The Interaction Of LP(a) And Traditional Cardiovascular Risk Factors In Coronary Artery Disease Of Myocardial Infarction

Research Background:In recent years,a large amount of research evidence has accumulated evidence of the association between lipoprotein(a)(LP(a))with atherosclerosis and arterial thrombosis.However,there is currently a lack of suitable methods for reducing LP(a),drugs that take into account efficacy and safety are being developed and explored,and there is a view that groups with elevated LP(a)can reduce the risk of disease by controlling other risk factors,but this statement is controversial and needs more theoretical and clinical practice to support.It is worth noting that most of the current articles on this issue do not mention the calculation of interactions,which allow us to know whether the combined impact of two risk factors on the disease exceeds the sum of their individual effects on the disease.Objective:This study took the degree of coronary artery stenosis in patients with acute myocardial infarction(AMI)as the research outcome,explored whether there is an additive interaction between LP(a)and traditional risk factors,and analyzed the possible mechanisms,in order to provide a certain basis for reducing the risk of LP(a)disease by controlling other risk factors,the calculation of interactions can also assist us in further stratifying high-risk groups of coronary artery disease in clinical practice.Methods:A retrospective analysis was performed on patients who were first diagnosed with AMI and coronary angiography at the First Affiliated Hospital of Dali University from July 2020 to July 2022.General clinical data,laboratory data,imaging indicators and coronary angiography records of the study subjects were collected.First,the basic data analysis included general clinical data comparison between the LP(a)elevated group and the LP(a)normal group,and the general clinical data comparison grouped according to Gensini score.Then,ordered logistic regression was used to screen out independent risk factors for the degree of coronary artery stenosis.Finally,the risk factors for coronary artery disease were subgrouped,the risk of LP(a)in each subgroup was calculated,and the relative excess risk of interaction(RERI),the percentage of attributable proportion of interaction(AP),the synergy index(SI)and the confidence interval of the three were calculated to determine whether LP(a)and traditional cardiovascular risk factors had additive interaction in coronary artery lesions of myocardial infarction.Results:1.LP(a)was skewed distribution in the included AMI population,accounting for 38% of the increase.The prevalence of non-HDL-C,B-type natriuretic peptide(BNP),Gensini score,and cervical vascular plaque was higher in the group with elevated LP(a)than in the normal LP(a)group,and the difference between the groups was statistically significant(P<0.05).2.The study subjects were divided into G1-G4 group from low to high according to the Gensini score value by quartile method.The levels of age,LDL-C,BNP,LP(a),TC,non-HDL-C,Apolipoprotein B(Apo-b),white blood cells and platelets in the highest quartile group were higher,and the ejection fraction was lower.The difference between the groups was statistically significant(P<0.05).The proportion of hypertension,diabetes,smoking and obesity in the highest quartile group was higher,and the difference between the groups was statistically significant(P<0.05).3.In the multivariate ordered logistic regression analysis,LDL-C,non-HDL-C,LP(a),hypertension,diabetes,smoking,obesity,and age were independently correlated with the degree of coronary artery stenosis(P<0.05).4.Taking the degree of coronary artery stenosis as the dependent variable,after multifactorial correction,the risk of severe coronary artery stenosis caused by increased LP(a)increased with the increase of LDL-C level,and the OR(95% CI)of groups 1-5 were 2.117(1.039-4.313),2.050(1.302-3.227),2.157(1.368-3.403),3.038(1.532-6.025),5.914(2.051-17.056),respectively;with the increase of non-HDL-C levels,the risk of severe coronary artery stenosis due to elevated LP(a)increased,and the OR(95% CI)in groups 1-4were 1.886(1.237-2.874),1.900(1.092-3.304),2.474(1.334-4.587),4.278(2.227-8.216),respectively;compared with the non-hypertensive group,the risk of severe coronary artery stenosis due to elevated LP(a)in the hypertensive group was greater,OR(95% CI)were 1.911(1.318-2.769)and 3.703(2.560-5.358),respectively;compared with the non-diabetic group,the risk of severe coronary artery stenosis due to elevated LP(a)in the diabetes group was greater,OR(95% CI)were 2.000(1.487-2.961)and 3.743(2.028-6.909),respectively;elevated LP(a)was comparable in the non-smoking and smoking groups with a comparable risk of severe coronary artery stenosis,OR(95% CI)were 2.185(1.403-3.403)and 2.182(1.561-3.048),respectively;elevated LP(a)was comparable in the non-obese and obese groups with a comparable risk of severe coronary artery stenosis,OR(95% CI)were2.163(1.626-2.877)and 2.197(1.044-4.622),respectively.5.Taking the degree of coronary artery stenosis as the dependent variable,after multifactor correction,the risk of severe coronary artery lesions when high LP(a)combined with high LDL-C,high non-HDL-C,hypertension,diabetes,smoking,and obesity was significantly increased than when the risk factors existed alone.Further calculation of RERI,SI,AP and the three confidence intervals showed that LP(a)had positive additive interaction with LDL-C,non-HDL-C,hypertension and diabetes,RERI(95% CI)were 6.059(2.195-9.922),3.606(1.279-5.932),4.614(2.144-7.070),3.089(0.132-6.047),respectively.AP(95% CI)were 0.663(0.493-0.834),0.623(0.451-0.796),0.614(0.467-0.762),0.503(0.237-0.769),respectively.SI(95% CI)were 3.919(2.033-7.558),4.061(1.959-8.420),3.433(2.013-5.853),2.506(1.250-5.024),respectively;LP(a)had no additive interaction with smoking and obesity,RERI(95% CI)were 1.141(-0.640-2.922),2.674(-0.889-6.237),respectively.AP(95% CI)were 0.202(-0.077-0.482),0.451(0.094-0.808),respectively.SI(95% CI)CI)were 1.327(0.852-2.064)and 2.185(0.958-4.987),respectively.Conclusion:1.In AMI population,the level of LP(a)was skewed,and the proportion of LP(a)increase was higher than that of the general population.2.LDL-C,non-HDL-C,LP(a),hypertension,diabetes,smoking,obesity,and age are independent risk factors for the degree of coronary artery stenosis.3.When high LP(a)combined with high LDL-C,high non-HDL-C,diabetes,hypertension,smoking,obesity,the risk of severe coronary artery lesions is greater than that of risk factors alone.LP(a)had positive additive interactions with LDL-C,non-HDL-C,hypertension and diabetes mellitus on coronary artery lesions,but no additive interactions with smoking and obesity.Therefore,we speculate that LP(a)is a complementary relationship with LDL-C,non-HDL-C,hypertension,and diabetes in the process of coronary artery disease,while the increased risk of LP(a)and smoking and obesity may simply be due to the superposition of risk factors.