| Background Coronary Artery Disease(CAD),is an ischemic heart disease caused by stenosis or blockage due to the accumulation of plaque in the coronary arteries.As of 2019,there are approximately 197 million patients with CAD worldwide.The prevalence and death toll increases every year,causing enormous pressure and burden on the health care system.The pathogenesis of CAD is sophisticated,and the influence of a lot of risk factors cannot be ignored.It will be helpful to develop and improve relevant preventive measures and treatment strategies,as well as to reduce the incidence and morbidity and mortality by exploring the co-causal association between noninfectious diseases and CAD.Objectives(1)To sort out the research evidence on the association between noninfectious diseases and CAD and the relationship between diseases,and to clarify the current conclusion of research in related fields.(2)To determine whether there is a causal relationship on the genetic level between non-infectious diseases involved in current research that may be associated with CAD,and to provide more comprehensive and accurate guidance on a genetic level for the prevention and treatment of CAD.Methods(1)Overview of Reviews: eight databases,including Chinese Biomedical Literature Database,China National Knowledge Infrastructure,Wanfang Data Platform,CQVIP,Pub Med,Embase,Cochrane Library and Web of Science,were systematically searched.The results were screened and systematic reviews/metaanalyses exploring the association between non-infectious diseases and CAD were included.The basic information,exposure factors and meta-analysis-related information were collected.The methodological quality was assessed using A Measure Tool to Assess Systematic Reviews-2(AMSTAR-2).The results of included research were synthesized qualitatively on the association between non-infectious diseases and CAD.(2)Mendelian Randomization: the verification of selected non-infectious disease risk factors based on three hypotheses of relevance,exclusivity and independence,using publicly available data resources from the Genomic Wide Association Study.The causal effect between exposure and outcome was estimated using Inverse Variance Weighted(IVW),MR-Egger,Maximum Likelihood,Weighted Median,and Simple Mode.Data quality was controlled by Cochran’s Q test and p-statistic for heterogeneity,MR-Egger intercept test for horizontal multi-effects analysis,and leave-one-out method for sensitivity analysis.Results(1)Overview of Reviews: 61 systematic reviews/meta-analyses were included after removing duplication and screening,including 46 SRs in English and 15 SRs in Chinese.The included research was published between 1994 and 2022,and the types of included studies were cohort studies,case-control studies,and cross-sectional surveys.Quality evaluation results showed that overall methodological quality was moderate.The included studies focused on 19 different non-infectious diseases,among which hypertension,diabetes,obesity,hypercholesterolemia and metabolic syndrome were significantly associated with CAD.There was a correlation between CAD and sleep apnea syndrome,asthma,subclinical hypothyroidism,periodontal disease,erectile dysfunction,depression,anxiety,polycystic ovary syndrome,primary Sjogren’s syndrome,idiopathic inflammatory myopathy and inflammatory bowel disease;there is no significant evidence that subclinical hyperthyroidism,systemic lupus erythematosus,and age-related macular degeneration were associated with CAD.(2)Mendelian Randomization: there is no available data from g Genomic Wide Association Study for idiopathic inflammatory myopathy,and the information on genetic exposure to CAD for hyperthyroidism,periodontal disease,erectile dysfunction,anxiety,polycystic ovary syndrome,and primary Sjogren’s syndrome were insufficient.Two-sample Mendelian Randomization study was conducted for the remaining 12 noninfectious diseases with co-morbid causal associations to CAD in a many-to-one sample.The results showed that hypertension(IVW β=1.686,95% CI 1.375 to 1.997,p<0.00001),diabetes(IVW β=2.661,95% CI 1.446 to 3.876,p=0.00002),obesity(IVWβ=0.153,95% CI 0.095 to 0.212,p< 0.00001),hypercholesterolemia(IVW β=0.444,95% CI 0.307～0.582,p<0.00001),metabolic syndrome(IVW β=0.641,95% CI0.407～0.874,p<0.00001),hypothyroidism(IVW β=1.013,95% CI 0.428 to 1.597,p=0.00068)and depression(IVW β=0.137,95% CI 0.035 to 0.239,p=0.00855)could contribute to the development of CAD as independent risk factors;systemic lupus erythematosus(IVW β=0.021,95% CI 0.004 to 0.038,p=0.01584),age-related macular degeneration(IVW β=-0.031,95% CI-0.091～0.028,p=0.30074),sleep apnea syndrome(IVW β=0.043,95% CI-0.139～0.226,p=0.64185),asthma(IVW β=-0.013,95% CI-0.072～ 0.047,p=0.67553)and inflammatory bowel disease(IVW β=-0.012,95% CI-0.04 to 0.015,p=0.38350)were not causally associated with CAD.Conclusions:(1)Both overview of reviews and mendelian randomization studies supported that hypertension,diabetes,obesity,hypercholesterolemia,and metabolic syndrome,as major risk factors for CAD,had causal relationships with CAD.(2)Overview of reviews showed that sleep apnea syndrome,asthma,subclinical thyroid dysfunction,erectile dysfunction depression,anxiety,polycystic ovary syndrome,primary Sjogren’s syndrome,idiopathic inflammatory myopathy and inflammatory bowel disease were associated with the development of CAD and no association was found between systemic lupus erythematosus,age-related macular degeneration and CAD.(3)The results of the mendelian randomization study confirmed that there was a causal relationship existed between subclinical hypothyroidism,depression and CAD,and no causal relationship between sleep apnea syndrome,asthma,systemic lupus erythematosus,age-related macular degeneration,and inflammatory bowel disease and CAD.(4)The association between sleep apnea syndrome,asthma,inflammatory bowel disease and coronary heart disease co-morbidities observed in observational studies may be due to confounding factors or reverse causation. |
PDF Full Text Request