Lipoprotein(a) as a Marker for Predicting the Presence and Severity of Coronary Artery Disease in Untreated Chinese Patients Undergoing Coronary Angiography

Objective Low-density lipoprotein cholesterol（LDL-C） has been well known as the risk factor of coronary artery disease（CAD）. However, the role of lipoprotein（a） [Lp（a）] in the development of CAD is of great interest but still controversial. Thus, we aim to explore the effect of Lp（a） on predicting the presence and severity of CAD in Chinese untreated patients, especially in combination with LDL-C. Methods We consecutively recruited 1,980 non-treated patients undergoing coronary angiography, among which 1,162 patients were diagnosed with CAD. Gensini score（GS） was used to assess the severity of CAD. Lp（a） was measured by immunoturbidimetric method. Results Patients with CAD had higher level of LDL-C and Lp（a） compared with non-CAD（P 〈 0.05）. Multivariable logistic regression revealed that Lp（a） 〉 205 mg/L（highest tertile） predicted 1.437-fold risk for CAD（95% CI： 1.108-1.865, P = 0.006） and 1.480-fold risk for high GS（95% CI： 1.090-2.009, P = 0.012） respectively. Interestingly, concomitant elevated level of Lp（a） and LDL-C conferred the highest risk for both presence [OR = 1.845, 95% CI： 1.339-2.541, P 〈 0.001] and severity [OR = 1.736, 95% CI： 1.188-2.538, P = 0.004] of CAD. Conclusion Lipoprotein（a） is a useful marker for predicting the presence and severity of CAD, especially combined with LDL-C.

MODIFIED CLASSIC RISK FACTORS FOR CORONARY ARTERY DISEASE IN CHINESE HAN POPULATION

Objective To investigate the levels of cardiovascular disease risk factors and their relations to clinical phenotype associated with coronary artery disease(CAD).Methods The subjects were recruited from five independent cardiovascular centers.Coronary angiography was employed to define the CAD with stenosis in each major vessel ≥70% and control with stenosis <10% in every lesion.The classic risk factors including family history,body mass index,smoking habits,hypertension,diabetes mellitus,and serum lipid levels were surveyed according to established criteria.Associations between risk levels and clinical phenotypes were assessed by case control and correlation analysis.Results A total of 762 individuals were collected,including 481 men and 281 women,aged from 17 to 81(mean 60±10) years.The patients with CAD accounted for 55.5% of all participants,and controls 44.5%,respectively.Compared with the pattern in published data,our study showed that mean serum high density lipoprotein cholesterol(HDL-C) level was significantly lower(P<0.001) and triglycerides was significantly higher(P<0.001),while total cholesterol(TC) and low density lipoprotein cholesterol levels were comparative(both P>0.05).The prevalence of low HDL-C(<40 g/L) and hypertriglyceridemia(>150 g/L) were 27.2% and 41.4%,respectively.Mean serum levels of HDL-C and apolipoprotein A1 were significantly higher in female subjects than in male(P<0.001).Lower HDL-C functioned as an independent risk factor for CAD only in men(RR=2.8,95%CI:1.5-4.2,P<0.001),yet increased non-HDL cholesterol combined with diabetes mellitus and obesity seemed to play a key role in the development ofCAD in women.Similarity in risk association with CAD was found for hypertension and TC/HDL ratio in male and female subjects,while family history had no relationship with the presence of CAD.Conclusion It is remarkable that emphasis of intervention in future should be given on the prevalent low serum HDL-C and its strong risk correlation with the presence of CAD in male subjects of Chinese Han population.

Expert Survey on the Prevention and Treatment Situation of Traditional Chinese Medicine for Coronary Artery Disease

Objective: To grasp the current situation of Traditional Chinese Medicine (TCM) on prevention and treatment for coronary artery disease (CAD) and the possible advantages and disadvantages. Method: Using a survey in the form of questionnaire among 60 cardiovascular disease experts, to grasp current situation of TCM on prevention and treatment of CAD and the possible advantages and disadvantages. Results: In most areas of China, CAD is common, and angina is the most common clinical type. More than 91% experts choose to integrate traditional and western medicine for treatment and prevention of CAD. TCM proprietary medicine, traditional herbal decoction and intravenous TCM are widely used in the clinical work. Clinical advantages of TCM in the prevention of CAD that are listed in the questionnaire include improving symptoms, enhancing quality of life, increasing exercise tolerance, improving cardiac function, relieving angina, secondary prevention of myocardial infarction, etc. The shortcomings include troublesome brewing of herbal medicine, unpleasant taste of decoction, minimal clinical evidence, slow onset of effects and non-standardized prescription of medicine, etc. Conclusion: The survey reflects the present situation of clinical diagnosis and treatment of TCM on prevention and treatment of CAD to a certain extent;more accurate conclusions need the broader, deeper and large-scale clinical survey.

Association of single nucleotide polymorphism rs2076185 in chromosome 6P24.1 with premature coronary artery diseases in Chinese Han population

Objectives To study the association of single nucleotide polymorphism （SNP） rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases （PCAD） in Chinese Hun population. Methods A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography （CAG） results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. Results The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium （P 〉 0.05）. The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant （P = 0.042）. The genotype distribution ofrs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model （OR： 0.828, 95% CI： 0.711-0.964, P = 0.014）, and in the dominant model （OR： 0.753, 95% CI： 0.591-0.958, P = 0.021）. After removing the confound- ing variables, the rs2076185 polymorphisms was associated with PCAD in the additive model （OR： 0.775, 95% CI： 0.648-0.928, P = 0.005）, in the dominant model （OR： 0.698, 95% CI： 0.527-0.925, P = 0.012）, and in the recessive model （OR： 0.804, 95% CI： 0.538-0.983, P - 0.038）. Conclusion Allele G of rs2076185 reduces the PCAD risks in Chinese Hun population, therefore it could be a coronary artery diseases protective factor in Chinese Hun population.

Genetic variants of the class A scavenger receptor gene are associated with coronary artery disease in Chinese

The class A scavenger receptor, encoded by the macrophage scavenger receptor 1 （MSR1） gene, is a pattern recognition receptor （PPR） primarily expressed in macrophages. It has been reported that genetic polymorphisms of MSR1 are significantly associated with the number of diseased vessels and coronary artery narrowing greater than 20% in Caucasians. However, whether it links genetically to coronary artery disease （CAD） in Chinese is not defined. Here, we performed an independent case-control study in a Chinese population consisting of 402 CAD cases and 400 controls by genotyping ten single nucleotide polymorphisms （SNPs） of MSR1. We found that rs416748 and rs13306541 were significantly associated with an increased risk of CAD with per allele odds ratio （OR） of 1.56 [95% confidence interval （CI） = 1.28-1.90; P 〈 0.001] and 1.70 （95% CI = 1.27-2.27; P 〈 0.001）, re- spectively. Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of CAD / in combination with traditional risk factors of CAD in Chinese population.

Relationship of lipid and lipoprotein ratios with coronary severity in patients with new on-set coronary artery disease complicated with type 2 diabetics

Background Diabetes mellitus （DM） is associated with coronary artery disease （CAD） progression. Although previous studies have demonstrated the association of lipid and lipoprotein ratios with CAD, no data are currently available concerning the relationship between lipid and lipoprotein ratios and the severity of new on-set CAD in diabetics. Therefore, the aim of the present study was to investigate the usefulness of lipid and lipoprotein ratios in predicting the severity of CAD in patients with type 2 DM （T2DM）. Methods A total of 380 consecutive T2DM patients with new on-set CAD were enrolled in the present study. Then, they were classified into the three groups ac-cording to Gensini score （GS） tertiles. The relationship between lipid and lipoprotein ratios currently used and the GS was investigated. Results Positive correlations of natural log-transformed GS （lnGS） with apolipoprotein B to apoA-I ratio （apoB/apoA-I）, non-high-density lipoprotein cholesterol to apoA-I ratio （non-HDL-C/apoA-I）, and low-density lipoprotein cholesterol to apoA-I ratio （LDL-C/apoA-I） were found （r = 0.18, 0.13, 0.12, respectively, all P 〈 0.05）. Multivariate logistic analysis indicated apoB/apoA-I as the strongest predictor for high GS （OR = 5.67, 95% CI： 1.45-23.92, P = 0.003）. Area under receivers operating characteristic curve of apoB/apoA-I was 0.63 （95% CI： 0.60-0.66, P = 0.001） for predicting high GS. The optimal cutoff value of apoB/apoA-I to predict high GS was 0.72 with the sensitivity of 61.2% and the specificity of 62.1%. Conclusions Lipid and lipoprotein ratios might be useful for predicting the severity of new on-set CAD in T2DM patients, and the apoB/apoA-I appeared as the most significant predictor in this population.

Correlation between betatrophin/angiogenin-likeprotein3/lipoprotein lipase pathway and severity of coronary artery disease in Kazakh patients with coronary heart disease

BACKGROUND The results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels.However,there are still differences studies on the correlation and interaction mechanism between betatrophin,angiogenin-likeprotein3(ANGPTL3)and lipoprotein lipase(LPL).In our previous studies,we found an increase in serum ANGPTL3 Levels in Chinese patients with coronary heart disease(CHD).Therefore,we retrospectively studied Kazakh CHD patients.AIM To explore the correlation between the betatrophin/ANGPTL3/LPL pathway and severity of coronary artery disease(CAD)in patients with CHD.METHODS Nondiabetic patients diagnosed with CHD were selected as the case group;79 were of Kazakh descent and 72 were of Han descent.The control groups comprised of 61 Kazakh and 65 Han individuals.The serum levels of betatrophin and LPL were detected by enzyme-linked immunosorbent assay(ELISA),and the double antibody sandwich ELISA was used to detect serum level of ANGPTL3.The levels of triglycerides,total cholesterol,and fasting blood glucose in each group were determined by an automatic biochemical analyzer.At the same time,the clinical baseline data of patients in each group were included.RESULTS Betatrophin,ANGPTL3 and LPL levels of Kazakh patients were significantly higher than those of Han patients(P=0.031,0.038,0.021 respectively).There was a positive correlation between the Gensini score and total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),betatrophin,and LPL in Kazakh patients(r=0.204,0.453,0.352,0.471,and 0.382 respectively),(P=0.043,0.009,0.048,0.001,and P<0.001 respectively).A positive correlation was found between the Gensini score and body mass index(BMI),TC,TG,LDL-C,LPL,betatrophin in Han patients(r=0.438,0.195,0.296,0.357,0.328,and 0.446 respectively),(P=0.044,0.026,0.003,0.20,0.004,and P<0.001).TG and betatrophin were the risk factors of coronary artery disease in Kazakh patients,while BMI and betatrophin were the risk factors in Han patients.CONCLUSION There was a correlation between the betatrophin/ANGPTL3/LPL pathway and severity of CAD in patients with CHD.

Lipoprotein(a)variability is associated with mean follow-up Creactive protein in patients with coronary artery disease following percutaneous coronary intervention

BACKGROUND Increased lipoprotein(a)[lp(a)]has proinflammatory effects,which increase the risk of coronary artery disease.However,the association between lp(a)variability and follow-up C-reactive protein(CRP)level in patients undergoing percutaneous coronary intervention(PCI)has not been investigated.AIM To explore the association between lp(a)variability and mean CRP levels within the 1st year post-PCI.METHODS Results of lp(a)and CRP measurements from at least three follow-up visits of patients who had received PCI were retrospectively analyzed.Standard deviation(SD),coefficient of variation(CV),and variability independent of the mean(VIM)are presented for the variability for lp(a)and linear regression analysis was conducted to correlate lp(a)variability and mean follow-up CRP level.The relationship of lp(a)variability and inflammation status was analyzed by restricted cubic spline analysis.Finally,exploratory analysis was performed to test the consistency of results in different populations.RESULTS A total of 2712 patients were enrolled.Patients with higher variability of lp(a)had a higher level of mean follow-up CRP(P<0.001).lp(a)variability was positively correlated with the mean follow-up CRP(SD:β=0.023,P<0.001;CV:β=0.929,P<0.001;VIM:β=1.648,P<0.001)by multivariable linear regression analysis.Exploratory analysis showed that the positive association remained consistent in most subpopulations.CONCLUSION Lp(a)variability correlated with mean follow-up CRP level and high variability could be considered an independent risk factor for increased post-PCI CRP level.

Association between LDL, Apolipoprotein-B Apolipoprotein A-I and Lipoprotein(a) and Severity of Coronary Artery Disease Based on Coronary Angiography

Atherosclerosis is the most important contributor to increasing burden of coronary artery disease (CAD). Growing evidence suggests that the ratios of Apo B/Apo A-I and Lp(a) are better indexes for risk assessment of CAD. Elevated plasma levels of lipoprotein(a) in humans represent a major in-herited risk factor for atherosclerosis. Thus, a study was performed to determine the association betwwen serum Apo B, Apo A-I, and lipoprotein(a) levels, and severity of CAD in patients with CAD confirmed on coronary angiography findings. An analytical case control study was carried out with 85 patients (58 males and 27 females) 40 - 60 years of age confirmed as having CAD on coronary angiography and 85 age and sex matched healthy volunteers as controls. Serum samples were an-alyzed for Apo A-1 LDL, Apo B, Apo A-I, and lipoprotein(a) concentration and the severity of CAD was assessed using coronary angiography scoring method. Patients with CAD had significantly high serum LDL-C, Apo B and Lp(a) levels compared to control subjects. However, serum Apo A-I level did not show a significant difference between two groups. Subjects with a positive family history of CAD with increased serum Lp(a) ≥ 17.3 mg/dL have high risk for development of CAD. Present study suggests that serum Lp(a) cut-off value of 17.3 mg/dL may be an important predictor in ruling out major vessel disease and luminal narrowing by atheroma.

Impact of estimated HDL particle size via the ratio of HDL-C and apoprotein A-I on short-term prognosis of diabetic patients with stable coronary artery disease

BackgroundRevascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein （HDL） particle size （eHDL-S）, the ratio of HDL cholesterol （HDL-C） to apoprotein A-I （apoA-I）, is associated with the clinical outcomes of diabetic patients with stablecoronary artery disease （CAD）.MethodsWe per-formed a prospective cohort study of 328 patients diagnosed with stable CAD by coronary angiography. Patients were followed up for a mean duration of 12 months. The patients were divided into three groups by the tertiles of eHDL-S： low eHDL-S （〈 0.71,n= 118）; interme-diate eHDL-S （0.71-0.79,n= 111）; and high eHDL-S （〉 0.79,n= 99）. The associations between the baseline eHDL-S and short-term out-comes were evaluated using the Kaplan-Meier method and Cox proportional regression.Results The low eHDL-S group had higher trig-lyceride, hemoglobin A1c, uric acid, and leukocyte count than the other groups. During the follow-up period, 47/328 patients experienced a pre-specified outcome. According to the Kaplan-Meier analysis, the incidence of pre-specified outcomes was lower in the high eHDL-S group （P = 0.04）. However, eHDL-S was not independently associated with adverse outcomes in Cox proportional hazards regression （haz-ard ratio （HR）： 0.23, 95% confidence interval （95% CI）： 0.01-11.24,P = 0.493）.ConclusionAlthough the eHDL-S was associated with inflammatory biomarkers, it was not independently associated with the short-term prognosis of diabetic patients with stable CAD in the era of revascularization and potent statin therapy.

Study on therapeutic targets networks of xuefu-zhuyu decoction and gualou-xiebai-banxia decoction for the treatment of coronary artery disease

Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.

A New Perspective for Chinese Medicine Intervention for Coronary Artery Disease: Targeting Inflammation

Inflammation, which plays a critical role in atherosclerosis and the occurrence of acute cardiovascular events, may be a new target for treatment of coronary artery disease(CAD) to reduce residual cardiovascular risk. Recently, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease(CANTOS), the largest scale clinical trial that targeted inflammation but not lipids, has affirmed for the first time the inflammatory hypothesis of artherosclerosis and marked the advent of an exciting era of targeting inflammation for the prevention and treatment of cardiovascular diseases. Chinese medicine(CM) is a promising adjuvant therapy for CAD in light of its safety and pleiotropic effect of anti-inflammation, anti-platelet, lipid-regulating, endothelium-protection, microcirculation-improving, etc. In recent years, exploration of anti-inflammatory treatment of CAD with CM has been going on from theory to practice. Taking CANTOS as an example, the design strategy to combine CM and Western medicine to inhibit inflammation were discussed in this paper, which might provide a new perspective for CM intervention on CAD.

Association of common polymorphisms in the LRP6 gene with sporadic coronary artery disease in a Chinese population

Background Genetic factors contribute to the development of coronary artery disease （CAD）.Recently,a missense mutation in the low density lipoprotein receptor related protein 6 （LRP6） gene,encoding low density lipoprotein receptor related protein 6,has been implicated in an autosomal dominant form of early-onset CAD.The aim of this study was to determine whether the common variants in LRP6 are associated with sporadic CAD in Chinese.Methods A total of 766 CAD patients and 806 healthy controls were included in this study.The presence of angiographic CAD was determined by coronary angiographic analysis.Six signal nucleotide polymorphisms （SNPs） were genotyped using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique.Results A significant association was detected between rs11054731 in LRP6 intron 2 and CAD in our cohort （P=0.001）.The CC genotype and C allele frequency in the case group were 52% and 72%.Using a dominant model of inheritance,the C allele of rs11054731 was shown to be an independent risk factor for CAD with an OR of 1.45 （95% CI：1.19-1.77,P=0.0002）.With the stratification according to the number of affected coronary arteries,an association was observed between rs11054731 and CAD （P=0.0002）.No significant association was observed between any other SNPs and the risk of CAD.Conclusion The C allele of the rs11054731 within the LRP6 gene was associated with increased risk and extent of CAD in Chinese.

Genetic variability in adapter proteins with APPL1/2 is associated with the risk of coronary artery disease in type 2 diabetes mellitus in Chinese Han population

Background Adaptor proteins containing PH domain, PTB domain, and leucine zipper motif 1 and 2 （APPL1/2） play a key role in cell proliferation in many tissues. APPL1 or APPL2 as an adaptor for adiponectin receptors mediates the signaling pathway of adiponectin which acts as an anti-atherosclerotic adipokine. This study aimed to investigate whether genetic variations in the APPL 1/2 genes affect the risk of coronary artery disease （CAD） in Chinese patients with type 2 diabetes mellitus （T2DM）. Methods Seven haplotype-tagging single nucleotide polymorphisms （tag-SNPs） were selected from CHB HapMap database （Phase II） and total 203 CAD-positive cases and 106 CAD-negative controls with T2DM were genotyped for the 7 tag-SNPs by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. Results The minor allele G of rs4640525 at APPL1 locus was protective from CAD in patients with T2DM, with the carriers of genotype CC at higher risk of CAD compared with non-carriers （OR=2.830, 95% Cl 1.285-6.230, P=0.010; OR＇=4.992, 95% C1=1.758-14.173, P＇0.003, after adjustment for the other known CAD risk factors）; the homozygotes of AA at rs11112412 in APPL2 gene had higher risk of CAD compared with those of GG （adjusted OFt=5.697, 95% Cl 1.006-32.257, P=0.049）. Conclusion Genetic variation（s） in APPL 1/2 may be associated with CAD risk in T2DM in Chinese population.

HDL signaling and protection against coronary artery atherosclerosis in mice

Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high density lipoprotein（HDL） are associated with reduced risk of atherosclerosis and preclinical,animal model studies demonstrate that this association is causative.Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics.Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall.These signaling responses require the HDL receptor,scavenger receptor class B type 1（SR-B1）,an adaptor protein（PDZK1） that binds to the cytosolic C terminus of SR-B1,Akt1 activation and（at least in endothelial cells） activation of endothelial NO synthase（eNOS）.Mouse models of atherosclerosis,exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice（apoE or LDLR KO） develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis.On the other hand,inactivation of each of the components of HDL signaling（above）in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.

Association between TaqIB polymorphism of cholesteryl ester transfer protein and coronary artery disease in the Chinese population

Objective: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. Methods: We searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The lit- erature search yielded 448 studies, in which 10 case-control studies including 1 694 cases and 1 456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89-1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09-1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers. Conclusions: In the present study, the TaqIB poly- morphism of CETP was found to be associated with CAD in the Chinese population.

Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores:evidence from the China Kadoorie Biobank

Background:Several studies have reported that polygenic risk scores(PRSs)can enhance risk prediction of coronary artery disease(CAD)in European populations.However,research on this topic is far from sufficient in non-European countries,including China.We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.Methods:Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training(n=28,490)and testing sets(n=72,150).Ten previously developed PRSs were evaluated,and new ones were developed using clumping and thresholding or LDpred method.The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set.Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms.Prediction of the 10-year first CAD events was assessed using hazard ratios(HRs)and measures of model discrimination,calibration,and net reclassification improvement(NRI).Hard CAD(nonfatal I21-I23 and fatal I20-I25)and soft CAD(all fatal or nonfatal I20-I25)were analyzed separately.Results:In the testing set,1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years.The HR per standard deviation of the optimal PRS was 1.26(95%CI:1.19-1.33)for hard CAD.Based on a traditional CAD risk prediction model containing only non-laboratory-based information,the addition of PRS for hard CAD increased Harrell’s C index by 0.001(-0.001 to 0.003)in women and 0.003(0.001 to 0.005)in men.Among the different high-risk thresholds ranging from 1%to 10%,the highest categorical NRI was 3.2%(95%CI:0.4-6.0%)at a high-risk threshold of 10.0%in women.The association of the PRS with soft CAD was much weaker than with hard CAD,leading to minimal or no improvement in the soft CAD model.Conclusions:In this Chinese population sample,the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD.Therefore,this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.

冠心病病人HDL-C/LDL-C、ApoA1/ApoB、Lp(a)变化及与冠脉病变程度支数的关系分析

目的:探究冠心病(CHD)病人高密度脂蛋白胆固醇/低密度脂蛋白胆固醇(HDL-C/LDL-C)、载脂蛋白A1/载脂蛋白B(ApoA1/ApoB)、脂蛋白a[Lp(a)]变化及与冠脉病变程度支数的关系。方法:选取冠心病病人90例作为CHD组,同期体检健康者100名作为对照组,比较2组及不同病变程度支数病人的HDL-C/LDL-C、ApoA1/ApoB及Lp(a)水平。结果:CHD组病人的HDL-C/LDL-C、ApoA1/ApoB水平低于对照组(P<0.01和P<0.05),Lp(a)水平高于对照组(P<0.05);90例CHD病人中,26例病人为单支病变,30例为双支病变,34例为多支病变,随着病变支数的增加,病人的HDL-C/LDL-C和ApoA1/ApoB水平呈降低趋势(P<0.01),Lp(a)水平呈升高趋势(P<0.01);Pearson相关性分析结果显示,病变支数与HDL-C/LDL-C、ApoA1/ApoB水平成负相关(r=-0.474、-0.501,P<0.01),与Lp(a)水平成正相关(r=0.379,P<0.01)。ROC结果显示,上述3项指标联合(并联)评估CHD病人双支及以上病变程度支数的AUC及敏感度均高于单一指标诊断(P<0.01),3项指标对诊断两支及以上病变的切点值分别为0.405、1.425、273.120 mg/L。结论:HDL-C/LDL-C、ApoA1/ApoB及Lp(a)水平与CHD病人冠状动脉病变程度支数密切相关,三者联合检测对评估CHD病人冠脉病变支数程度具有较高的价值相关性,建议临床密切监测。

Elevated plasma lipoprotein-associated phospholipase A2 activity is associated with plaque rupture in patients with coronary artery disease

Background Lipoprotein-associated phospholipase A2 （Lp-PLA2） has recently been shown to be positively related to coronary events in patients with coronary artery disease （CAD）. However, direct evidence about the relationship between circulation Lp-PLA2 activity and vulnerable plaque in patients with CAD remains lacking. Methods Plasma Lp-PLA2 activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound （IVUS）. Results Eighty-three patients were included in the final analysis after the initial screening. Sixty （72.3%） were acute coronary syndrome （ACS） patients and 23 （27.7%） were stable angina pectoris （SAP） patients. Plaque rupture occurred in 39 （47.0%） patients, and 34 （87.2%） were from ACS patients and 5 （12.8%） from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein （hs-CRP） level and Lp-PLA2 activity （all P 〈0.05）. IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling （74.4% vs. 43.2%, P=0.004）, soft plaques （64.1% vs. 36.4%, P=-0.012） and higher remodeling index （1.13~0.16 vs. 0.99＋_0.11, P=0.041） as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA2 activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque （Model 1： odds ratio （OR） 1.13, 95% confidence interval （CO ： 1.06-1.20） or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque （Model 2： OR 1.11,95%C1： 1.04-1.19）. Conclusions Plasma Lp-PLA2 activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA2 may be a risk marker for vulnerable plaques.

apoB与LDL-C评估冠心病风险的临床价值比较

目的探讨在载脂蛋白B(apoB)与低密度脂蛋白胆固醇(LDL-C)含量不一致情况下,比较apoB与LDL-C对冠心病风险评估的重要价值。方法将接受冠脉造影检查的患者作为研究对象,共603例,根据apoB、LDL-C中位数水平分为低值组和高值组,然后两两组合,共分为4组(低apoB/低LDL-C组,低apoB/高LDL-C组,高apoB/低LDL-C组,高apoB/高LDL-C组),根据冠状动脉造影结果评估冠脉病变支数及冠状动脉狭窄程度,探讨apoB与LDL-C与冠心病及其病变严重程度之间的关系。结果比较4组冠心病血管病变支、冠脉病变程度,差异明显存在统计学意义(P<0.05)。当LDL-C、apoB含量一致时,与低低组相比,高高组的冠脉病变支数及冠脉病变程度有统计学差异(P<0.05)。当apoB与LDL-C含量不一致时,与低低组相比,高apoB低LDL-C组冠脉病变支数明显增多(P=0.017),冠脉病变严重(P=0.034);而低apoB高LDL-C组冠脉病变支数及严重程度差异不明显(P>0.05)。采用Pearson相关性分析,LDL-C、apoB、均为冠心病的危险因子。比较LDL-C和apoB的ROC曲线下面积,LDL-C为0.579(P=0.014),而apoB为0.589(P=0.006)。结论在apoB与LDL-C不一致情况下,apoB与LDL-C均为冠心病的危险因子,与冠心病病变程度密切相关,且apoB与LDL-C相比,在预测冠心病风险上同样具有重要的指导意义。