The Interaction between Coagulation Factor 2 Receptor and Interleukin 6 Haplotypes Increases the Risk of Myocardial Infarction in Men

The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R) and the interleukin 6 (IL6) haplotypes modulates the risk of myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP). Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R) were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S), indicates the presence of a synergy (S>1) or of an antagonism (S<1). None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI) of 1.58 (1.05–2.41) (p = 0.02) in the crude and an OR of 1.72 (1.11–2.67) (p = 0.01) in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI) of 2.24 (1.27–3.95) (p = 0.005) and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI) of 1.56 (1.02–2.37) (p = 0.03) and S of 1.66 (0.89–31). In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.     

载脂蛋白AI—CⅢ基因区域DNA多态性及单倍型与冠心病的关系

本文利用重组DNA技术,以人apoAI cDNA片段为探针,对50例正常血脂汉族个体和33例冠心病患者的载脂蛋白AⅠ—CⅢ基因区域DNA多态频率和特征进行了分析。发现中国汉族群体载脂蛋白AⅠ—CⅢ基因区域亦存在Sst-Ⅰ和Msp-Ⅰ多态位点,可产生S_2和M_22种多态片段,其等位基因频率分别为0.167和0.22,均高于高加索人但低于日本人,表明这2个多态部位的等位基因频率具有种族差异。我们还对44例正常血脂个体和27例冠心病患者进行了单倍型分析,没有发现S_1S_2M_1M_1,S_2S_2M_1M_2和S_2S_2M_1M_1基因型个体,因此,在中国汉族人群中,可能仅存在3种单倍型:S_1—M_1(0.81),S_2M_2(0.17)及S_1—M_2(0.02),而不存在S_2—M_1这种单倍型。同日本人和高加索一样,在中国汉族人群中,S_1S_2与M_1、M_2之间亦存在连锁不平衡。本研究结果表明,S_2与M_2等位基因在正常血脂的汉族人与冠心病病人之间的分布频率均没有显著差异,但冠心痛病人的S_1—M_2单倍型频率明显高于正常人,其有极显著的差异。提示S_1—M_2这种单倍型与冠心病有明显的关联,可做为一种假定的动脉粥样硬化致病基因的连锁标记,对有关个体进行连锁分析。     

Serum CD121a (Interleukin 1 Receptor,Type I): A Potential Novel Inflammatory Marker for Coronary Heart Disease

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1β, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79–2.72], 2.67 (95% CI: 1.47–4.84), and 4.71 (95% CI: 2.65–8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70–3.14), 2.25 (95% CI: 1.10–4.62), and 4.39 (95% CI: 2.19–8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1β levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD.     

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease

Molecular Diagnosis & Therapy - Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery...     

Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease

Objective

To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.

Methods

Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.

Results

Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.

Conclusion

Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects.     

Signature of Circulating MicroRNAs as Potential Biomarkers in Vulnerable Coronary Artery Disease

Aims

MicroRNAs (miRNAs) play important roles in the pathogenesis of cardiovascular diseases. Circulating miRNAs were recently identified as biomarkers for various physiological and pathological conditions. In this study, we aimed to identify the circulating miRNA fingerprint of vulnerable coronary artery disease (CAD) and explore its potential as a novel biomarker for this disease.

Methods and Results

The Taqman low-density miRNA array and coexpression network analyses were used to identify distinct miRNA expression profiles in the plasma of patients with typical unstable angina (UA) and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). Significantly elevated expression levels of miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126*, and miR-451 were observed in UA patients compared to controls. These findings were validated by real-time PCR in another 45 UA patients, 31 stable angina patients, and 37 controls. In addition, miR-106b, miR-25, miR-92a, miR-21, miR-590-5p, miR-126* and miR-451 were upregulated in microparticles (MPs) isolated from the plasma of UA patients (n = 5) compared to controls (n = 5). Using flow cytometry and immunolabeling, we further found that Annexin V⁺ MPs were increased in the plasma samples of UA patients compared to controls, and the majority of the increased MPs in plasma were shown to be Annexin V⁺ CD31⁺ MPs. The findings suggest that Annexin V⁺ CD31⁺ MPs may contribute to the elevated expression of the selected miRNAs in the circulation of patients with vulnerable CAD.

Conclusion

The circulating miRNA signature, consisting of the miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126* and miR-451, may be used as a novel biomarker for vulnerable CAD.

Trial Registration

Chinese Clinical Trial Register, ChiCTR-OCH-12002349.     

白细胞介素23 受体基因rs6682925 多态与冠心病发病的相关关系

目的:本研究探讨白细胞介素23受体(Interleukin 23 Receptor,IL23R)基因单核苷酸多态位点(rs1884444与rs6682925)与中国北方汉族人群冠心病发病的相关关系。方法:本研究采用病例-对照的设计方法,收集568名冠心病患者以及45岁以上、年龄及性别匹配的524名正常对照个体为研究对象,采用测序法检测IL23R rs1884444与rs6682925单核苷酸多态性基因型,分析IL23R基因rs1884444与rs6682925单核苷酸多态位点的基因型及等位基因的分布情况。结果:IL23R rs6682925与rs1884444单核苷酸多态位点的基因型频率符合Hardy-Weinberg定律。IL23R基因rs6682925单核苷酸多态位点的三种基因型分布频率(CC型,TC型和TT型)在冠心病组为22.9%,39.6%和37.5%,在对照组分别为41.7%,47.2%和11.1%,IL23R基因rs6682925单核苷酸多态位点C等位基因是冠心病发病的一个独立的危险因素(P0.05);IL23R基因rs1884444单核苷酸位点的基因型和等位基因的频率在对照组和冠心病组之间不存在统计学差异(P0.05)。Logistic回归校正性别、年龄、体重指数、吸烟、高血压、高脂血症、糖尿病等冠心病的易患因素后,IL23R基因rs6682925 C等位基因仍是冠心病发病一个独立危险因素。结论:在中国北方汉族人群中,IL23R基因rs6682925 C等位基因可能是冠心病发病的独立危险因素。     

Relationship between Inflammatory Cytokines and Uric Acid Levels with Adverse Cardiovascular Outcomes in Patients with Stable Coronary Heart Disease

Background

So far it is unclear whether the association between serum uric acid (SUA), inflammatory cytokines and risk of atherosclerosis is causal or an epiphenomenon. The aim of the project is to investigate the independent prognostic relationship of inflammatory markers and SUA levels with adverse cardiovascular outcomes in a patient population with stable coronary heart disease (CHD).

Methods

SUA, C-reactive protein (CRP) and interleukin (IL)-6 were measured at baseline in a cohort of 1,056 patients aged 30–70 years with CHD. Cox proportional hazards model was used to determine the prognostic value of these markers on a combined CVD endpoint during eight year follow-up after adjustment for covariates.

Results

For 1,056 patients with stable coronary heart disease aged 30–70 years (mean age 58.9 years, SD 8.0) follow-up information and serum measurements were complete and n = 151 patients (incidence 21.1 per 1000 patients years) experienced a fatal or non-fatal CVD event during follow-up (p-value = 0.05 for quartiles of SUA, p = 0.002 for quartiles of CRP, p = 0.13 for quartiles of IL-6 in Kaplan-Meier analysis). After adjustment for age, gender and hospital site the hazard ratio (HR) for SUA increased from 1.37 to 1.65 and 2.27 in the second, third, and top quartile, when compared to the bottom one (p for trend <0.0005). The HR for CRP increased from 0.85 to 0.98 and 1.64 in the respective quartiles (p for trend 0.02). After further adjustment for covariates SUA still showed a clear statistically significant relationship with the outcome (p for trend 0.045), whereas CRP did not (p for trend 0.10).

Conclusion

The data suggest that compared to inflammatory markers such as CRP and IL-6 serum uric acid levels may predict future CVD risk in patients with stable CHD with a risk increase even at levels considered normal.     

冠状动脉介入治疗对冠心病患者Caspase-3,9 水平的影响

目的:通过对冠心病患者经皮冠状动脉介入治疗(PCI)前后血清Caspase-3,9水平变化的观察,探讨冠状动脉介入治疗对冠心病患者血清Caspase-3,9水平的影响。方法:冠状动脉介入组(PCI组)30例和单纯造影组(CAG组)29例,在术前0.5h,术后3h,术后6h,术后12h,术后24h,术后48h分别测定血清Caspase-3,9水平。结果:CAG组术前与术后的血清Caspase-3,9水平差异均无统计学意义,PCI组术后3h、6h的Caspase-3水平较术前0.5h均有降低趋势,差异均有统计学意义(P<0.05),PCI组术后48h的Caspase-9水平与术后3h、6h相比均有升高趋势,差异均有统计学意义(P<0.05)。结论:PCI术后狭窄或闭塞的冠状动脉血管重新恢复血供,血清中Caspase-3,9水平在PCI术后先降低后又逐渐升高,提示再灌注后可出现细胞的凋亡程度加重,血清中Caspase-3,9的水平可作为心肌再灌注损伤后细胞凋亡程度的评估指标并可作为诊断临床症状不典型的再灌注损伤的一个指标。PCI术可有效改善心肌血供,减少因术前缺血缺氧造成的细胞凋亡,但PCI术后再灌注损伤可进一步加重细胞凋亡。     

Association of Plasma Resistin Levels with Coronary Heart Disease in Women

Objective: To examine the association between plasma resistin levels and the presence of coronary heart disease (CHD) in women. Research Methods and Procedures: Plasma resistin levels were measured in a case‐control study including 185 women with angiographically confirmed CHD and 227 population‐based female controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) study. Results: After adjustment for age, smoking, family history of myocardial infarction, retirement, education, physical activity, menopausal status, hormone replacement use, BMI, hypertension, diabetes, and dyslipidemia, the odds ratio for CHD for women in the highest compared with lowest quintile of plasma resistin levels was 3.19 (95% confidence interval, 1.44 to 7.10; p log trend, 0.001). After additional adjustment for plasma C‐reactive protein levels, this association was substantially attenuated and no longer significant (odds ratio, 1.80; 95% confidence interval, 0.69 ti 4.69; p trend = 0.23). Discussion: These results suggest that plasma resistin levels are significantly associated with the presence of CHD in women; however, this association can largely be explained by concomitant inflammatory processes. Further studies are needed to determine the causal role of resistin in the development of CHD in humans.     

冠状动脉介入治疗对冠心病患者Caspase-3,9水平的影响

目的：通过对冠心病患者经皮冠状动脉介入治疗（PCI）前后血清Caspase-3,9水平变化的观察,探讨冠状动脉介入治疗对冠心病患者血清Caspase-3,9水平的影响。方法：冠状动脉介入组（PCI组）30例和单纯造影组（CAG组）29例,在术前0.5h,术后3h,术后6h,术后12h,术后24h,术后48h分别测定血清Caspase-3,9水平。结果：CAG组术前与术后的血清Caspase-3,9水平差异均无统计学意义,PCI组术后3h、6h的Caspase-3水平较术前0.5h均有降低趋势,差异均有统计学意义（P〈0.05）,PCI组术后48h的Caspase-9水平与术后3h、6h相比均有升高趋势,差异均有统计学意义（P〈0.05）。结论：PCI术后狭窄或闭塞的冠状动脉血管重新恢复血供,血清中Caspase-3,9水平在PCI术后先降低后又逐渐升高,提示再灌注后可出现细胞的凋亡程度加重,血清中Caspase-3,9的水平可作为心肌再灌注损伤后细胞凋亡程度的评估指标并可作为诊断临床症状不典型的再灌注损伤的一个指标。PCI术可有效改善心肌血供,减少因术前缺血缺氧造成的细胞凋亡,但PCI术后再灌注损伤可进一步加重细胞凋亡。     

冠心病患者冠脉支架术后发生再狭窄的危险因素回归分析

目的:探讨冠心病患者冠脉支架手术后发生再狭窄的危险因素,为提高临床治疗效果和改善预后提供指导。方法:回顾性分析2014年1月至2015年12月我院收治的226例行冠脉支架手术的冠心病患者临床病历资料,采用SPSS21.0分析冠脉再狭窄的发生情况及危险因素。结果:51例冠心病患者冠脉支架术后发生冠脉再狭窄(22.57%)。单因素分析显示,不同吸烟史、糖尿病史、脂蛋白a(Lp(a))水平、空腹血糖、尿素氮(BUN)、总胆红素、术前病变狭窄程度、植入支架支数、长度以及直径组冠心病患者的冠脉再狭窄发生率比较,差异有统计学意义(P0.05)。多因素Logistic回归分析,吸烟史、糖尿病史、Lp(a)水平、术前病变狭窄程度、植入支架支数、长度是冠心病患者冠脉支架术后再狭窄发生的独立危险因素,OR分别为2.261、1.944、3.593、2.798、2.449、3.823,差异有统计学意义(P0.05),植入支架直径是冠脉再狭窄发生的保护因素,OR为0.261,差异有统计学意义(P0.05)。结论:冠脉植入支架的总长度、数量,术前病变的狭窄程度、Lp(a)水平、糖尿病以及吸烟是冠心病患者冠脉支架术后发生再狭窄的独立危险因素,临床应不断优化支架并根据再狭窄的危险因素采取针对性的防治措施。     

冠心病患者胰岛素抵抗程度的影响因素分析

目的:分析冠心病患者胰岛素抵抗程度的影响因素。方法:选择我院收治的冠心病住院患者166例,根据胰岛素抵抗指数(HOMA-IR)水平将其分成四组。A组:HOMA-IR≤1.53(n=36);B组:1.53HOMA-IR≤3.46(n=30);C组:3.46HOMA-IR≤5.13(n=36);D组:HOMA-IR≥5.14(n=64)。检测和比较各组一般临床资料和相关生化指标的差异,并进一步分析影响冠心病患者胰岛素抵抗程度的危险因素。结果:C、D组腰围、空腹血糖(FBG)、餐后2 h血糖(2 h PBG)、低密度脂蛋白胆固醇(LDL-C)均高于A、B组;D组空腹胰岛素(INS)均高于A、B组,B、C组INS、LDL-C均高于A组;D组体质量、TC高于A组。上述差异均有统计学意义(P0.05)。多因素分析结果显示BMI、腰臀比(WHR)、FBG、INS、TC、HDL-C均是HOMA-IR的影响因素(P0.05)。结论:体重、腰围、FBG、2h PBG、INS、TC、HDL-C的上升均为加重冠心病患者胰岛素抵抗程度的危险因素。     

Meta-Analysis of RAGE Gene Polymorphism and Coronary Heart Disease Risk

Background

Recent data from human and animal studies have shown an upregulated expression of advanced glycosylation end product–specific receptor (RAGE) in human atherosclerotic plaques 1 and in retina, messangial, and aortic vessels, suggesting an important role of RAGE in the pathogenesis of atherothrombotic diseases. In the past few years, the relationship between RAGE polymorphisms (−429T/C, −374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; however, these studies have yielded contradictory results.

Methods

PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between RAGE polymorphisms and susceptibility to CHD. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

A total of 17 studies including 4343 patients and 5402 controls were involved in this meta-analysis. Overall, no significant results were observed for −429T/C (OR  = 1.01, 95% CI: 0.92–1.12, P  = 0.78), −374T/A (OR  = 1.11, 95% CI: 0.98–1.26, P  = 0.09) and G82S (OR  = 1.12, 95% CI: 0.86–1.45, P  = 0.41) polymorphism. In the stratified analyses according to ethnicity, sample size, CHD endpoint and Hardy-Weinberg status, no evidence of any gene-disease association was obtained.

Conclusions

This meta-analysis demonstrates that there is no association between the RAGE −429T/C, −374T/A and G82S polymorphisms and CHD.     

女性冠心病患者的危险因素分析及与冠脉病变严重程度的关系

目的:了解女性冠心病患者的危险因素及与冠脉病变严重程度的关系。方法:随机选取本院2012年至2014年心血管科住院治疗的疑似冠心病女性患者150例,经冠脉造影确诊冠心病患者105例,非冠心病患者45例。对患者的临床资料和冠脉病变严重程度进行单因素和多因素分析。结果:冠心病患者高血压与糖尿病百分比、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)及纤维蛋白原水平均高于非冠心病患者,而高密度脂蛋白(HDL-C)和血红蛋白水平均低于非冠心病患者(P0.05);年龄、高血压与糖尿病百分比、血脂上升百分比(高TC、高TG、低HDL-C、高LDL-C)、高尿酸百分比和纤维蛋白原水平均随冠状动脉病变支数及Gensini积分的增加而增加(P0.05);多因素分析发现女性冠心病的影响因素分别为高LDL-C、糖尿病、低HDL-C、TG和高血压,其中高LDL-C的影响最为显著(P0.05)。结论:高血压、糖尿病史、血脂水平为女性冠心病的影响因素,其中高LDL-C的影响最显著,各影响因素均与冠脉病变程度紧密相关。     

冠心病患者TNF-a 水平及其基因多态性的研究

为了研究中国汉族人群中血清肿瘤坏死因子-a（TNF-a）水平及其-857、-863位点基因多态性与冠心病之间的相关性, 采用双抗体夹心ELISA法检测血清TNF-a水平,同时应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测TNF-a基因多态性。 冠心病组血清TNF-a水平显著高于对照组（P<0.05）,-863 位点基因多态性在两组间分布有显著差异(P<0.05),-857位点分布无差异。血清TNF-a水平显著升高提示炎性反应在冠心病病程中有重要作用,TNF-a的水平受其基因多态性的影响。     

Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular Events

Background

The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE) estimates the burden of cardiovascular risk in renal transplant recipients (RTR). Our recent study of 95 RTR reported the 7-year median risk of cardiovascular events (CVE) to be 9.97%, ranging from 1.93 to 84.27%. Nearly a third (28.4%) of the cohort was above 20% risk for a CVE. Since interleukins (ILs) as part of the inflammatory response may play a role in the pathogenesis of cardiovascular disease (CVD), we extended this study to identify which ILs are associated with high cardiovascular risk in this population.

Methods

Twenty-two ILs were measured by multiplexed fluorescent bead-based immunoassay in 95 RTR and 56 normal controls. Stepwise analysis after multivariate determination of significant demographic and inflammatory variables was performed between the high and low-CVD risk groups (which were arbitrarily set at scores <10% and ≥20%, respectively). Normalized data was presented as mean ± SD and non-normalized data as median (minimum–maximum). Significance was measured at <0.05.

Results

27.5% of the low-risk and 31.3% of the high-risk groups had mean IL levels above the 95 percentile of the normal control levels. In the non-parametric analysis IL-6, 9, 16, 17 and 33 were significantly higher in the high-risk group compared to the control. Univariate analysis (UVA) of the high-risk group identified IL-33 as the only IL that remained significantly higher than the control and low-risk groups (p = 0.000). The percentage of patients with IL-33 levels above the 90 percentile of control value in the low and high-risk groups were 15.6% and 52.0%, respectively (p<0.002). UVA of factors significant to high IL-33 levels included estimated glomerular filtration rate (eGFR), while diabetes mellitus, serum phosphorus, microalbuminuria and age also remained significant in the multivariate analysis.

Conclusion

Circulating IL-33 level is positively associated with high CRCRTR-MACE score. Diminished eGFR, age, diabetes, serum phosphorus and microalbuminurea demonstrate significant relationship with elevated IL-33 levels, supporting the possible pathognomonic role of IL-33 in the cardiovascular burden in RTR.     

OSAS对冠心病患者的血糖和血脂水平的影响

目的:探讨阻塞性睡眠呼吸暂停综合征(Obstructive sleep apnea syndrome,OSAS)对冠心病患者血糖和血脂的影响。方法:纳入我科住院的明确诊断冠心病患者共168人,根据呼吸暂停低通气指数(Apnea-hypopnea index,AHI)共分2组:冠心病组133例,冠心病合并OSAS组45例(轻度OSAS组16例;中度OSAS组18例,重度OSAS组12例)。对比分析冠心病组和冠心病合并OSAS组患者血脂及血糖水平及其相关性。结果:BMI、LDL、HDL在四组间差异有统计学意义(P0.05)。冠心病合并OSAS的BMI、LDL、HDL明显高于冠心病组,各组间BMI差异有统计学意义(P0.05)。FPG、HOMA-I、RHb A1、OX-LDL、AHI在冠心病组和冠心病合并轻度OSAS组之间差异无统计学意义(P0.05)。FPG、HOMA-I、RHb A1、OX-LDL、AHI在OSAS轻、中、重各组间差异有统计学意义(P0.05)。冠心病合并OSAS患者AHI和BMI、LDL、FPG、HOMA-I、OX-LDL呈正相关关系(P0.05)。结论:OSAS增加了冠心病患者血脂水平和糖尿病的风险,及机制可能与胰岛素抵抗和OX-LDL水平增高有关。     

Association of Small Dense LDL Serum Levels and Circulating Monocyte Subsets in Stable Coronary Artery Disease

Objective

Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.

Methods

We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.

Results

Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.

Conclusion

The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.     

Excess Weight and the Risk of Incident Coronary Heart Disease Among Men and Women

Overweight and obesity have been prospectively associated with the risk of coronary heart disease (CHD). Less clear is the relation of excess weight to risk of CHD among men and women with comorbid conditions, and the proportion of CHD risk attributable to excess weight in the US population. To assess the risk of CHD associated with excess weight among men and women with and without associated comorbid conditions, and determine the population attributable risk of CHD associated with excess weight. The study population consisted of two prospective cohorts, the Health Professionals Follow‐up Study (HPFS) (N = 42,351 men; age range at baseline, 39–75 years) and the Nurses' Health Study (NHS) (N = 76,703 women; age range at baseline, 39–65 years). A total of 2,771 incident cases of CHD among the men and 2,359 among the women were documented over the 16 years of follow‐up. Overall, the relative risk (RR) of CHD associated with BMI ≥30 kg/m² compared with BMI 18.5–22.9 kg/m² was 2.13 (95% confidence interval (CI), 1.82–2.48) among the men and 2.48 (95% CI, 2.20–2.80) among the women. The risk of CHD increased with BMI, both with and without the presence of comorbid conditions. Our estimates suggest that more than a third of all incident CHD in US men and women may be attributed to excess weight. Excess weight is associated with increased risk of CHD among men and women, both alone and in combination with comorbid conditions, though the results require careful interpretation. A substantial proportion of incident CHD may be attributed to excess weight.