Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04864457 |
| Other study ID # |
Young-COSMOS.001 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
July 31, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
Shenzhen People's Hospital |
| Contact |
Xin Sun, MD |
| Phone |
+86-755-22943205 |
| Email |
sunxinflying[@]163.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
With the rapid development of China's economy, changes in diet structure, lifestyle and
excessive mental pressure have led to a younger trend in the incidence of ACUTE coronary
syndrome, and the mortality rate has been on the rise, especially in Shenzhen, the country
with the youngest average age.Coronary heart disease among young people not only reduces the
quality of life and loses the ability to work, but also prematurely consumes medical
resources and increases social costs, bringing heavy burdens to families and
society.Therefore, it is of great significance to conduct researches on the transcription,
metabolism and microbiome of young patients with ACUTE coronary syndrome and obtain the
multi-group characteristics of these patients for early warning, guiding the improvement of
life style, regulating treatment, improving treatment rate, and reducing family and social
burden.
Description:
1. Research purpose and significance In recent years, with the rapid development of China's
economy, the changes in dietary structure and lifestyle, as well as excessive mental stress,
and other factors have led to an obvious trend of younger incidence of Coronary artery
disease (CAD), and an increase in the death rate.This is especially true in Shenzhen, which
has the youngest average age in the country.CAD in young people not only reduces the quality
of life and loses the ability to work, but also prematurely consumes medical resources,
increases social costs, and brings heavy burden to families and society.Therefore, it is of
great significance to study the transcriptome, metabolome and intestinal flora of young CAD
and obtain the multiomic characteristics of these patients for early warning, guiding the
improvement of lifestyle, regulating treatment, improving treatment rate, and reducing the
burden of family and society.
2. Research status at home and abroad
1. The public health burden of coronary artery disease in China With the development of
social economy, China's national lifestyle has undergone profound changes. Under the
social background of population aging and urbanization, the risk of Atherosclerotic
cardiovascular disease (ASCVD) is increasing day by day.The incidence of cardiovascular
diseases continues to increase.ASCVD is the number one cause of death in China,
surpassing cancer and other diseases.CAD is an important part of ASCVD. According to
China Cardiovascular Health and Disease Report 2019, the total number of CAD patients in
China is about 11 million.CAD causes extremely high mortality and disability rate,
causing serious public health burden and social and economic burden.The 5th Chinese
health service survey in 2013 showed that the prevalence rate of coronary artery disease
among residents ≥15 years old was 12.3‰ in urban areas, 8.1‰ in rural areas, and 10.2‰
in urban and rural areas.According to China's Health Statistics Yearbook 2018, the
mortality rate from coronary artery disease was 115.32 per 100,000 urban residents and
122.04/100,000 rural residents in 2017.Based on the sample database of inpatients
insured by China's basic medical insurance from 2010 to 2014, the annual hospitalization
rate of acute myocardial infarction was estimated to be 44.2/100,000.The median
hospitalization cost for patients with acute myocardial infarction in urban China is
31,000 yuan, and the median hospitalization cost for patients receiving coronary
intervention therapy is 52,000 yuan.
It is an indisputting fact that CAD causes serious social burden. How to let more CAD
patients find their disease as early as possible, intervene as early as possible, and
avoid returning to poverty, becoming disabled or even dying due to disease due to the
aggravation of disease is an urgent public health problem.According to the Healthy China
2030 Plan, the premature mortality rate from major chronic diseases is expected to drop
from 18.5% in 2015 to 15.9%, indicating that the management of chronic diseases is also
being increasingly emphasized at the national health policy-making level.
2. Epidemiological characteristics of coronary heart disease in young people With the
improvement of diagnosis and treatment level and people's attention to CAD, the case
fatality rate of CAD in the world has decreased significantly.Epidemiological data in
the United States showed that from 1980 to 2002, the mortality rate of male and female
CAD patients decreased by 52% and 49% respectively [3].Unfortunately, improvements in
CAD outcomes have not covered all age groups.Epidemiological data from the United States
[3], the United Kingdom [4], Canada [5] and Australia [6] all show that the morbidity
and mortality of young CAD patients younger than 45 years old are increasing year by
year.The research group also confirmed in the previous study that the proportion of
young CAD patients admitted to the Department of Cardiology of Shenzhen People's
Hospital increased year by year from 2015 to 2019.This shows that young CAD patients
have different disease development characteristics, and the theory and basis of young
CAD are derived from the study of the whole population, and the corresponding innovation
of treatment concept has not significantly improved the prognosis of young CAD
patients.Therefore, it is of great significance to promote the research of youth CAD,
reveal the pathogenesis of youth CAD, and explore the prediction, diagnostic markers and
therapeutic targets for the prevention and treatment of youth CAD and the improvement of
national health level.
Compared with the general population, young CAD patients are often associated with
multiple risk factors.According to statistics, more than half of the young people aged
18-24 have at least one CAD risk factor [9, 10], and nearly 1/4 of the young people have
atherosclerotic plaques. The size and range of atherosclerotic plaques are directly
positively correlated with the number of risk factors.Poor diet, overweight,
hyperlipidemia, physical inactivity, and smoking are the major risk factors for young
adults, and the number of risk factors is closely related to long-term
outcomes.Ignorance of relevant risk factors in young people further increases the risk
of CAD, and once coronary atherosclerotic plaque forms, the condition continues to
progress to coronary artery disease, which will seriously affect the quality of life and
life expectancy of young patients [11-13].However, at present, there are very few
researches on the mechanism behind the special epidemiological phenomenon of CAD in
young people [7, 8], and corresponding researches are urgently needed to explain the
pathogenesis of this unique CAD population.
3. Dynamic pathological changes of coronary artery disease CAD is a chronically
progressive, dynamically changing pathological process that can be in a long-term stable
state or become unstable at any time. Plaque rupture or erosion can cause acute
thrombotic events.According to clinical manifestations, CAD can be divided into Acute
coronary syndrome (ACS) and Chronic coronary syndrome (CCS).
ACS is a group of clinical syndromes characterized by acute myocardial ischemia,
including ① unstable angina pectoris (UA);② Acute non-ST segment elevation myocardial
infarction (NSTEMI);③ Acute ST-segment elevation myocardial infarction (STEMI).The main
mechanism is the rupture or erosion of coronary atherosclerotic plaque combined with
thrombosis and/or vasospasm, which causes the sharp aggravation of coronary artery
stenosis or acute occlusion.
CCS covers the different developmental stages of CHD in addition to the clinical
manifestations dominated by acute coronary thrombosis, including asymptomatic myocardial
ischemia, vasospasm, and microcirculatory lesions.The six most common CCS clinical
conditions include: (1) patients with suspected coronary heart disease and "stable"
angina pectoris, with or without dyspnea;② patients with newly emerged heart failure or
left ventricular dysfunction, suspected of CAD;③ Patients with asymptomatic or stable
symptoms within 1 year after ACS, or patients with recent revascularization;(4) Patients
with or without symptoms at least 1 year after initial diagnosis or revascularization;⑤
patients with angina pectoris, suspected vasospasm or microcirculation diseases;(6)
Asymptomatic patients with coronary heart disease were found during screening.
The dynamic pathological process of CAD has become the focus of current research, and
every link in the pathophysiological process may become a potential new target for
prevention and treatment.
4. Research status of transcription, metabolism and intestinal flora of coronary artery
disease Recent studies have shown that CAD is associated with changes in intestinal
microbiota in different populations, and metabolites of intestinal microbiota are
considered to be major markers of heart damage.Koren et al. found that the
atherosclerotic plaques contained DNA sequences of bacteria such as Staphylococcus
aureus, Veroncoccus and Streptococcus, which could also be observed in the plaques of
the intestinal vessels of the same individual.Liu et al. conducted multi-omics analysis
on 161 CAD patients and 40 healthy controls, and found that the composition of
intestinal flora and metabolites significantly changed with the severity of CAD.These
studies suggest that intestinal flora can influence the dynamic pathological process of
CAD by regulating the metabolic pathways of the host.
Some special non-coding RNA molecules, such as circRNAs (Circularrnas) and Long
non-coding RNAs (lncRNAs), were abnormally expressed during the development of CAD and
had certain regulatory functions.As a biomarker and therapeutic target, it plays an
important role in the diagnosis and treatment of CAD.At the same time, previous
transcriptome analysis of a variety of atherosclerotic cells, animal and human vascular
tissues revealed that a large number of genes were expressed abnormally during the
pathological process of CAD [1-7], suggesting that these genes may be involved in the
pathological process of CAD, but whether these genes are susceptible genes for young CAD
remains unclear.
5. Our project ideas CAD in young people imposes a heavy burden on families and
society.Young CAD has its own characteristics of the disease, and the elderly patients
are different, smoking, drinking, staying up late and other bad lifestyle, as well as
unreasonable diet, work pressure is more common in young CAD patients.Previous omics
studies on CAD were conducted in the whole population and could not accurately reveal
the pathogenesis of the young population.Therefore, only by studying the transcriptome,
intestinal flora and metabolism of young CAD, revealing its pathogenesis and exploring
new biomarkers and therapeutic targets, can we fundamentally solve the problems of young
CAD and provide effective strategies for clinical prevention and treatment of young CAD.
This topic proposed line selected 18 to 45 years old coronary interventional diagnosis and
treatment of 200 patients, according to the results of coronary angiography and clinical
manifestations of divided into young patients with normal coronary group (40 cases), the
young patients with chronic coronary syndrome group (80 cases) and youth group (80 cases),
acute coronary syndrome patients to metabolism of the full spectrum of blood group and the
whole transcriptome sequencing,And intestinal microflora metagenome and full spectrum
metabolome sequencing of feces.
