years; 75.6% men). During a mean (range) follow-up of 33.5 (6-42) months, 676 (7.0%) incident cases of kidney stones were identified. Kidney stones were more frequent among those who had new-onset of a metabolic factor vs those who did not (hypertension: 7.7 vs 6.0%; diabetes: 8.4 vs 6.6%; obesity: 7.4 vs 6.8%). Adjusted Cox models identified that increased risk of kidney stones was associated with new-onset hypertension (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.25-2.27), new-onset diabetes (HR 1.78, 95% CI 1.07-2.96), and new-onset obesity (HR 1.78, 95% CI 1.15-2.74).CONCLUSIONS:New-onset of hypertension, diabetes and obesity were all strongly associated with an increased risk of kidney stones in this prospective cohort study. Results suggest that a substantial proportion of kidney stones are potentially preventable by appropriate control of these metabolic risk factors.
BJU international 2019
BACKGROUND:We examined sex differences in long-term health outcomes following acute myocardial infarction in China, including mortality, major adverse cardiac events and health status (symptoms, functioning, quality of life).METHODS:A total of 3415 acute myocardial infarction patients (23.2% women) aged ⩾18 years were enrolled across 10 geographic regions in China (2012-2014) in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) study. Clinical data was abstracted from medical records. Generic (Euro-Quality of Life Scale) and disease-specific (Seattle Angina Questionnaire) health status was obtained through interviews at baseline and one year.RESULTS:At one year, women with acute myocardial infarction had a higher risk of death from all causes ( p<0.001), but had similar rates of major adverse cardiac events ( p=0.2). Women had lower mean generic (Euro-Quality of Life Scale utility index score: 0.90±0.13 vs 0.94±0.11) and disease specific health scores indicating poorer functioning (Seattle Angina Questionnaire summary score: 75.3±11.4 vs 78.4±9.7) and higher rates of daily/weekly angina (Seattle Angina Questionnaire angina frequency score ⩽60 vs >60: 9.1% vs 4.7%; all p<0.001). In multivariable analysis, there was a significant association between female sex and mortality (β=0.45, standard error=0.21, p=0.03) but not for major adverse cardiac events (β=-0.02, standard error=0.14, p=0.89). The association between female sex and worse generic health status persisted (β=-0.02, standard error=0.01, p=0.003), but was no longer significant between sexes for disease-specific health status (β=-0.82, standard error=0.58, p=0.154) or daily/weekly angina (odds ratio=1.39; 95% confidence interval 0.88-2.21).CONCLUSION:Women in China have higher crude rates of all-cause/cardiovascular death versus men, as well as worse generic/disease specific health status at one-year post-acute myocardial infarction. The association between female sex and worse generic health status persisted following adjustment.
European heart journal. Acute cardiovascular care 2019
OBJECTIVE:To assess the association between educational attainment and acute myocardial infarction (AMI) outcomes in China to inform future healthcare interventions.METHODS:We used data from the China Patient-centred Evaluative Assessment of Cardiac Events-Prospective AMI study of 3369 consecutive patients hospitalised with AMI from 53 hospitals. Educational attainment was categorised as: high (senior high school, college or postgraduate degree), intermediate (junior high school) or low (primary school or illiterate). We used survival models to assess the relationship between education and 1-year major adverse cardiovascular events (MACE), all-cause mortality, both unadjusted and after adjustment for demographic characteristics and cardiovascular risk factors.RESULTS:The median participant age was 61 (52, 69) years, 23.2% were women, and 33.3% had high, 32.4% intermediate and 34.3% low educational attainment. In unadjusted analysis, compared with high educational attainment, low educational attainment was associated with a higher 1-year risk of MACE (HR 2.41, 95% CI 1.72 to 3.37) and death (HR for low vs high education 3.09, 95% CI 1.69 to 5.65). In risk-adjusted analyses, the association between education and death was attenuated and no longer statistically significant (adjusted HR 1.41, 95% CI 0.74 to 2.69, p=0.30). However, the risk of 1-year MACE (adjusted HR 1.68, 95% CI 1.18 to 2.41, p=0.004) remained significantly greaterin low educational attainment group.CONCLUSIONS:In a national Chinese cohort of patients hospitalised with AMI, low educational attainment was associated with a higher risk of adverse events in the year following discharge. This association highlights the need to consider interventions to improve AMI outcomes in adults with low levels of education.CLINICAL TRIAL REGISTRATION:NCT01624909; Results.
Heart (British Cardiac Society) 2019
INTRODUCTION:China faces the prospect of a large growth in the prevalence of heart failure (HF). However, there is limited knowledge about outcomes in patients after HF hospitalisations, including patient-reported outcomes (PROs). This paper is to present the study goal, methodology and data collection of the China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study).METHODS AND ANALYSIS:The China PEACE 5p-HF Study, a prospective cohort study, will enrol 5000 patients with HF during 2016-2018 from 52 diverse hospitals throughout China and the follow-up period will be 12 months. Information on patients' medical history, in-hospital treatment and in-hospital outcomes are being abstracted from medical records. Details of patients' demographics, socioeconomic status, cardiovascular risk factors, access to healthcare services are being collected through comprehensive baseline interviews. Generic and disease-specific health status, depression, stress, anxiety and cognitive function are being administered using validated PRO instruments. Follow-up interviews will capture PROs and hospitalisation events at 1, 6 and 12 months follow-up. Standardised transthoracic echocardiograms and 6 min walk tests are being done in patients who enrolled in hospitals with these facilities at baseline and at 1 and 12 months after discharge. Collection of blood and urine samples are also being conducted at baseline, 1 and 12 months follow-up and stored for future analyses.ETHICS AND DISSEMINATION:The National Center for Cardiovascular Diseases/Fuwai Hospital ethics committee approved this study, and all collaborating hospitals received approval from their local ethics committee. Written informed consent will be obtained from all patients. Findings will be disseminated in future peer-reviewed papers and will help to support improvements in the quality of care for HF nationwide.TRIAL REGISTRATION NUMBER:NCT02878811.
BMJ open 2019
BACKGROUND:The efficacy of ticagrelor in the long-term post-ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.OBJECTIVES:The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.METHODS:This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.RESULTS:The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.CONCLUSION:Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088).
Journal of the American College of Cardiology 2019
Aims:Few contemporary studies have reported the time between acute myocardial infarction (AMI) symptoms onset and hospital arrival, associated factors, and patient perceptions of AMI symptoms and care seeking. We sought to study these issues using data from China, where AMI hospitalizations are increasing.Methods and results:We used data from the China PEACE prospective AMI study of 53 hospitals across 21 provinces in China. Patients were interviewed during index hospitalization for information of symptom onset, and perceived barriers to accessing care. Regression analyses were conducted to explore factors associated with the time between symptom onset and hospital arrival. The final sample included 3434 patients (mean age 61 years). The median time from symptom onset to hospital arrival was 4 h (interquartile range 2-7.5 h). While 94% of patients reported chest pain or chest discomfort, only 43% perceived symptoms as heart-related. In multivariable analyses, time to hospital arrival was longer by 14% and 39% for patients failing to recognize symptoms as cardiac and those with rural medical insurance, respectively (both P < 0.001). Compared with patients with household income over 100 000 RMB, those with income of 10 000-50 000 RMB, and <10 000 RMB had 16% and 23% longer times, respectively (both P = 0.03).Conclusion:We reported an average time to hospital arrival of 4 h for AMI in China, with longer time associated with rural medical insurance, failing to recognize symptoms as cardiac, and low household income. Strategies to improve the timeliness of presentation may be essential to improving outcomes for AMI in China.Clinical trial registration:https://clinicaltrials.gov/ct2/show/NCT01624909.
European heart journal. Quality of care & clinical outcomes 2019
Importance:Body mass index (BMI) is positively associated with blood pressure (BP); this association has critical implications for countries like China, where hypertension is highly prevalent and obesity is increasing. A greater understanding of the association between BMI and BP is required to determine its effect and develop strategies to mitigate it.Objective:To assess the heterogeneity in the association between BMI and BP across a wide variety of subgroups of the Chinese population.Design, Setting, and Participants:In this cross-sectional study, data were collected at 1 time point from 1.7 million adults (aged 35-80 years) from 141 primary health care sites (53 urban districts and 88 rural counties) from all 31 provinces in mainland China who were enrolled in the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, conducted between September 15, 2014, and June 20, 2017. A comprehensive subgroup analysis was performed by defining more than 22 000 subgroups of individuals based on covariates, and within each subgroup, linearly regressing BMI to BP.Main Outcomes and Measures:Systolic BP was measured twice with the participant in a seated position, using an electronic BP monitor.Results:The study included 1 727 411 participants (1 027 711 women and 699 700 men; mean [SD] age, 55.7 [9.8] years). Among the study sample, the mean (SD) BMI was 24.7 (3.5), the mean (SD) systolic BP was 136.5 (20.4) mm Hg, and the mean (SD) diastolic BP was 81.1 (11.2) mm Hg. The increase of BP per unit BMI ranged from 0.8 to 1.7 mm Hg/(kg/m2) for 95% of the subgroups not taking antihypertensive medication. The association between BMI and BP was substantially weaker in subgroups of patients taking antihypertensive medication compared with those who were untreated. In untreated subgroups, 95% of the coefficients varied by less than 1 mm Hg/(kg/m2).Conclusions and Relevance:The association between BMI and BP is positive across tens of thousands of individuals in population subgroups, and, if causal, given its magnitude, would have significant implications for public health.
JAMA network open 2018
BACKGROUND:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular (CV) disease. Whether plasma PCSK9 measured during the acute phase predicts recurrent CV events in patients with acute myocardial infarction (AMI) remains unresolved.METHODS AND RESULTS:Plasma PCSK9 levels were measured in 1,646 patients with AMI from the China PEACE-Prospective AMI Study at the acute phase. Additionally, 248 patients were resampled and measured at 1 month post-AMI. Associations of acute-phase PCSK9 tertiles with clinical characteristics and recurrent CV events within 1 year were assessed. Female gender (OR 1.94, 95% CI 1.24-3.03), premature coronary heart disease (CHD; OR 2.12, 95% CI 1.37-3.26), higher high-sensitivity C-reactive protein (OR 1.67, 95% CI 1.44-1.95), and higher triglycerides (OR 1.46, 95% CI 1.03-2.09) were associated with higher baseline PCSK9. Plasma PCSK9 levels in the highest tertile (versus lowest) did not have an increased risk of 1-year recurrent CV events in the AMI cohort (HR 0.78, 95% CI 0.52-1.16) or any subgroup. There was also no association between percentage changes in PCSK9 over the first month and 1-year recurrent events, although there was a trend of differences between patients in the upper versus lower tertiles.CONCLUSION:Plasma PCSK9 levels measured during the acute phase were associated with high-sensitivity C-reactive protein, triglycerides, premature CHD, and gender in patients with AMI but did not predict recurrent CV events within 1 year. Dynamic changes in PCSK9 suggested a trend yet no significance value in predicting recurrent CV events.
Cardiology 2018
