A Clinical Study Of Novel Lipid Metabolism Markers And Cardiac Fatty Acid-binding Protein And The Risk Of Coronary Heart Disease

Background:Low density lipoprotein-cholesterol(LDL-C)plays an important role in the prevalence of coronary artery disease(CAD).Due to the heterogeneity of LDL particles,these subgroups may make different contributions to the development of CAD.Hence,there are more and more studies focusing on the correlations between LDL particles and CAD have been conducted in recent years.Small dense low-density lipoprotein-cholesterol(sdLDL-C),a novel atherogenic lipoprotein of LDL particles,has been reported to be closely related to the occurrence and development of CAD in previous studies.However,up to now,the prognostic value of sdLDL-C in CAD patients combined with hypertension has not been well-determined.Given this background,we aimed to investigate the associations between sdLDL-C with disease severity,hypertensive status and clinical outcome in patients with CAD.Methods:From January 2012 through February 2017,a total of 4,594 consecutively stable patients with angiography-proven CAD were enrolled and followed up for a median of 51 months.The baseline characters and laboratory data were collected from each patient.Serum sdLDL-C levels were measured by direct quantitative measurement using automated chemistry analyzers.The baseline characteristics were analyzed and compared according to the tertiles of sdLDL-C levels.Patients were divided into hypertensive group and non-hypertensive group according to their blood pressure(BP)status,and hypertensive group was further divided into well-controlled group and poorly-controlled group.The severity of CAD was evaluated by the number of stenotic vessels,Gensini score,and Syntax score.Logistic regression model was used to evaluate the relationship between serum sdLDL-C levels and the severity of coronary artery stenosis.The cardiovascular events(CVEs)defined with all-cause death(death mainly caused by cardiovascular diseases),non-fatal myocardial infarction,stroke,coronary revascularization(percutaneous coronary intervention and/or coronary artery bypass grafting),and angina-related hospitalization.Cox regression analyses were used to evaluate the associations of sdLDL-C and CVEs in this population.The event-free survival rate was estimated by and compared with log-rank test in Kaplan-Meier curves.Results:Date showed that patients with hypertension had higher sdLDL-C levels than patients without hypertension(30.68± 17.41 mg/dL vs 29.39± 15.55 mg/dL,P=0.010).The hypertensive patients in the upper tertile of sdLDL-C group had significantly higher Gensini score,higher Syntax score and more patients with multivessel disease than those with lower sdLDL-C levels(P<0.05,respectively).During a median of 51 months follow-up,363 CVEs occurred in hypertensive patients,but there was no significant association of sdLDL-C with CVEs in total hypertensive patients(P>0.05).Interestingly,according to the status of BP,the hypertensive patients were further divided into well-controlled group(n=1695)and poorly-controlled group(n=1310).Hypertensive patients with poorly-controlled BP had higher sdLDL-C levels than patients with well-controlled BP(P<0.05).Additionally,149 CVEs occurred inpatients with poorly-controlled BP.The univariate and multivariate Cox regression analyses indicated serum sdLDL-C levels were independently associated with CVEs after adjusting for the variables such as age,gender,body mass index,current smoking,family history of CAD,hyperlipidemia,diabetes and lipids-lowering treatment[unadjusted hazard ratio(HR):1.631,95%confidence interval(CI):1.092-2.436,P=0.017;adjusted HR:1.673,95%CI:1.105-2.535,P=0.015].Nevertheless,sdLDL-C could not predict for CVEs in hypertensive patients with well-controlled BP(P>0.05).Kaplan-Meier analysis also showed the risk of CVEs was increased among hypertensive patients with poorly controlled hypertension in the higher tertile of sdLDL-C group compared to ones in the lower group(P=0.016).Conclusions:Data from the present study firstly provided the novel information that elevated levels of sdLDL-C were independently associated with worse outcomes in hypertensive patients with CAD according to hypertensive status,suggesting that measurement of sdLDL-C in these patients might help to clinical risk stratification.Background:Lipoprotein(a)[Lp(a)]is an important lipid index involved in the process of atherosclerotic cardiovascular disease.In recent years,a large number of studies have confirmed the promoting role of Lp(a)in the development of coronary artery disease(CAD).Besides,type 2 diabetes mellitus(T2DM)is also an important risk factor for CAD,which is often accompanied by dyslipidemia,including the elevation of Lp(a)levels.However,the role of Lp(a)in the development of CAD in patients with T2DM has not been fully determined.Therefore,the purpose of this study was to investigate the correlations between Lp(a)level with the severity of coronary disease in patients with T2DM.Methods:A total of 2,040 patients with T2DM who underwent selective coronary angiography(coronary angiography,CAG)were included in the present study.The medical history and laboratory test data of each patient were collected,and the fasting plasma Lp(a)levels were determined.The patients were divided into four subgroups according to the quartiles of Lp(a)levels(Quartile 1:0-6.25 mg/dL;Quartile 1:6.26-14.55 mg/dL;Quartile 3:14.56-33.44;Quartile 4:>33.44 mg/dL).According to result of CAG,the patients were divided into CAD group and non-CAD group.The severity of CAD was assessed by Gensini score,the number of stenosis coronary arteries,and the history of myocardial infarction.Subgroups analyses were conducted according to the severity of CAD.Univariate and multivariate regression analyses were used to evaluate the relationship between Lp(a)level with the severity of CAD in patients with T2DM.Results:We found that Lp(a)levels were higher in T2DM patients with CAD than those in non-CAD group(15.00 mg/dL vs 11.88 mg/dL,P=0.025).According to the severity of CAD,the patients were divided into subgroups for further analysis.The results showed that Lp(a)levels were higher in T2DM patients with myocardial infarction,multi-vessel disease(3 or more),and high Gensini score than those in the controlled groups(myocardial infarction vs no myocardial infarction:15.66 mg/dL vs 14.18 mg/dL,P=0.026;multi-vessel vs single-vessel:16.43 mg/dL vs 11.84 mg/dL,P=0.002;high Gensini score vs low Gensini score:17.10 mg/dL vs 13.31 mg/dL,P=0.015).Meanwhile,we divided patients into four subgroups based on the quartiles of Lp(a)levels,the univariate regression analysis showed that increased Lp(a)levels were positively correlated with the severity of CAD[myocardial infarction:odds ratio(OR)=1.414,95%confidence interval(CI)=1.048-1.908,P=0.023;high Gensini score:OR=1.369,95%CI=1.044-1.796,P=0.023;multi-vessel lesions:OR=1.398,95%CI=1.069-1.828;P=0.014];In multivariate regression analysis after adjusted for multiple risk factors such as age,sex,hypertension,hyperlipidemia lipids,and lipid-lowering treatment,increased Lp(a)levels were still associated with the severity of CAD(myocardial infarction:OR=1.523,95%CI=1.108-2.092,P=0.010;high Gensini score:OR=1.388,95%CI=1.049-1.837,P=0.022;multi-vessel lesions:OR=1.455,95%CI=1.102-1.921;P=0.008).Conclusions:Lp(a)levels were elevated in patients with T2DM and CAD,and were also positively correlated with the severity of coronary artery stenosis.These data suggested that clinical attention should be paid to the elevation of Lp(a)in diabetic patients,which could help to the assessment of the coronary lesions in such patients.Background:Heart-type fatty acid binding protein(H-FABP),a novel cardiac marker for myocardial injury,plays an important role in early diagnosis of acute myocardial injury.Moreover,H-FABP has been reported to be a prognostic marker for future cardiovascular risk in acute coronary syndrome.However,the prognostic utility of H-FABP in patients with stable coronary artery disease(CAD)has not been well investigated.Hence,the objective of this study was to determine the associations between H-FABP with the severity of coronary disease,and cardiovascular events(CVEs)in patients with stable CAD.Methods:In this study,a total of 4,370 stable patients with angiography-proven CAD were consecutively enrolled and followed up.The medical history and blood samples were collected from each patient.The baseline H-FABP level was detected.The study included two parts:first,the severity of CAD was assessed by Gensini Score(GS)and the numbers of diseased vessels,and the correlation between H-FABP to the severity of coronary artery was evaluated.Then,the Cox regression analysis with hazard ratio(HR)and 95%confidence interval(95%CI),and Kaplan-Meier analysis were used to evaluate the relation of H-FABP to CVEs.The CVEs were defined as cardiovascular death,non-fatal myocardial infarction,ischemic stroke and coronary revascularization(percutaneous coronary intervention and/or coronary artery bypass graft).Results:During a median follow-up of 51 months,353 CVEs(8.1%)occurred.H-FABP levels were significantly higher in patients with events compared to those without(2.83±2.27ng/mL vs 2.38±1.72ng/mL,P<0.001).Patients were divided into four subgroups according to the quartiles of H-FABP as quartile 1(<1.50 ng/mL),quartile 2(1.50-2.20 ng/mL),quartile 3(2.21-3.00 ng/mL),quartile 4(>3.0 ng/mL).Firstly,patients in the highest levels of H-FABP group had increased rate of multi-vessel coronary stenosis(43.1%vs 36.2%,P=0.012),and higher GS compared with those in the lowest group(37.9±35.7 vs 31.9±30.3,P<0.001).In addition,the incidence of CVEts increased with the increase of H-FABP level(5.8%vs 7.4%vs 8.3%vs 11.3%,P<0.001).Then,in Cox regression analysis,the highest quartile of H-FABP levels were found to be associated with increased risk of CVEs[unadjusted HR:1.767;95%CIs:1.301-2.400,P<0.001].After adjusted for the valuables including age,gender,hypertension,dyslipidemia,current smoking,diabetes,HbAlc,and family history of CAD,patients in the upper levels of H-FABP remained to be independently correlated with worse cardiovascular outcomes[adjusted HR:1.453;95%confidence intervals(CIs):1.040-2.029,P=0.028],significantly in cardiovascular death(unadjusted HR:4.427;95%CIs:2.139-9.164,P<0.001;adjusted HR:2.865;95%CIs:1.315-6.243,P=0.008).Conclusions:Our results firstly indicated that H-FABP was associated with the severity of coronary artery stenosis and was also a useful predictor for CVEs in patients with stable CAD,suggesting that measurement of H-FABP in patients with stable CAD may be helpful in risk assessment.Background:Previous studies have reported that heart-type fatty acid binding protein(H-FABP),as a novel marker of myocardial injury,can help to diagnose myocardial injury and predict the risk of coronary artery disease(CAD).And some studies have also shown that levels of H-FABP elevated in patients with diabetes mellites(DM),hypertension and heart failure.Usually,the cardiovascular risks increase in CAD patients combined with diabetes.However,the predictive value of H-FABP for the prognosis of patients with CAD and impaired glucose metabolism(IGM)remains unclear.Therefore,the purpose of this study was to investigate the prognostic value of H-FABP in CAD patients with IGM.Methods:A total of 4,594 patients with stable CAD underwent coronary angiography were included in this study.The medical history and fasting blood samples were collected from each patient.Patients were divided into three subgroups(normal glucose regulation:NGR group;pre-DM group;DM group)according to their glucose metabolism status.Plasma H-FABP levels at baseline were measured by latex immunoturbidimetric method,and subgroup analysis was performed based on the tertiles of H-FABP.All patients were followed up for cardiovascular end points,defined as cardiovascular death,non-fatal myocardial infarction,stroke,and coronary revascularization(including percutaneous coronary intervention and/or coronary artery bypass grafting).The Cox regression analysis(hazard ratio:HR;95%confidence interval:95%CI)and Kaplan-Meier survival analysis curves were used to assess the associations of H-FABP with glucose metabolism status and cardiovascular events.Results:During an average follow-up period of 51 months,380 cardiovascular events occurred.The levels of H-FABP in the event group was higher than those in the non-event group(2.95±2.52ng/mL vs 2.41±1.79g/mL,P<0.001).Patients were divided into normal blood glucose group(NGR)and IGM groups(including pre-DM group and DM group)for subgroup analyses.We found that the H-FABP elevated in the IGM groups(NGR group vs pre-DM group vs DM group:2.10±1.13g/mL vs 2.41±1.71g/mL vs 2.64±2.21g/mL,P<0.001).Patients with IGM were then stratified into subgroups according to H-FABP tertiles,we found that in both pre-DM and DM group,increased levels of H-FABP were positively correlated with cardiovascular events(pre-DM group:HR:1.335,95%CI:1.059-1.772,P=0.039;DM group:HR:1.322,95%CI:1.035-1.730,P=0.040;all HRs adjusted for risk factors included age,sex,hypertension,hyperlipidemia,body mass index,smoking history,and family history of CAD).When combined glucose metabolism status with H-FABP stratification to further investigate the relationship between IGM,H-FABP,and cardiovascular events.The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs(P<0.001).Moreover,data from Cox regression analysis indicated that patients in the pre-DM group with tertile 3 levels of H-FABP had an increased risk of cardiovascular events(adjusted HR:1.855,95%CI:1.076-3.214,P=0.033)compared with baseline reference group(NGR with tertile 1 H-FABP).In the DM group,the risk of cardiovascular events increased when h-FABP levels increased(tertile 1:adjusted HR:2.131,95%CI:1.157-3.925,P=0.015;tertile 2:adjusted HR:2.171,95%CI:1.179-3.997,P=0.013;tertile 3:adjusted HR:2.560,95%CI:1.409-4.650,P=0.002).Conclusions:Our data,for the first time,showed that elevated H-FABP levels were associated with worse clinical outcomes in CAD patients with both pre-DM and DM.These findings provided new information on the utility of H-FABP as a potential prognostic marker in patients with CAD and IGM.