The increased plasma Lp(a): B lipoprotein particle concentration in angina pectoris is not associated with hypofibrinolysis

The structural homology between plasminogen and apolipoprotein (a), the specific glycoprotein of Lp(a) lipoprotein, raises the possibility of a relationship between this lipoprotein and the plasma fibrinolytic system. The present study examines this proposal by studying 66 patients with angina pectoris. As compared to normal controls, the patients had raised concentrations of Lp(a): B lipoprotein particles. No correlation was found between circulating Lp(a): B and the fibrinolytic system. The pathogenic role of Lp(a): B lipoprotein seems therefore not mediated by its effect on the plasma fibrinolytic system.     

Association of lipoprotein(a) and apolipoprotein(a) phenotypes with coronary and carotid atherosclerosis in CHD men

AIM: To evaluate in a case-control cross-sectional study whether lipoprotein(a) concentration and apo(a) phenotypes are associated with the presence and severity of coronary and carotid atherosclerosis. MATERIALS AND METHODS: We have examined 198 male CHD patients (mean age 53 +/- 8) years) with stenosis more than 50% at least in one main coronary artery or its major branches. Duplex scanning was performed in 168 patients to assess the degree of carotid atherosclerosis. Seventy six apparently healthy men (mean age 39 +/- 9 years) formed the control group. Lp(a) concentration was measured by ELISA, apo(a) phenotyping was performed by immunoblotting. RESULTS: Lp(a) level was significantly higher in cases compared to controls: 37 +/- 31 mg/dl vs. 18 +/- 27 mg/dl, p < 0.05. Patients had low-molecular weight apo(a) phenotypes more frequently than controls: 46% vs. 29%, p = 0.01. Patients aged 45 years and younger had low-molecular weight apo(a) phenotypes more frequently than older ones (65% vs. 42%, p < 0.05) and controls (65% vs. 29%, respectively, p = 0.001). High Lp(a) level and low-molecular weight apo(a) phenotypes correlated with presence and number of coronary occlusions. CONCLUSION: There was association between Lp(a) level, low-molecular weight apo(a) phenotypes and presence, severity, extension of carotid atherosclerosis. No differences in distribution of other CHD risk factors among all subgroups of patients were found.     

Association of lipoprotein(a) concentration and apo(a) isoform size with restenosis after percutaneous transluminal coronary angioplasty

Lp(a) is a unique class of lipoprotein particles that exhibits a considerable size heterogeneity resulting from the size polymorphism of apo(a), its unique protein component. An elevated level of Lp(a) in plasma has been proposed to be a risk factor for premature development of coronary artery disease. To evaluate the relationship between Lp(a) concentration and apo(a) isoform size with restenosis after percutaneous transluminal coronary angioplasty, Lp(a) levels and apo(a) phenotypes were determined in 204 patients who underwent a successful coronary angioplasty procedure and stent implantation. The patients were followed with clinical examinations and exercise tests at 1, 3, and 6 months, and a control coronary angiography was performed after 6 months to evaluate restenosis. Lp(a) levels were determined with an ELISA that is insensitive to the size heterogeneity of Lp(a), and the apo(a) isoforms were determined by a high-resolution agarose gel electrophoresis method followed by immunoblotting with a specific monoclonal antibody. Of the 146 patients who underwent angiographic evaluation, 57 (39%) had restenosis, whereas 89 (61%) did not. Lp(a) levels and the distribution of the expressed apo(a) phenotypes were compared in these two groups of patients. Although the mean and median Lp(a) levels were higher in the restenosed group, the difference was not statistically significant. However, a significant difference in Lp(a) values was found in women (P=0.043), even though, because of the small number of women in the study (n=35), no sound conclusions can be reached on the predictive role of Lp(a) in restenosis. There also was no difference in the distribution of apo(a) phenotypes between the two groups. Because of their wide distribution, Lp(a) values and apo(a) isoforms do not seem to be a useful indicator of risk of restenosis after percutaneous transluminal coronary angioplasty in our study cohort.     

Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study

BACKGROUND: Recent reports have suggested an association of atherosclerosis with risk of venous thrombosis. OBJECTIVE: To confirm whether subclinical atherosclerosis is a risk factor for venous thrombosis (VT) among men and women age 65 and older. METHODS: Participants of the Cardiovascular Health Study (n = 4,108) without baseline clinical cardiovascular disease, anticoagulant use or previous VT were followed for a median of 11.7 years after non-invasive assessment of subclinical atherosclerosis using carotid ultrasound (intima-media thickness and presence of plaques), ankle-brachial blood pressure index and electrocardiogram. Each event was classified as idiopathic or secondary. We used Cox proportional hazards regression to estimate the relative risk of overall and idiopathic VT for individuals with and without baseline subclinical atherosclerosis. RESULTS: There were 133 first time VT events. No subclinical atherosclerosis measures were associated with increased risk of overall or idiopathic VT. The adjusted relative risks of overall and idiopathic VT for presence of any type of subclinical disease were 0.60 (95% confidence interval 0.39-0.91) and 0.32 (0.18-0.59), respectively. Most of this association was explained by an inverse association of high-risk carotid plaques (prevalent in 54% of those at risk) with VT. CONCLUSION: Non-invasively measured subclinical atherosclerosis was not associated with increased risk of overall or idiopathic VT in this observational study. Carotid plaques and arterial events during follow up were inversely associated, a finding that requires further study.     

Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men

Summary.  Aims : The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men. Methods : A prospective study of 3217 men aged 60–79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases. Results : Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers ( P  < 0.05) and marginally significant for fibrin D-dimer ( P  = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina. Conclusion : Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men.     

经皮冠状动脉介入导致ACS患者脂蛋白(a)和氧化脂蛋白(a)水平升高机制研究

目的 研究PCI治疗对ACS患者脂蛋白(a)[Lp(a)]、氧化脂蛋白(a)[ox-Lp(a)]水平的影响和机制.方法 收集75例ACS患者PCI前、后、24 h、2 d、3 d和6个月后各时间点,以及29例未行PCI术的对照组冠状动脉造影前、后血标本;采用ELISA法测定Lp(a)、OX-Lp(a)、Lp(a)免疫复合物[Lp(a)-IC]和自身抗体水平;冠状动脉造影确认病变程度.手术前后各指标的变化采用配对t检验;PCI前、后不同时间点Lp(a)、ox-Lp(a)相对变化值间比较采用方差分析;Lp(a)与ox-Lp(a)、冠状动脉病变程度与Lp(a)、ox-Lp(a)变化值间相关性采用直线相关分析.结果 PCI术后Lp(a)水平[233.10(152.86～328.79)mg/L]高于术前[202.05(106.15～271.42)mg/L],差异有统计学意义(数据经对数转换后分析,t=6.81,P<0.01);PCI术后ox-Lp(a)[19.05(10.98～31.80)mg/L]与术前[10.51(4.98～17.97)mg/L]相比升高,差异有统计学意义(数据经对数转换后分析,t=13.22,P<0.01);PCI术后Lp(a)-IC[2.72(1.60～4.91)AU]与术前[2.11(1.04～3.97)AU]相比升高,差异有统计学意义(数据经对数转换后分析,t=3.34,P<0.01);而PCI术后自身抗体(A=0.81±0.33)与术前(A=0.72±0.28)相比降低,差异有统计学意义(t=5.58,P<0.01).PCI前(r=0.66,P<0.01)、后(r=0.62,P<0.01)ox-Lp(a)水平均与Lp(a)高度相关.PCI导致Lp(a)、ox-Lp(a)水平急速升高,24 h内快速下降,2～3 d内接近术前水平.Lp(a)、ox-Lp(a)变化值均与冠状动脉病变程度呈正相关.对照组造影前后Lp(a)、ox-Lp(a)、Lp(a)-IC和Lp(a)自身抗体水平均无变化.结论 PCI导致ACS患者Lp(a)、ox-Lp(a)水平升高,其增加值与冠状动脉病变程度相关.     

Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS)

BACKGROUND: The TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene is associated with HDL-C, progression of coronary artery disease (CAD) and response to pravastatin treatment in men with angiographically proven CAD (REGRESS). We hypothesized that differences in CETP concentration could explain these associations and now investigated whether CETP concentration is an independent determinant of these parameters. MATERIALS AND METHODS: Plasma CETP concentrations at baseline and after 2 years' treatment with pravastatin or placebo were measured (n=674), and correlations with lipid and angiographic parameters (mean segment- and obstruction-diameter; MSD and MOD), and TaqIB genotype were studied. RESULTS: After segregation into three groups (baseline CETP<1.58, 1.58-2.21, >2.21 mg L(-1)), subjects with the highest CETP had significantly higher baseline total cholesterol, LDL-C and triglycerides (P<0.01), while HDL-C, MSD and MOD were not different among these groups. After 2 years of placebo, the MSD decreased threefold (P<0.001) and the MOD decreased 2.4-fold (P=0.042) more in the highest compared with the lowest CETP quartile. Pravastatin treatment reduced total cholesterol LDL-C and triglycerides significantly more in the highest CETP quartile. Moreover, only in the highest CETP quartile, pravastatin significantly reduced the MSD- (P=0.003) and MOD-decrease (P=0.014) compared with placebo, and, notably, this was independent of baseline lipids and differential lipid changes in these quartiles. Strikingly, baseline associations and treatment responses according to baseline CETP were independent of TaqIB genotype. CONCLUSIONS: High CETP concentration is associated with faster progression of coronary atherosclerosis in men with proven CAD. Second, pravastatin yielded the highest improvement of lipid and angiographic parameters in patients with high baseline CETP independent of baseline lipids, lipid changes and TaqIB genotype, indicating that the plasma CETP level itself is an important determinant of the response to statins.     

Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.

Elevated lipoprotein(a) (Lp[a]) concentrations are associated with premature coronary heart disease (CHD). In the general population, Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors also affect plasma Lp(a) levels. In addition, Lp(a) has been hypothesized to be an acute phase protein. It is therefore unclear whether the association of Lp(a) concentrations with CHD is primary in nature. We have analyzed apo(a) phenotypes, Lp(a) levels, total cholesterol, and HDL-cholesterol in patients with CHD, and in controls from the general population. Both samples were Chinese individuals residing in Singapore. Lp(a) concentrations were significantly higher in the patients than in the population (mean 20.7 +/- 23.9 mg/dl vs 8.9 +/- 12.9 mg/dl). Apo(a) isoforms associated with high Lp(a) levels (B, S1, S2) were significantly more frequent in the CHD patients than in the population sample (15.9% vs 8.5%, P less than 0.01). Higher Lp(a) concentrations in the patients were in part explained by this difference in apo(a) allele frequencies. Results from stepwise logistic regression analysis indicate that apo(a) type was a significant predictor of CHD, independent of total cholesterol and HDL cholesterol, but not independent of Lp(a) levels. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) levels, and firmly establish the role of Lp(a) as a primary genetic risk factor for CHD.     

Circulating secretory type IIA phospholipase A2, lipoprotein (a) and soluble cellular adhesion molecule levels in patients with angina pectoris

Objectives

To examine the plasma levels of secretory type IIA phospholipase A2 (sPLA₂-IIA), lipoprotein (a) [Lp(a)], soluble intercellular adhesion molecule-1 (sICAM-1) and soluble platelet endothelial CAM-1 (sPECAM-1), as well as ICAM-1 (K469E) and PECAM-1 (Leu125Val) gene polymorphisms, in patients with unstable angina pectoris (UAP) and stable AP (SAP).

Design and methods

We enrolled 75 patients with SAP, 72 with UAP and 80 controls without angina. Blood samples were obtained before angiography.

Results

The concentrations of sPLA₂-IIA, sICAM-1 and sPECAM-1 were higher for UAP patients than for SAP patients and controls, and the level of Lp(a) was higher for UAP patients than for controls. Lp(a) and sPLA₂-IIA levels were significantly correlated, and high plasma Lp(a) level (≥ 300 mg/L) was an independent risk factor for angina.

Conclusion

Lp(a) may play an important role in the development of angina. Further research should investigate the role of sPLA₂-IIA, sICAM-1 and sPECAM-1 in UAP.     

The association of serum lipoprotein(a) levels, apolipoprotein(a) size and (TTTTA)(n) polymorphism with coronary heart disease.

BACKGROUND: The association between lipoprotein(a) levels, apolipoprotein(a) size and the (TTTTA)(n) polymorphism which is located in the 5' non-coding region of the apo(a) gene was studied in 263 patients with severe coronary heart disease and 97 healthy subjects. METHODS: Lp(a) levels were measured by ELISA, apo(a) isoform size was determined by SDS-agarose gel electrophoresis, and analysis of the (TTTTA)(n) was carried out by PCR. For statistical calculation, both groups were divided into low (at least one apo(a) isoform with < or = 22 Kringle IV) and high (both isoforms with >22 KIV) apo(a) isoform sizes, and into low number (<10 in both alleles) and high number of (> or =10 at least one allele) TTTTA repeats. RESULTS: Lp(a) levels were higher (P=0.007), apo(a) isoforms size < or =22 KIV and TTTTA repeats > or = 10 were more frequent (P=0.007 and 0.01) in cases than in controls. Lp(a) levels were found to be increased with low apo(a) weight in both groups (both P<0.0001). In multivariate logistic regression analysis, only the Lp(a) levels (P=0.005) and (TTTTA)(n) polymorphism (P=0.002) were found to be significantly associated with CHD. CONCLUSION: Nevertheless, these results indicate that in CHD patients the (TTTTA)(n) polymorphism has an effect on Lp(a) levels which is independent of the apo(a) size.     

参附注射液对冠心病心绞痛患者氧化型低密度脂蛋白和一氧化氮水平的影响

背景内皮功能障碍与冠心病之间的关系越来越受到重视.氧化型低密度脂蛋白(ox-LDL)及一氧化氮(NO)的改变对内皮功能产生一定的影响,对冠心病患者的预后起着重要的作用,中药在治疗此类疾病时对这些指标的改善起到哪些作用呢?目的观察参附注射液对冠心病心绞痛患者ox-LDL及NO的影响.设计随机对照的研究.单位解放军第二○五医院内二科,锦州医学院附属第一医院心血管内科.对象解放军第二○五医院,锦州医学院附属第一医院住院及心血管专科门诊收治的冠心病心绞痛患者60例.方法60例冠心病心绞痛患者随机分为对照组和治疗组,两组均予西药常规治疗,治疗组加用参附注射液静滴.分别检测两组治疗前后血清ox-LDL和NO水平.主要观察指标治疗后两组患者ox-LDL及NO水平变化情况.结果对照组治疗前后ox-LDL,NO的值分别为(6.01±0.81),(5.78±0.55)μg/L;(11.39±1.15),(12.89±1.80)μmol/L,其变化差异无显著性意义(P＞0.05),而治疗组治疗前后上述两指标的值则分别为(6.61±0.87),(4.01±0.82)μg/L;(11.83±1.25),(17.20±1.52)μmol/L,差异有显著性意义(P＜0.05).结论参附注射液可升高冠心病心绞痛患者NO水平、降低ox-LDL水平,从而改善血管内皮功能.     

Association of serum lipoprotein(a) concentration with other cardiovascular risk factors in a Chinese population.

The association between serum Lp(a) concentration, a risk factor for atherothrombotic disease, and other cardiovascular risk factors such as smoking, alcohol intake, hypertension, obesity, and indices of glycemic control is examined in a cohort of 313 elderly Chinese subjects (M = 160, mean age +/- SD = 68 +/- 11 year; F = 153, mean age +/- SD = 73 +/- 11). Although associations existed for the above risk factors and other serum lipid levels, there was no association with serum Lp(a) concentration in the overall population. Men with Lp(a) greater than or equal to 30 mg/dl had a higher mean age and blood pressure. A higher percentage of subjects with Lp(a) greater than or equal to 30 mg/dl had a family history of stroke, although the total number of those with a family history was too small to reach statistical significance. The lack of association with known modifiable cardiovascular risk factors is compatible with the conclusion that Lp(a) concentration is primarily under genetic control and therefore unlikely to be a modifiable risk factor.     

Clinical course of disease and prognosis in patients with ischemic heart disease with stable angina pectoris,caused by stenosing coronary atherosclerosis (data from a a 20-year study

AIM: To study a course and prognosis of ischemic heart disease (IHD) with stable angina pectoris (SAP) caused by stenotic coronary atherosclerosis (SCA) by 20-year follow-up data. MATERIAL AND DATA: Prognosis of survival was made in 318 patients with SAP due to SCA. RESULTS: The results of a 20-year study show that prognosis in IHD patients depends on SAP severity (by the functional class), exercise tolerance (by the exercise test), severity of coronary bed affection and of left ventricular contractility affection as assessed by coronary- and ventriculography. If lethality of the test subjects was not higher than in the population, the patient had good prognosis associated with one-vessel lesion, normal myocardial contractile function, high exercise tolerance, absence of the leading risk factors. CONCLUSION: The multivariance analysis with stepwise selection enabled the design of the model of the integral prognostic index (IPI) for the studied patients. The IPI index under 1.86 suggests a favourable prognosis, 1.87-2.33--an intermediate prognosis and in IPI higher than 2.34--unfavourable prognosis. Early surgery is recommended for patients with high IPI.     

Effect of red wine consumption on lipoprotein (a) and other risk factors for atherosclerosis

Epidemiological studies have pointed to the role of alcohol,and red wine in particular, in reducing the incidence of coronaryheart disease. This study attempted to distinguish, in vivo,the effects of components specific to red wine and those ofalcohol on lipoproteins, antioxidant status and membrane fluidity.Volunteers (n=20) were given 200 ml of red wine per day for10 days. Following a 6-week washout, this was repeated withwhite wine. Changes within treatment groups were analysed bypaired t tests and repeated measures analysis of variance wasused to distinguish effects of red wine components and alcohol.LDL was prepared by ultracentrifugation and all other assayswere by conventional laboratory techniques. No effect with eithertreatment was detected on total cholesterol, triglycerides,HDL or measures of antioxidant status, including the susceptibilityof LDL to oxidation. Red wine reduced LDL cholesterol (p<0.01),and both treatments reduced LDL apo B (p<0.01) and increasedLDL chohapo B ratio (p<0.01), implying an increase in LDLsize. Potential anti-atherogenic changes specific to red winewere reduction in lipoprotein (a) (p< 0.001) and increasedmembrane fluidity (p<0.01). These results are not in keepingwith the proposed role of red wine components in free-radicalprotection, but the reduction in lipoprotein (a) merits furtherinvestigation.     

脂蛋白(a)颗粒浓度评估原发性高血压患者心血管风险的临床价值[1]

摘要：目的?通过分析原发性高血压患者血清脂蛋白(a)[Lp(a)]颗粒浓度与质量浓度，探讨血清Lp(a)水平对高血压患者心血管疾病风险评估的预测价值。方法?选取122例原发性高血压患者，按照中国高血压防治指南分为高风险组96例、低风险组26例；分别检测血清Lp(a)颗粒浓度、质量浓度以及血脂等其他生化参数。采用多元Logistic回归分析血清Lp(a)颗粒浓度、质量浓度对高血压患者心血管疾病风险分层的预测比值比(OR)及其95%置信区间(CI)。结果?高风险高血压患者的血清Lp(a)颗粒浓度27.7(8.58，64.65)nmol/L、质量浓度148.00(54.00，338.50)mg/L均高于低风险患者5.80(2.75，14.53)nmol/L、42.50(23.75，84.00)mg/L，P均<0.001。相关性分析显示，高血压患者血清Lp(a)颗粒浓度、质量浓度呈正相关(r=0.979，P<0.001)，均与HDL-C浓度呈负相关(r=-0.233，P=0.012及r=-0.233，P=0.013)。多因素Logistic回归分析显示，血清Lp(a)颗粒浓度(OR=1.105，95%CI=1.017～1.199，P=0.018)、质量浓度(OR=1.016，95%CI=1.003～1.030，P=0.016)的升高与高血压患者心血管疾病风险的增高相关。结论?高心血管疾病风险的原发性高血压患者血清Lp(a)颗粒浓度、质量浓度高于低风险患者；Lp(a)颗粒浓度有望成为高血压患者心血管疾病风险分层体系的辅助指标。