Changwei Li

Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis

Importance Clinical trials have documented that lowering blood pressure reduces cardiovascular disease and premature deaths. However, the optimal target for reduction of systolic blood pressure (SBP) is uncertain. Objective To assess the association of mean achieved SBP levels with the risk of cardiovascular disease and all-cause mortality in adults with hypertension treated with antihypertensive therapy. Data Sources MEDLINE and EMBASE were searched from inception to December 15, 2015, supplemented by manual searches of the bibliographies of retrieved articles. Study Selection Studies included were clinical trials with random allocation to an antihypertensive medication, control, or treatment target. Studies had to have reported a difference in mean achieved SBP of 5 mm Hg or more between comparison groups. Data Extraction and Synthesis Data were extracted from each study independently and in duplicate by at least 2 investigators according to a standardized protocol. Network meta-analysis was used to obtain pooled randomized results comparing the association of each 5–mm Hg SBP category with clinical outcomes after adjusting for baseline risk. Main Outcomes and Measures Cardiovascular disease and all-cause mortality. Results Forty-two trials, including 144 220 patients, met the eligibility criteria. In general, there were linear associations between mean achieved SBP and risk of cardiovascular disease and mortality, with the lowest risk at 120 to 124 mm Hg. Randomized groups with a mean achieved SBP of 120 to 124 mm Hg had a hazard ratio (HR) for major cardiovascular disease of 0.71 (95% CI, 0.60-0.83) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.58 (95% CI, 0.48-0.72) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.46 (95% CI, 0.34-0.63) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.36 (95% CI, 0.26-0.51) compared with those with a mean achieved SBP of 160 mm Hg or more. Likewise, randomized groups with a mean achieved SBP of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73 (95% CI, 0.58-0.93) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.59 (95% CI, 0.45-0.77) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.51 (95% CI, 0.36-0.71) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.47 (95% CI, 0.32-0.67) compared with those with a mean achieved SBP of 160 mm Hg or more. Conclusions and Relevance This study suggests that reducing SBP to levels below currently recommended targets significantly reduces the risk of cardiovascular disease and all-cause mortality. These findings support more intensive control of SBP among adults with hypertension.

Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci

We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26 600 East Asian participants (stage 1) followed by replication study of up to 28 783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10–8 in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10–3. No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10–15), rs2681492 at ATP2B1 (P=3.4×10–7), rs11191593 at NT5C2 (1.1×10–6), rs3824755 at CYP17A1 (P=1.2×10–6), and rs13149993 at FGF5 (P=2.4×10–4). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10–5) and rs11191593 at NT5C2 (P=1.1×10–3), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10–3) and rs2681492 at ATP2B1 (P=9.0×10–3). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.

Mobile Phone Intervention and Weight Loss Among Overweight and Obese Adults: A Meta-Analysis of Randomized Controlled Trials

We conducted a meta-analysis of randomized controlled trials to examine the association of mobile phone intervention with net change in weight-related measures among overweight and obese adults. We searched electronic databases and conducted a bibliography review to identify articles published between the inception date of each database and March 27, 2014. Fourteen trials (including 1,337 participants in total) that met the eligibility criteria were included. Two investigators independently abstracted information on study characteristics and study outcomes. Net change estimates comparing the intervention group with the control group were pooled across trials using random-effects models. Compared with the control group, mobile phone intervention was associated with significant changes in body weight and body mass index (weight (kg)/height (m)(2)) of -1.44 kg (95% confidence interval (CI): -2.12, -0.76) and -0.24 units (95% CI: -0.40, -0.08), respectively. Subgroup analyses revealed that the associations were consistent across study-duration and intervention-type subgroups. For example, net body weight changes were -0.92 kg (95% CI: -1.58, -0.25) and -1.85 kg (95% CI: -2.99, -0.71) in trials of shorter (<6 months) and longer (≥6 months) duration, respectively. These findings provide evidence that mobile phone intervention may be a useful tool for promoting weight loss among overweight and obese adults.

Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Importance Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke. Objective To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke. Data Sources MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015. Study Selection Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected. Data Extraction and Synthesis Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes. Main Outcomes and Measures The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage. Results Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration. Conclusions and Relevance This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment.

Progress and future aspects in genetics of human hypertension.

Hypertension has become a major global health burden due to its high prevalence and associated increase in risk of cardiovascular disease and premature death. It is well established that hypertension is determined by both genetic and environmental factors and their complex interactions. Recent large-scale meta-analyses of genome-wide association studies (GWAS) have successfully identified a total of 38 loci which achieved genome-wide significance (P < 5 × 10-8) for their association with blood pressure (BP). Although the heritability of BP explained by these loci is very limited, GWAS meta-analyses have elicited renewed optimism in hypertension genomics research, highlighting novel pathways influencing BP and elucidating genetic mechanisms underlying BP regulation. This review summarizes evolving progress in the rapidly moving field of hypertension genetics and highlights several promising approaches for dissecting the remaining heritability of BP. It also discusses the future translation of genetic findings to hypertension treatment and prevention.

Prevalence and risk factors of arthritis in a middle-aged and older Chinese population: the China Health and Retirement Longitudinal Study

OBJECTIVES The aims of this study were to estimate the prevalence of arthritis and to identify risk factors of arthritis in a middle-aged and older Chinese adult population. METHODS The China Health and Retirement Longitudinal Study (CHARLS) national survey data were used to estimate overall arthritis prevalence and prevalence by age and gender groups taking into account the complex survey design and response rate. The PROC SURVEYLOGISTIC procedure (SAS 9.3; SAS Institute, Cary, NC, USA) was applied to identify factors associated with arthritis using the CHARLS national survey data. Significant factors were further evaluated in the longitudinal CHARLS pilot study. RESULTS The overall prevalence of arthritis among middle-aged and older Chinese adults was 31.4% (95% CI 30.3, 32.4). Prevalence increased with age. Females had a higher prevalence of arthritis than males in each age group. In the cross-sectional analysis, age, gender, education, BMI, sleep duration, vigorous physical activity and self-reported doctor-diagnosed chronic lung disease, hypertension, chronic liver disease, cardiovascular disease, stroke, chronic kidney disease and chronic digestive disease were associated with arthritis. Age, gender, vigorous physical activity and cardiovascular disease were confirmed to be risk factors of arthritis in the longitudinal analysis. Participants with cardiovascular disease were 1.67 times (95% CI 1.02, 2.74) more likely to have self-reported arthritis in a 4-year period of follow-up in the CHARLS pilot study. CONCLUSION Middle-aged and older Chinese adults had a high prevalence of arthritis. Cardiovascular disease is a novel risk factor for arthritis in this population.

Validity of self-reported diabetes among middle-aged and older Chinese adults: the China Health and Retirement Longitudinal Study

Background Self-reported diabetes has been found to be valid to evaluate peoples diabetes status in the population of several countries. However, no such study has been conducted to assess the validity of self-reported diabetes in the Chinese population, the largest population with the highest rate of diabetes. The aim of our study is to evaluate the validity of self-reported diabetes among the middle-aged and older Chinese population. Methods Data from 11 601 participants, aged ≥45, of the China Health and Retirement Longitudinal Study (CHARLS) during 2011–2012, were analysed. Prevalent self-reported diabetes was compared with reference definition defined by fasting glucose, glycated haemoglobin and medication use. Sensitivity, specificity, positive predicted value, negative predicted value and κ value were calculated overall, by 5-year age groups, by education levels and by living areas. Results The sensitivity of prevalent self-reported diabetes was 41.5%, and the specificity was 98.6%. The sensitivity of self-reported diabetes increased with education levels, and was much higher among urban residents than rural residents (58.2% vs 35.0%). The specificity was above 98% among all age groups, in different education levels, and in rural and urban areas. Self-reported diabetes had substantial agreement with reference definition among participants with above vocational school education or those living in urban areas (κ=0.658 and 0.646, respectively). Conclusions Although the sensitivity of self-reported diabetes was poor among middle-aged and older Chinese adults, the specificity and positive predictive values were fairly good. Furthermore, self-reported diabetes performed well among those with more than vocational school educations or those living in urban areas.

Smoking Experimentation among Elementary School Students in China: Influences from Peers, Families, and the School Environment

The aim of this study was to investigate experimentation with smoking among primary school students in China. Data were acquired from a recent survey of 4,073 students in grades 4 to 6 (ages 9–12) in 11 primary schools of Ningbo City. The questions were adapted from the Global Youth Tobacco Survey (GYTS). Results suggest that although the Chinese Ministry of Education (MOE) encourages smoke-free schools, experimentation with cigarettes remains a serious problem among primary school students in China. Peers, family members, and the school environment play important roles in influencing smoking experimentation among students. Having a friend who smoked, seeing a family member smoke, and observing a teacher smoking on campus predicted a higher risk of experimentation with smoking; the exposure to anti-tobacco materials at school predicted a lower risk of experimentation with smoking. The evidence suggests that public health practitioners and policymakers should seek to ensure the implementation of smoke-free policies and that intervention should target young people, families, and communities to curb the commencement of smoking among children and adolescents in China.

Factors Influencing Self-Management in Chinese Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Diabetes is a major public health problem in China. Diabetes self-management is critical for patients to achieved better health outcomes, however, previous studies have shown suboptimal diabetes self-management performance. We conducted a systematic review and meta-analysis to identify factors associated with diabetes self-management in Chinese adults. The results showed that confrontation, resignation, overall health beliefs, perceived susceptibility, perceived barriers, and self-efficacy were factors associated with overall diabetes self-management performance and six aspects of diabetes self-management behaviors. There is some limited evidence to suggest that provider-patient communication, married individuals, higher educational level, and higher household income level may also be linked to better diabetes self-management practice. Having healthcare insurance and utilizing chronic illness resources generally appeared to have a favorable effect on diabetes self-management performance. In addition, there were a number of factors for which the evidence is too limited to be able to ascertain its strength of association with diabetes self-management practice. The findings of this review suggest that diabetes self-management behaviors are affected by a wide range of personal and environmental factors, which allow health care providers to develop theory-based strategies to improve diabetes-self-management behaviors in this population.

Genome-Wide Gene–Sodium Interaction Analyses on Blood Pressure The Genetic Epidemiology Network of Salt-Sensitivity Study

We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker–based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings ( P <1.00×10–4) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP ( P =3.13×10–9). The 2 df tests additionally identified associations for CLGN rs2567241 ( P =3.90×10–12) and LOC105369882 rs11104632 ( P =4.51×10–8) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP ( P =3.11×10–22) and mean arterial pressure ( P =2.86×10–15). Genome-wide gene-based analysis identified MKNK1 ( P =6.70×10–7), C2orf80 ( P <1.00×10–12), EPHA6 ( P =2.88×10–7), SCOC-AS1 ( P =4.35×10–14), SCOC ( P =6.46×10–11), CLGN ( P =3.68×10–13), MGAT4D ( P =4.73×10–11), ARHGAP42 ( P ≤1.00×10–12), CASP4 ( P =1.31×10–8), and LINC01478 ( P =6.75×10−10) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium. # Novelty and Significance {#article-title-41}We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker–based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10–4) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10–9). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10–12) and LOC105369882 rs11104632 (P=4.51×10–8) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10–22) and mean arterial pressure (P=2.86×10–15). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10–7), C2orf80 (P<1.00×10–12), EPHA6 (P=2.88×10–7), SCOC-AS1 (P=4.35×10–14), SCOC (P=6.46×10–11), CLGN (P=3.68×10–13), MGAT4D (P=4.73×10–11), ARHGAP42 (P⩽1.00×10–12), CASP4 (P=1.31×10–8), and LINC01478 (P=6.75×10−10) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium.