黄辰
中国医学科学院阜外医院 群体遗传教研室
BACKGROUND:To explore how central hemodynamics respond to dietary sodium and potassium interventions, and whether the responses are associated with metabolic traits.METHODS:We conducted a dietary intervention study including a 7-day low-sodium (51.3 mmol sodium/day) intervention, a 7-day high-sodium (307.8 mmol sodium/day) intervention, and a 7-day high-sodium with potassium supplementation (60.0 mmol potassium/day) intervention among 99 northern Chinese subjects aged 18-60 years. Five metabolic traits included abdominal obesity, high triglycerides, low HDL cholesterol, raised blood pressure (BP), and high glucose. Central hemodynamics were measured at baseline and during each intervention.RESULTS:Central systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and augmentation index (AIx@75) significantly decreased during low-sodium intervention, increased during high-sodium intervention, and then decreased during potassium supplementation. We observed potential linear trends toward significance of central SBP and PP responses to low-sodium intervention, and significant linear trends of responses to high-sodium intervention as the number of metabolic traits grows. For example, among participants with 0 or 1, 2 or 3, and 4 or 5 metabolic traits, central SBP responses to high-sodium intervention were 8.8 [95% confidence interval (5.8, 11.8)], 9.3 (7.1, 11.6), and 14.0 (11.6, 16.3) mmHg, respectively (P for trend = 0.009). Significant linear trends of central SBP and DBP responses to potassium supplementation were also observed.CONCLUSIONS:Central BP and AIx@75 were lowered by sodium reduction and potassium supplementation, and elevated by sodium-loading. The responses of central BP were pronounced among individuals with metabolic traits clustering.CLINICAL TRIALS REGISTRATION:Trial Number NCT00721721 (The current study is registered on ClinicalTrials.gov; https://clinicaltrials.gov).
American journal of hypertension 2018
In many gastric cancer patients, the disease is diagnosed in an advanced stage and therefore the mortality levels are high. Because there is a need to identify novel early diagnostic and prognostic biomarkers, we tested whether SIRT1 and STAT3 are good candidates. Towards this, we used patient tissues representing different stages of gastric cancer including gastric pre-cancerous lesions, early gastric cancer, and advanced gastric cancer, and probed SIRT1, STAT3 and phosphorylated STAT3 (pSTAT3) levels using immunohistochemistry. Our results revealed upregulated expression of SIRT1 in all stages of gastric cancer compared with noncancerous gastric mucosa, suggesting that high SIRT1 levels are likely involved in establishing gastric neoplasticity. However, STAT3 and pSTAT3 levels remained low until the gastric mucosa reached the tumor stage. Moreover, co-ordinated high expression of SIRT1 and STAT3 predicted poor overall survival for advanced gastric cancer patients. In addition, through analysis of gastric cancer patients from the TCGA dataset, we identified SIRT2 as an independent prognostic factor in gastric cancer patients. We postulate that SIRT1 and STAT3 are potential early diagnostic and prognostic markers of gastric cancer. Our study also shows that SIRT1 acts a gatekeeper during gastric tumorigenesis.
Oncotarget 2017
BACKGROUND:Outdoor air pollution ranks fourth among preventable causes of China's burden of disease. We hypothesized that the magnitude of health gains from air quality improvement in urban China could compare with achieving recommended blood pressure or smoking control goals.METHODS:The Cardiovascular Disease Policy Model-China projected coronary heart disease, stroke, and all-cause deaths in urban Chinese adults 35 to 84 years of age from 2017 to 2030 if recent air quality (particulate matter with aerodynamic diameter ≤2.5 µm, PM2.5) and traditional cardiovascular risk factor trends continue. We projected life-years gained if urban China were to reach 1 of 3 air quality goals: Beijing Olympic Games level (mean PM2.5, 55 μg/m3), China Class II standard (35 μg/m3), or World Health Organization standard (10 μg/m3). We compared projected air pollution reduction control benefits with potential benefits of reaching World Health Organization hypertension and tobacco control goals.RESULTS:Mean PM2.5 reduction to Beijing Olympic levels by 2030 would gain ≈241,000 (95% uncertainty interval, 189 000-293 000) life-years annually. Achieving either the China Class II or World Health Organization PM2.5 standard would yield greater health benefits (992 000 [95% uncertainty interval, 790 000-1 180 000] or 1 827 000 [95% uncertainty interval, 1 481 00-2 129 000] annual life-years gained, respectively) than World Health Organization-recommended goals of 25% improvement in systolic hypertension control and 30% reduction in smoking combined (928 000 [95% uncertainty interval, 830 000-1 033 000] life-years).CONCLUSIONS:Air quality improvement in different scenarios could lead to graded health benefits ranging from 241 000 life-years gained to much greater benefits equal to or greater than the combined benefits of 25% improvement in systolic hypertension control and 30% smoking reduction.
Circulation 2017
BACKGROUND:The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population.METHODS:We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.RESULTS:Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4).CONCLUSIONS:These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted.
American journal of hypertension 2017
BACKGROUND AND AIMS:Studies of the association between obesity and total mortality and recurrent stroke events have shown contradictory results. Therefore, we aimed to conduct a meta-analysis to examine the association of body mass index (BMI) with total mortality and recurrent stroke events among patients after stroke onset.METHODS:We performed an electronic search of PubMed, EMBASE and the Cochrane Library Database, as well as a bibliography review to identify relevant cohort studies published prior to 15th December 2015. Estimates of relative risks (RRs) and corresponding 95% confidence intervals (CIs) comparing underweight, overweight and obese groups with normal weight were pooled using random effects models.RESULTS:In total, 15 studies with 122,472 stroke patients were eligible for inclusion in the meta-analysis. Compared with the normal weight group, obese stroke patients had a significant decreased risk for total mortality (RR = 0.83, 95% CI, 0.73-0.93, p = 0.002), while underweight patients had a significant increased risk for total mortality (RR = 1.54, 95% CI, 1.31-1.82, p = 3.66 × 10-7). A similar, but not significant, association of BMI categories with recurrent stroke events was also observed. Furthermore, the dose-response meta-analysis identified a nonlinear trend for total mortality and a linear trend for recurrent stroke events, associated with BMI.CONCLUSIONS:Our results suggested that obesity may have a protective effect on total mortality and recurrent stroke events among patients with established stroke.
Atherosclerosis 2016
OBJECTIVE:To evaluate the influence of overweight/obesity on the incidence of hypertension among adults in China.METHODS:The subjects of this prospective study were 13 739 Chinese adults aged 35-74 years recruited at the baseline surveys of China Multicenter Collaborative Study of Cardiovascular Disease Epidemiology and International Collaborative Study of Cardiovascular Disease in Asian. Baseline surveys were conducted in 1998 and during 2000-2001, respectively, and the follow-up was conducted during 2007-2008. According to the body mass index, the subjects were divided into four groups: underweight group(<18.5 kg/m(2)), normal weight group(18.5-23.9 kg/m(2)), overweight group(24.0-27.9 kg/m(2))and obesity group(≥28.0 kg/m(2)). Age-standardized cumulative incidence of hypertension was calculated for each group, respectively. The relative risks(RRs)and 95% confidence intervals(CIs)for the incidence of hypertension of underweight, overweight and obesity groups were estimated by using generalized linear regression model with normal weight group as reference.RESULTS:During 8.1 years of follow-up, 4 271 hypertension cases were detected(2 012 in men and 2 259 in women). Age-standardized cumulative incidence of hypertension for the underweight, normal weight, overweight and obesity groups were 20.3%, 30.9%, 43.6% and 50.8% in men, respectively; and 22.9%, 30.4%, 41.1% and 50.8% in women, respectively. Compared with the normal weight group, multivariate-adjusted RR(95% CI)for the incidence of hypertension in underweight, overweight and obesity groups were 0.78(0.64-0.95), 1.22(1.13-1.30)and 1.28(1.16-1.42)in men, respectively; and 0.89(0.77-1.03), 1.16(1.09-1.23)and 1.28(1.18-1.38)in women, respectively. The overweight and obese subjects had higher risk for the incidence of hypertension, with the population attributable risk proportion of 7.4% in men and 8.8% in women, respectively.CONCLUSION:Overweight or obese people are at an increased risk of developing hypertension, thus prevention and control of overweight/obesity are needed to reduce hypertension incidence among adults in China.
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2016
OBJECTIVE:To examine the awareness, treatment and control rates of diabetes and identify their associated risk factors among Beijing residents.METHODS:A cross-sectional survey was conducted in 2011, using a stratified multistage cluster random sampling method to select a representative sample of 20,242 residents in Beijing aged 18-79 years. Diabetes was defined as fasting blood glucose (FBG) ≥7.0 mmol/L and/or history of diabetes and/or using insulin or hypoglycemic agents. All estimates of awareness, treatment and control rates were weighted by the 2010 Beijing Population Census data and the sampling scheme. Multivariate Logistic regression was used to identify factors associated with awareness, treatment and control rates.RESULTS:A total of 2061 (10.3%) participants were diagnosed as diabetes. The overall awareness, treatment and control rate among patients were 60.9%, 51.3% and 22.4%, respectively, while overall control rate among treated patients was 33.8%. These rates differed across subgroups. Women were more likely to be aware of diabetes status, receive treatment and have better glucose controlled than men (69.5% vs. 54.7% for awareness, 61.0% vs. 44.3% for treatment, and 27.6% vs. 18.6% for control, respectively). In addition, only 22.2% of treated patients had both FBG and hemoglobin A1c (HbA1c) controlled well. Multivariate Logistic regression suggested that old age, women, higher education and family history of diabetes were associated with higher awareness, treatment and control rates (All P < 0.05). Treated individuals living in rural (OR = 0.67(95%CI: 0.47-0.96)) or with dyslipidemia (OR = 0.63 (95%CI: 0.44-0.91)) had a lower diabetic control rate.CONCLUSIONS:Awareness, treatment and control rates of diabetes in Beijing were still low. A comprehensive intervention strategy on diabetes management and control is warranted.
Chronic diseases and translational medicine 2016
The population health effect and cost-effectiveness of implementing intensive blood pressure goals in high-cardiovascular disease (CVD) risk adults have not been described. Using the CVD Policy Model, CVD events, treatment costs, quality-adjusted life years, and drug and monitoring costs were simulated over 2016 to 2026 for hypertensive patients aged 35 to 74 years. We projected the effectiveness and costs of hypertension treatment according to the 2003 Joint National Committee (JNC)-7 or 2014 JNC8 guidelines, and then for adults aged ≥50 years, we assessed the cost-effectiveness of adding an intensive goal of systolic blood pressure <120 mm Hg for patients with CVD, chronic kidney disease, or 10-year CVD risk ≥15%. Incremental cost-effectiveness ratios <$50 000 per quality-adjusted life years gained were considered cost-effective. JNC7 strategies treat more patients and are more costly to implement compared with JNC8 strategies. Adding intensive systolic blood pressure goals for high-risk patients prevents an estimated 43 000 and 35 000 annual CVD events incremental to JNC8 and JNC7, respectively. Intensive strategies save costs in men and are cost-effective in women compared with JNC8 alone. At a willingness-to-pay threshold of $50 000 per quality-adjusted life years gained, JNC8+intensive had the highest probability of cost-effectiveness in women (82%) and JNC7+intensive the highest probability of cost-effectiveness in men (100%). Assuming higher drug and monitoring costs, adding intensive goals for high-risk patients remained consistently cost-effective in men, but not always in women. Among patients aged 35 to 74 years, adding intensive blood pressure goals for high-risk groups to current national hypertension treatment guidelines prevents additional CVD deaths while saving costs provided that medication costs are controlled.
Hypertension (Dallas, Tex. : 1979) 2016
BACKGROUND:We compared the cost-effectiveness of hypertension treatment in non-Hispanic blacks and non-Hispanic whites according to 2014 US hypertension treatment guidelines.METHODS:The cardiovascular disease (CVD) policy model simulated CVD events, quality-adjusted life years (QALYs), and treatment costs in 35- to 74-year-old adults with untreated hypertension. CVD incidence, mortality, and risk factor levels were obtained from cohort studies, hospital registries, vital statistics, and national surveys. Stage 1 hypertension was defined as blood pressure 140-149/90-99mm Hg; stage 2 hypertension as ≥150/100mm Hg. Probabilistic input distribution sampling informed 95% uncertainty intervals (UIs). Incremental cost-effectiveness ratios (ICERs) < $50,000/QALY gained were considered cost-effective.RESULTS:Treating 0.7 million hypertensive non-Hispanic black adults would prevent about 8,000 CVD events annually; treating 3.4 million non-Hispanic whites would prevent about 35,000 events. Overall 2014 guideline implementation would be cost saving in both groups compared with no treatment. For stage 1 hypertension but without diabetes or chronic kidney disease, cost savings extended to non-Hispanic black males ages 35-44 but not same-aged non-Hispanic white males (ICER $57,000/QALY; 95% UI $15,000-$100,000) and cost-effectiveness extended to non-Hispanic black females ages 35-44 (ICER $46,000/QALY; $17,000-$76,000) but not same-aged non-Hispanic white females (ICER $181,000/QALY; $111,000-$235,000).CONCLUSIONS:Compared with non-Hispanic whites, cost-effectiveness of implementing hypertension guidelines would extend to a larger proportion of non-Hispanic black hypertensive patients.
American journal of hypertension 2016
BACKGROUND:Hypertension is China's leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world's largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.METHODS AND FINDINGS:The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35-84 y over 2015-2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140-159/90-99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100% of probabilistic simulation results. Treating all hypertension for primary and secondary prevention would prevent about 800,000 cardiovascular disease events annually (95% uncertainty interval, 0.6 to 1.0 million) and was borderline cost-effective incremental to treating only cardiovascular disease and stage two patients (2015 Int$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China.CONCLUSIONS:Expanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.
PLoS medicine 2015
