This study aimed to explore underlying mechanisms of individual differences in drugs for coronary heart disease treatment and its association with adverse consequences. It will enroll approximately 4000 coronal heart disease patients aged between 18 and 80 years in mainland China and follow-up for at least 1 years. Questionnaires, anthropometric measures, laboratory tests, and biomaterials will be collected . The principal clinical outcomes of the study consist of ischemia attack , cardiac death, renal injury,and myotoxic activity.
The study is a multicenter prospective cohort study, aimed to explore underlying mechanisms of individual differences in drugs for coronary heart disease treatment and its association with adverse consequences.The genomic genotype, DNA methylation and metabolome of 1000 patients with coronary heart disease were determined using illumina high-density genotyping chip, high-throughput sequencing and high-resolution mass spectrometry. Blood exposures of statins and metoprolol and its metabolites was determined by UPLC-MS/MS. The biological network using cross-omics analysis was reconstructed to identify potential causative key genes, bacteria, and endogenous metabolite targets that cause differences in individual responses. A machine identification algorithm selecting clinical factors and multi-omics targets was used to establish a predictive mathematical model. A multi-center clinical cohort of 3000 coronal heart disease patients was used to verify the effects of various levels of omic targets on drug blood exposures, efficacy and toxic side effects. A comprehensive model based on multi-target combination of individualized drugs was constructed, and the predictive effect was clinically analyzed.
Study Type
OBSERVATIONAL
Enrollment
4,000
During the follow-up period,general information(age, sex, BMI, blood pressure, the history of drink and smoke, medical history, etc).Blood biochemistry parameters（Lipid, hsCRP levels, etc）and other laboratory examination parameters will be collected
Genome-wide genotype , DNA methylation and metabolomes were determined using illumina high-density genotyping chips, high-throughput sequencing, and high-resolution mass spectrometry respectly. Blood exposure of statins and metoprolol and its metabolites was determined by UPLC-MS/MS.
The genome-wide genotype of patients with coronary heart disease was detected using the illumina chip. The methylation level of the functional region was detected by the target region enrichment methylation sequencing method. Intestinal flora differences were detected using 16SrDNA high-throughput sequencing.
Guangdong General Hospital
Guangzhou, Guangdong, China
RECRUITINGThe First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGXiangYa Hospital Central South University
Changsha, Hunan, China
Death
All-cause death
Time frame: from date of baseline examination until the date of first documented death,up to 48 months
MACE
MACE was defined as the occurrence of cardiac death, nonfatal myocardial infarctions, coronary revascularisation and cerebral infraction.
Time frame: from date of baseline examination until the date of first documented cardiovascular events,up to 48 months
Bleeding
Bleeding was the six-month incidence of combined alarming, internal, and nuisance bleeding events defined according to Serebruany et al15. Alarming bleeding included bleeding requiring a transfusion, intracranial bleeding, and life-threatening bleeding. Internal bleeding included haematoma, epistaxis, blood loss from the mouth, vagina, melaena, eye bleed, haematuria, and haematemesis. Nuisance bleeding included easy bruising, bleeding from small cuts, petechiae, and ecchymosis.
Time frame: from date of baseline examination until the date of first documented bleeding,up to 48 months
Statin-induced myopathy (SIM)
The definition of SIM from statin treatment was based on the patients' subjective sense of muscular pain as well as CK elevations. These muscular side effects included myalgia (muscle pain/ache without serum CK elevations), other muscle-related symptoms such as weakness, cramps, spasms, soreness and twitching, CK elevations without physical symptoms, myositis or other muscle symptoms with CK elevations, and rhabdomyolysis.
Time frame: from date of baseline examination until the date of first documented SIM,up to 48 months
CI-AKI
CI-AKI was diagnosed if a patient had an absolute increase in serum creatinine (sCr) concentration ≥ 0.3 mg/dl (26.4 μmol/L) from baseline or a relative increase ≥ 50 % in sCr concentration for more than 6 h within 48 h after surgery
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Machine learning algorithms such as multiple linear regression or Bayesian classification are used to optimize clinical factors and multi-group targets to establish predictive mathematical models.
Renji Hospital Affiliated to Shanghai Jiaotong University
Shanghai, Shanghai Municipality, China
RECRUITINGWest China Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGTime frame: more than 6 h within 48 h after Coronary Angiography