Abstract
Background Cardiovascular disease(CVD)is the most common chronic non-communicable disease,with an increasing prevalence worldwide and is also the leading cause of death globally.The ratio of high-sensitivity C-reactive protein(hs-CRP)to albumin(ALB),known as the C-reactive protein to albumin ratio(CAR),is a novel inflammatory marker.Our research team has previously investigated its association with CVD and found that a high CAR is closely related to an increased risk of CVD onset.Existing studies have reported that the risk of CVD associated with high levels of hs-CRP decreases gradually from middle-aged populations(51-64 years)to elderly populations(≥65 years).However,it remains unclear whether the impact of CAR,as a novel marker for assessing CVD risk,on incident CVD differs among different age groups.Objective To explore the impact of CAR on incident CVD in different age groups.Methods A total of 54 951 participants who attended the third health examination in the Kailuan Cohort Study in 2010 were included.Demographic and clinical data,physical examination results,and laboratory test indicators of the participants were collected.The CAR was calculated and log-transformed(lgCAR).Participants were divided into four quartile groups based on lgCAR:Q1(lgCAR<-4.34,n=13 744),Q2(-4.34≤lgCAR<-3.67,n=13 731),Q3(-3.67≤lgCAR<-2.83,n=13 736),and Q4(lgCAR≥-2.83,n=13 740).They were also stratified by age into<40 years(n=9 617),40-49 years(n=12 633),50-59 years(n=17 740),and≥60 years(n=14 691).Follow-up began from the time of the 2010 health examination and ended at the occurrence of CVD,all-cause death,or the end of follow-up on 2021-12-31.The cumulative incidence of CVD in the total population and each age group was calculated using the Kaplan-Meier method,and comparisons between groups were made using the Log-rank test.Cox proportional hazards regression analysis was used to assess the risk of CVD in the total population at different CAR levels.The multiplicative interaction between age and CAR quartile groups was explored using the Cox regression model,and the analysis was repeated after stratifying by age.To eliminate the impact of medication use on the results,sensitivity analyses were conducted by excluding participants who took antihypertensive,antidiabetic,or lipid-lowering drugs at baseline or during follow-up.To eliminate the impact of reverse causality and short follow-up duration,sensitivity analyses were conducted by excluding participants with a follow-up duration of less than 1 year.Given the high mortality risk of CVD and the potential competition between CVD and patient death,a competing risk model for death was used to analyze the impact of different CAR levels on CVD in participants aged 60 years and older.Results A total of 54 951 participants were included in the final analysis,including 41 083 men(74.8%)and 13 868 women(25.2%),with a mean age of 51.7±12.8 years.The mean lgCAR values in groups Q1 to Q4 were-5.6±1.5,-4.0±0.2,-3.3±0.2,and-2.2±0.6,respectively.There were statistically significant differences among the Q1 to Q4 groups in terms of age,gender,higher education,smoking,alcohol consumption,physical exercise,BMI,hs-CRP,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,total cholesterol,systolic blood pressure,diastolic blood pressure,diabetes,hypertension,antihypertensive medication use,antidiabetic medication use,lipid-lowering medication use,estimated glomerular filtration rate,alanine aminotransferase,ALB,and lgCAR(P<0.05).The mean follow-up duration was 10.38±1.99 years,during which 3,444 participants(6.27%)developed CVD.The number of incident CVD cases in groups Q1 to Q4 was 659,809,901,and 1 075,respectively,with cumulative incidences of 4.79%,5.89%,6.56%,and 7.82%.The Log-rank test showed that the differences in cumulative incidence of CVD among the Q1 to Q4 groups in the total population and different age groups were statistically significant(P<0.05).The results of The Cox proportional hazards regression model indicated that after adjusting for confounding factors,the risk of incident CVD in group Q4 was 1.20 times that of group Q1(HR=1.20,95%CI=1.07-1.35),and there was an interaction between age and CAR group with CVD(Pinteraction=0.021).In the<40 years,40-49 years,50-59 years,and≥60 years age groups,the risk of incident CVD in group Q4 was 1.13 times(HR=1.13,95%CI=0.55-2.33),1.44 times(HR=1.44,95%CI=1.06-1.96),1.24 times(HR=1.24,95%CI=1.02-1.50),and 1.11 times(HR=1.11,95%CI=0.93-1.33)that of group Q1,respectively.The results of the sensitivity analysis showed that after excluding participants who took lipid-lowering drugs at baseline or during follow-up,there was an interaction between age and CAR group with CVD(Pinteraction=0.020).After excluding participants who took antidiabetic drugs at baseline or during follow-up,there was an interaction between age and CAR group with CVD(Pinteraction=0.015).After excluding participants with a follow-up duration of less than 1 year,there was an interaction between age and CAR group with CVD(Pinteraction=0.045).The Cox proportional hazards regression model analysis found that the association between CAR group and incident CVD was consistent with the main results,and the association between CAR group and incident CVD still existed in the middle-aged population(40-59 years),with the risk of CVD associated with elevated CAR decreasing with age.After excluding participants who took antihypertensive drugs at baseline or during follow-up,the interaction between age and CAR group with CVD was not significant(Pinteraction=0.114).The Cox proportional hazards regression model analysis found that compared with the main results,in the 50-59 years age group,the statistical association between CAR group and incident CVD was not significant(P>0.05).The competing risk model for death was used to analyze the impact of different CAR levels on CVD in participants aged 60 years and older,and the results were consistent with the main results,showing no association between CAR and incident cardiovascular events.Conclusion A high CAR level is an independent risk factor for incident CVD.The association between CAR and the risk of CVD onset is age-dependent in the middle-aged population,and the risk of CVD associated with elevated CAR decreases with increasing age.关键词
心血管疾病/超敏C反应蛋白/白蛋白/队列研究/开滦队列Key words
Cardiovascular disease/High-sensitivity C-reactive protein/Albumin/Cohort study/Kailuan Cohort分类
医药卫生
