| Background and objectives:In China,the morbidity and mortality of cardiovascular disease(CVD)has been increasing,and about 3 million people annually die of CVD,accounting for about 41% of deaths from any cause.And the economic and social burden caused by CVD is enormous,which has become a major public health problem.This is mainly due to an increase in the number of people with cardiovascular risk factors(hypertension,hyperlipidemia,obesity,diabetes,smoking,etc.).Secondly,because of the aging of Chinese population,the morbidity and mortality of cardiovascular diseases in China may be greatly reduced if the risk factors of population can be detected as soon as possible,and the risk factors can be brought under control as soon as possible.Cardiovascular risk factors can increase the production of reactive oxygen species in vascular endothelial cells,and oxidative stress plays a key role in the occurrence and development of atherosclerosis.Oxidative stress has been found to accelerate telomere shortening.In recent years,foreign studies have shown that peripheral blood telomere length may be associated with acute coronary syndrome(ACS),but the correlation is significant among different ethnic groups.Considering that the previous study population mainly came from abroad,we did not see the relationship between telomere length and cardiovascular risk factors in Chinese.This study is intended to explore the relationship between the two in Chinese Han population.In order to find out a simple and easy way to predict and evaluate the severity of acs biological markers for the understanding of the pathogenesis of atherosclerosis to provide a new basis.The presumption that telomere dysfunction may affect mitochondrial function is present in animal experiments and the correlation between telomere length and mitochondrial DNA(mtDNA)copy number in human studies is also confirmed among people with mental disorders or normal.This study intends to explore the relationship between telomere length and mtDNA copy number in acs patients,controls and subgroups of cardiovascular risk factors,so as to understand the relationship between the changes of telomere function and mitochondrial function and atherosclerosis,which is helpful to further explore the pathogenesis of atherosclerosis at the gene level.Objective:1.Probe into the relationship between telomere length in peripheral blood leukocytes and acute coronary syndrome in Chinese Han population.2.Study on the relationship between telomere length and mtDNA copy number in acs patients,controls and subgroups of cardiovascular risk factors.3.To explore the relationship between telomere length and cardiovascular risk factors in Chinese Han population.4.To explore the difference of telomere length and mtDNA copy number before and after follow-up.Methods:1.On the premise of obtaining the informed consent of the object of study,581 patients admitted to Department of Cardiology and Coronary Angiography in the first affiliated Hospital of Air Force military Medical University was included.2.Collect the peripheral arterial blood and measure telomere length and mtDNA copy number of peripheral leukocytes by real-time quantitative PCR.All the subjects were examined by coronary angiography.Based on the results of coronary angiography,Gensini score was calculated to evaluate the severity of coronary artery stenosis in each of the subjects.Finally,according to the quartile interval of Gensini score,the subjects were divided into four groups.3.Information on age,sex,body weight,body mass index,smoking history,hypertension history,diabetes history and biochemical data were collected.The cardiovascular risk factors of the subjects were comprehensively evaluated by Framingham risk factor score.4.The average follow-up period was 2.5 years,and the standard anti-atherosclerosis therapy was performed during the follow-up period.Telomere length and mtDNA copy number were measured again in 33 patients with the same method.Finally,the difference of telomere length and mtdna copy number before and after follow-up was compared with self-control method.5.The test data were analyzed with SPSS 19.0 software,including the difference of telomere length between ACS group and Control group,the difference of telomere length among four groups in Gensini score,the correlation between telomere length and Gensini score,the OR values of ACS for short telomere,the correlation between telomere length and mtDNA copy number,the difference of telomere length and mtDNA copy number before and after follow-up.Results:1.The telomere length differences between ACS group and control group and among Gensini score groups: According to the results of coronary artery angiography,the subjects(n=581)were divided into ACS group(n=417)and control group(n=164).telomere length in ACS group was significantly higher than that in control group(median 1.06,0.19-26.95 vs 1.22,0.30-11.84,P<0.01).According to the four quantile interval of Gensini score results,the study population(n=581)was divided into 0-20.5(first quartile,n=145),20.5-54(second quartile,n=147),54-89(third quartile,n=146),89-254(fourth quartile,n=143).There was significant difference in telomere length among four groups in Gensini score(median 1.17,0.30-11.84 vs 1.15,0.42-17.21 vs 1.06,0.21-12.71 vs 1.01,0.19-26.95,P<0.01)and telomere length was negatively correlated with Gensini score(r=-0.16,P<0.001).2.The relationship between telomere length and ACS risk: When subjects were divided into long and short groups based on the median telomere length in controls,subjects with short telomere length had a significantly increased ACS risk(adjusted OR,1.524;95%CI,1.046-2.220;P<0.05)compared to those with long telomere length.Moreover,when subjects were divided into longest tertile,middle tertile and shortest tertile groups based on the tri-sectional quantile of telomere length in all individuals,subjects with middle and shortest telomere length had a significantly increased ACS risk(middle tertile: adjusted OR,1.820;95%CI,1.097-3.018,P<0.05;shortest tertile: adjusted OR,1.695;95%CI,1.011-2.843,P<0.05)compared to those with longest telomere length.3.The relationship between telomere length and cardiovascular risk factors: According to the tri-sectional quantile of Framingham risk factor score,the study subjects were divided into three groups: low risk group(1-12),moderate risk group(12-15)and high-risk group(15-22).There was no significant difference in telomere length among the three groups.Moreover,there was no significant difference in cardiovascular risk factors among different telomere length groups(>1.34,0.88-1.34,<0.88).4.The difference of telomere length and mtDNA copy number before and after follow up: the study subjects were followed up for an average of 2.5 years,of which 33 patients with interventional therapy received follow-up data.The results showed that telomere length was significantly longer than that before operation.The difference was statistically significant(P<0.01),but there was no significant difference in mtdna copy number before and after follow-up(P> 0.05).5.The relationship between telomere length and mtDNA copy number: In all individuals,telomere length was positively correlated with mtDNA copy number(r=0.6,P<0.001).There was a significant positive correlation between the two in ACS group(r=0.691,P<0.001)and control group(r=0.224,P<0.01).In the traditional cardiovascular risk factors groups,telomere length and mtDNA copy number also have correlation: elder(>60y)(r=0.311,P<0.01),male(r=0.648,P<0.001),female(r=0.254,P<0.01),smokers(r=0.741,P<0.001),non-smokers(r=0.232,P<0.001),hypertensive subjects(r=0.292,P<0.001),normotensive subjects(r=0.239,P<0.001),nondiabetic subjects(r=0.266,P<0.001).Conclusion:1.The shorter telomere length in peripheral blood leukocytes,the more severe coronary artery stenosis,and the shorter telomere length reflects increased risk of acute coronary syndrome.2.The telomere length of peripheral blood leukocytes was significantly prolonged after 2.5 years of standardized treatment.3.The telomere length of peripheral blood leukocytes was positively correlated with mtDNA copy number in ACS patients,controls and subgroups of cardiovascular risk factors. |
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