Association Between Subclinical Hypothyroidism And Prognosis Of Elderly Patients After Percutaneous Coronary Intervention And Its Risk Factors

Coronary artery disease is one of the most common causes of death in elderly patients.Its incidence increases significantly with increasing age.Percutaneous coronary intervention(PCI)is an effective treatment for coronary artery disease,but the mortality of elderly patients after PCI is still significantly higher than that of young patients.Researchs have demonstrated that hypothyroidism can lead to atherosclerosis,but whether subclinical hypothyroidism(SCH)contributes to increased mortality in elderly patients with coronary artery disease has not been established.It’s a challenging task for clinicians to predict the probability of death after PCI.Therefore,we further studied the influencing mechanism of hypothyroidism on atherosclerosis,assessed the impact of SCH on mortality in elderly patients aged 65 years or older who underwent PCI,and identified the risk factors affecting mortality in these patients.Part One Study on the correlation between hypothyroidism and arteriosclerosis in ratsObjective: To study the levels of inflammatory factors in hypothyroidism rats and explore the relationship between them and arteriosclerosis in rats.Methods: Thirty healthy male SD rats were selected and randomly divided into hypothyroidism group and control group with 15 rats in each group.Hypothyroidism group was given propylthiouracil(3mg/kg/d)by gavage.The control group was given equal volume of normal saline by gavage.Peripheral blood was extracted to detect the changes of total triiodothyrogenine(TT3),free triiodothyrogenine(FT3),total thyroxine(TT4),free thyroxine(FT4),thyrotropin stimulating hormone(TSH),triglyceride,total cholesterol,low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)after continuous gavage for 10 weeks.The weight of SD rats in each group was accurately weighed.Body surface electrocardiogram(ECG)was measured after anesthesia,and heart rate and waveform changes of each group were recorded.Fresh myocardial tissue and aorta were collected for pathological specimens and western blotting experiments before the rats were sacrificed.Results:1.After 10 weeks of feeding,the average body weight of hypothyroidism group was significantly lower than that of control group,which suggesting growth retardation.TT3,FT3 and TT4 levels in hypothyroidism group were lower than those in control group,and TSH level was higher than control group,which suggesting hypothyroidism group was successful in modeling.The triglyceride level of hypothyroidism group were lower than those of control group,while there was no statistical difference in total cholesterol,HDL-C and LDL-C between the two groups.2.The mean heart rate(313.34±83.60 beats/min)in the hypothyroidism group was significantly lower than that in the control group(372.75±17.68beats/min).Ecg showed ST segment depression was more significant in the hypothyroidism group than in the control group.3.The expressions of nuclear factor-κB(NF-κB),tumor necrosis factor(TNF)-α and interleukin(IL)-6 in hypothyroidism group were significantly increased compared with control group.4.Compared with the control group,the myocardial vascular wall in hypothyroidism group was thickened,collagen fibers were hyperplasia,the aortic intima was thickened and fibrosis was aggravated.Conclusions:1.Compared with the control group,the heart rate of hypothyroidism rats slowed down and myocardial ischemia aggravated.2.The expression of NF-κB,TNF-α and IL-6 increased in hypothyroidism rats.3.Compared with the control group,the hyperplasia of smooth muscle cells and collagen fibers in myocardium vessels and aorta of hypothyroidism rats resulted in abnormal vascular structure.Part Two The impact of subclinical hypothyroidism on long-term outcomes in elderly patients undergoing percutaneous coronary interventionObjective: The purpose of this study was to evaluate the association between SCH and long-term outcomes in elderly patients undergoing PCI.Methods: Patients aged 65 years or older who underwent PCI and thyroid function examination were included.The inclusion criteria were as follows:(1)diagnosis of stable angina pectoris(SAP),unstable angina pectoris(UAP)and acute myocardial infarction(AMI);(2)Age≥65 years;(3)Underwent PCI;(4)Thyroid function examination.Clinical data were obtained from the inpatient medical records,including general medical history,past medical history,examination of thyroid function and coronary intervention data.Patients were divided into SCH group and euthyroidism(ET)group based on thyroid function test.They were prospectively followed up for4 years after enrollment.The patients were followed up by telephone or outpatient and the contents were death,cardiac death and medication after enrollment.The endpoints were death.Cox proportional hazard regression analyses were used to estimate the hazard ratio(HR)of all-cause death and cardiac death for patients with SCH during a 4-year follow-up period.Results:1.The rate of loss to follow-up was 3.26%,and the final cohort included3168 elderly patients underwent PCI,of whom 10.1%(n=320)had SCH and89.9%(n=2848)had euthyroidism(ET).SCH was more common in women and hyperlipidemia than in ET patients,with higher body mass index(BMI),serum total cholesterol,triglycerides and LDL-C.However,the levels of hemoglobin and HDL-C in SCH patients were lower than those in ET patients.There was no significant difference between the two groups in the number of pathological vessels,distribution of target vessels and the number of stent implantation.2.The 4-year cumulative all-cause mortality and cardiac mortality of all patients were 7.17% and 3.91% respectively.The cumulative 4-year all-cause mortality was 9.1% in SCH and 7.0% in ET,respectively.The 4-year cumulative cardiac mortality was 5.0% and 3.8%,respectively.Kaplan-meier analysis showed no significant differences in all-cause and cardiac mortality between SCH and ET patients.3.Cox proportional hazard model analysis showed that SCH was not associated with an increased risk of all-cause or cardiac death compared with ET.Conclusions: SCH at admission was not associated with an increased risk of all-cause death or cardiac death in elderly patients underwent PCI.SCH did not represent a risk factor for mortality in patients aged 65 years or older who underwent PCI.Part Three Risk factors analysis of death after percutaneous coronary intervention in elderly patientsObjective: To investigate the risk factors of death in patients aged 65 years or older with coronary artery disease who underwent PCI,so as to provide evidence for secondary prevention.Methods: The data of elderly patients with coronary artery disease underwent PCI was retrospectively analyzed.The inclusion criteria were as follows:(1)Diagnosis of SAP,UAP or AMI;(2)Age ≥ 65 years;(3)Receiving PCI treatment.Patients with myocardiopathy,severe cardiac valvular disease requiring surgical treatment,valve replacement,malignant tumor,immune system disease,connective tissue disease and incomplete clinical data were excluded.Clinical data were obtained from the inpatient medical records,including general medical history,past medical history,laboratory examination and coronary intervention data.The patients were prospectively followed up for 4 years after enrollment.They were followed up by telephone or outpatient and the contents were death and cardiac death after enrollment.The endpoints were all-cause and cardiac death.Cox proportional hazard regression analyses were used to estimate the hazard ratio of all-cause death and cardiac death for patients during a 4-year follow-up period.Results:1.The rate of loss to follow-up was 5.42%,and the final cohort included1782 elderly patients underwent PCI.The mean age of the patients was 70.98±4.25 years,and 57.18% of whom were male.The prevalence of hypertension was the highest,and the main diagnosis was UAP.The coronary artery lesions were mainly single-vessel lesions.The most easily involved vessels were anterior descending artery,then right coronary artery,circumflex artery and left main artery.2.The 4-year cumulative all-cause mortality were 8.87%.The proportion of male,hypertension,diabetes,UAP,creatinine level and mean number of stents implanted were higher in death group than the non-death group.3.The 4-year cumulative cardiac mortality were 4.04%.The proportion of hypertension,SAP,double vessel disease,creatinine level and number of stents were higher in cardiac death group than in non-cardiac death group,while the proportion of UAP,single vessel disease and left ventricular ejection fraction(LVEF)level were lower in cardiac death group than in non-cardiac death group.4.After adjusting for age,gender,medical history,laboratory examination,diagnosis and the characteristics of coronary artery disease,hypertension,diabetes,smoking and the number of stents implanted were independent risk factors for all-cause death in elderly patients underwent PCI,while LVEF was a protective factor.Hypertension,triglyceride were independent risk factors for cardiac death in elderly patients underwent PCI,while LVEF were protective factors.Patients diagnosed with UAP had a lower risk of cardiac death than those diagnosed with SAP.Conclusions: Hypertension,diabetes,smoking and the number of stents implanted were independent risk factors for all-cause death in elderly patients underwent PCI,while LVEF was a protective factor.Hypertension,triglyceride were independent risk factors for cardiac death in elderly patients underwent PCI,while LVEF were protective factors.Patients diagnosed with UAP had a lower risk of cardiac death than those diagnosed with SAP.