The Impact of Particulate Matters Air Pollution on Accelerated Atherosclerosis: A Montelukast Interventional Study for Atherosclerosis Prevention in Modernizing China
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Brachial flow-mediated dilation (FMD)
研究概览
简要总结
Background: Longterm exposure to air pollution has been associated with cardiovascular events and mortality on top of traditional risk factors. Pulmonary inflammation and oxidative stress have been implicated. Brachial (arm) vascular reactivity (flow-mediated dilation FMD) and carotid (neck) artery intima-media thickness (CIMT) are highly reproducible atherosclerosis surrogates, predictive of cardiovascular and stroke outcome. Montelukast is proven safe and effective in alleviating pulmonary inflammation and oxidative stress when used in prevention of asthma episode.
Study objectives:
- To test the hypothesis of pulmonary inflammation and oxidative stress-related vascular dysfunction in PM air pollution.
- To evaluate the impact of Montelukast treatment as compared with placebo on predictive atherosclerosis surrogates (FMD and IMT).
Design: Parallel placebo control, randomized comparative study. Subjects will be randomized to take Montelukast (10mg/daily) or image-matched placebo for 26 weeks. Measures will include PM2.5/PM10, indices of subclinical atherosclerosis (brachial FMD and CIMT), blood inflammatory biomarkers (platelet counts, hsCRP and fibrinogen) and potential confounders (lipids and glucose).
Setting: 120 working adults aged 30-60 years in Hong Kong and 80 working adults in Chongqing (CREC Ref No: 2018.157, 2020.398)
Main outcome measures:
- Subclinical atherosclerosis: (a) Endothelial function (brachial FMD) and (b) carotid intima media thickness (CIMT).
- PM2.5 & PM10 concentrations: real-time measurement by portable devices twice at home and work sites.
- Blood inflammatory markers-platelet count, hsCRP and Fibrinogen
- Potential confounders: we shall collect informations on a range of potential confounders, including other air pollutants and traditional risk factors of atherosclerosis, entrusted to be controlled (stable).
Expected results: Adults after Montelukast treatment and exposed to high levels of PM2.5 or PM10 would have improved (increased) brachial FMD, and reduction of CIMT as compared with placebo. These will have great implication for comparative vascular epidemiology and development of preventive strategies.
详细描述
- Introduction Atherosclerosis related complications, in particular stroke and coronary artery disease, are the most important health issues in modernized societies, being the leading cause of death worldwide. In addition to traditional cardiovascular (CV) risk factors such as obesity, hypertension, dyslipidemia, diabetes mellitus, tobacco use and physical inactivity, particulate matter (PM) air pollution has been shown to be associated with cardiovascular morbidity and mortality in large epidemiological studies.[1-3] Long-term exposure to elevated PM levels can reduce life expectancy, especially particulate matter with an aerodynamic diameter <2.5um (PM2.5). Such PM has a causal relationship to cardiovascular morbidity and mortality.[1-4] An approximate 8-18% increase in cardiovascular mortality has been observed for every 10ug/m3 elevation in average PM2.5 exposure over the long term. [1. 3, 5] The biological mechanisms of atherogenic processes may involve direct effects of PM on cardiovascular system, and/or indirect effects mediated by oxidative stress and inflammation. [6-7] Far less research has been conducted so far on the contribution of PM to such long-term atherogenic processes in human populations. [1,2,8,9]
We have previously studied 1656 Chinese adults in southern and northern China in 1996 to 2007 with PM2.5 concentration ranging from 34 to 94 ug/m3. PM2.5 were significantly related to prognostic atherosclerotic surrogates i.e. brachial flow-mediated dilatation (FMD) and carotid intima media thickness (IMT), independent of traditional-risk factors.[10] Our CATHAY study supports a hypothesis that PM2.5 air pollution is strongly correlated with early atherosclerotic process in modernizing China.
Montelukast has been used successfully and proven safe for prevention of asthma episodes, supposed to be triggered by allergic-related inflammations of respiratory tract. Similar inflammatory process at lung and subsequently at blood vessels may be implicated in PM2.5-related accelerated atherosclerosis. [9]
- Aims and Hypotheses to be Tested: PM2.5 air pollution has been proven accelerating atherosclerotic process in Hong Kong and mainland China (CATHAY study). To further test this initial hypothesis, this interventional substudy aims
- To evaluate the impact of antiinflammatory agent Montelukast treatment on predictive atherosclerosis surrogates (FMD & IMT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •asymptomatic Chinese adults
- •aged 30-60 years with
- •concordant ambient PM2.5 exposure, both at home and at workplace.
排除标准
- •Those with family history of stroke, cardio-vascular disease
- •Hypertension with blood pressure >150/90 mmHg
- •Diabetics Mellitus
- •Overweight/ obesity (BMI >25kg/M2)
- •Cigarette smoking or ex-smoker <5 years
- •Known dyslipidemia defined as fasting LDL-C >4.1mmol/l and triglyceride >3.0 mmol/l.
- •Physical inactivity, with weekly leisure exercise less than 0.5 hour
- •Continuous usage of vitamins or herbal medicines in recent one year
研究组 & 干预措施
Montelukast
Montelukast 10mg daily (tablet) orally x 26 weeks
干预措施: Montelukast Oral Tablet (Drug)
Montelukast-matched placebo
Placebo (Montelukast identical) tablet 1 daily orally x 26 weeks
干预措施: Montelukast Placebo Oral Tablet (Drug)
结局指标
主要结局
Brachial flow-mediated dilation (FMD)
时间窗: At baseline and 26 weeks of interventional treatment
Changes in endothelial function (brachial FMD) in %
Carotid intima media thickness (CIMT)
时间窗: At baseline and 26 weeks of interventional treatment
Changes in carotid intima media thickness (CIMT) in mm
次要结局
- Changes of platelet count in k/uL(At baseline and 26 weeks of interventional treatment)
- Changes of hsCRP in mg/ml(At baseline and 26 weeks of interventional treatment)
- Changes of Fibrinogen in g/l(At baseline and 26 weeks of interventional treatment)
研究者
Kam Sang WOO
Adjunct Professor
Chinese University of Hong Kong