Low density lipoprotein metabolism in hypertriglyceridemic and normolipidemic patients with coronary heart disease

The turnover rates of low density lipoprotein-apolipoprotein B (LDL-apoB) were determined in 32 men with coronary heart disease (CHD) and 11 control men with normal plasma lipids. Thirty patients with CHD had normal levels of LDL-cholesterol (LDL-C); of these patients, 9 had hypertriglyceridemia and 21 had normal plasma lipids. Mean concentrations of total cholesterol and LDL-C were similar among the control subjects and CHD patients, although the latter had significantly lower HDL-C. In control subjects, transport rates and fractional catabolic rates (FCR) of LDL-B were 10.6 +/- 0.5 (SEM) mg/kg-day and 0.31 +/- 0.01 pools/day, respectively. In 10 hypertriglyceridemic patients with CHD, transport rates were 21.7 +/- 1.7 mg/kg-day, and FCRs averaged 0.56 +/- 0.06 pools/day; both were significantly higher than normal (P less than 0.05). Six normolipidemic patients also had abnormally high transport rates of LDL-apoB (19.4 +/- 2.8 mg/kg-day) and FCRs (0.51 +/- 0.03 pools/day); again both were higher than normal. The remaining 16 normolipidemic patients with CHD had normal transport rates (9.9 +/- 0.6 mg/kg-day) and FCRs (0.28 +/- 0.01 pools/day). Thus, hypertriglyceridemic patients with CHD and a portion of normolipidemic patients with CHD were characterized by increases in both transport and fractional catabolic rate of LDL-apoB; these abnormalities in LDL metabolism may have contributed to their coronary heart disease. However, the majority of normolipidemic patients with CHD did not show a distinct defect in their LDL metabolism.     

幽门螺杆菌感染对冠心病患者冠状动脉病变程度与血清Ghrelin/obestatin比值的影响

目的探讨幽门螺杆菌(Helicobacter pylori,H.pylori)感染与冠心病患者冠状动脉病变程度和血清Ghrelin/obestatin比值之间的关系。方法选取2013年1月至2014年10月行冠状动脉造影确诊冠心病患者116例作为冠心病组,选取同期健康体检人员80例作为对照组。对所有患者的冠状动脉病变程度进行Gensini评分,运用14 C尿素呼气试验方法测定H.pylori感染情况,测定血清Ghrelin和obestatin水平,分析H.pylori感染与冠状动脉病变程度、血清Ghrelin/obestatin比值之间的关系。结果冠心病组H.pylori感染阳性率明显高于对照组,差异有统计学意义(P0.05)。H.pylori感染阳性组Gensini积分明显高于H.pylori感染阴性组,差异有统计学意义(P0.05);H.pylori感染阳性组Ghrelin/obestatin比值明显低于H.pylori感染阴性组,差异有统计学意义(P0.05)。结论 H.pylori感染能够加重冠心病患者冠状动脉病变程度,引起Ghrelin/obestatin比值异常升降低。H.pylori感染与冠心病发生发展密切相关。     

测定冠心病患者血清HDL-C和LDL-C水平的方法学比较

目的:比较超速离心法、电泳法、匀相法、沉淀法在干扰因素存在时检测冠心病(CHD)患者血清胆固醇水平的特异性。方法:采用超速离心法、电泳法、匀相法及沉淀法对150例CHD患者和102例健康体检者分别进行血清胆固醇水平的测定,比较各方法之间的相关性,同时分析导致结果差异的因素。结果:四种方法检测健康人群HDL-C、LDL-C水平,结果间无统计学差异(P>0.05);CHD组,当TG≤2.26mmol/L时,采用沉淀法和匀相法检测CHD患者血清LDL-C,结果差异较小(P>0.05),电泳法检测结果偏高,与沉淀法、电泳法间有统计学差异(P<0.05)。超速离心法与电泳法间的相关性良好,但匀相法及沉淀法易受高胆红素、高血红蛋白等因素的影响。结论:超速离心法虽耗时、价格贵,但仍为检测HDL-C、LDL-C的经典方法,电泳法受高胆红素、血红蛋白、高三酰甘油等干扰因素的影响相对较小,适用于冠心病HE合并高血脂血清HDL-C、LDL-C水平检测。     

Immunoglobulin E and matrix metalloproteinase-9 in patients with different stages of coronary artery diseases

The aims of this study were to identify levels of total immunoglobulin E (IgE) and matrix metalloproteinase (MMP)-9 in patients with different stages of coronary artery diseases. IgE, MMP-9, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride (TG) were measured by fluorescence enzyme immunoassay, gelatin zymography, and autoanalyzer in normal subjects (n = 40), patients with stable angina pectoris (SAP, n = 40), patients with unstable angina pectoris (UAP, n = 40), patients with acute myocardial infarction (AMI, n = 40), or post-CABG-surgery of those acute myocardial infarction (P-CABG, n = 40). Compared with normal subjects, increased IgE but unchanged MMP-9, CPK, LDH were found in SAP group and UAP group, whereas IgE, MMP-9, CPK and LDH levels were all significantly increased in AMI group. IgE, MMP-9, CPK and LDH levels in P-CABG group were significantly reduced, compared with AMI group, and were similar to those in normal subjects. Cholesterol, LDL, HDL and TG were not significantly changed in all groups. We suggest that serum total IgE can be an early marker of coronary artery disease and MMP-9 is a marker of acute myocardial infarction.     

Preoperative prediction of significant coronary artery disease in patients with valvular heart disease.

A prognostic index for predicting significant coronary artery disease was established using multiple logistic regression analysis of clinical data from 643 patients with valvular heart disease who had undergone routine coronary arteriography before valve replacement. The index or equation obtained incorporated the presence of angina, a family history of ischaemic heart disease, age, cigarette smoking habits, mitral valve disease, sex, and electrocardiographic evidence of myocardial infarction. The equation was validated using prospective data from 387 patients with valvular disease and shown to enable almost a third of routine coronary arteriograms to be omitted while maintaining 95% sensitivity for patients with coronary artery disease. Similar analysis of the more detailed prospective data produced a second discriminant function incorporating diastolic blood pressure, total cigarettes smoked in life, the severity of angina, family history of ischaemic heart disease, age, current cigarette smoking habits, and the ratio of total to high density lipoprotein cholesterol. This method improved the discrimination between patients with and without coronary artery disease, allowing omission of 30% of routine coronary arteriograms with 100% sensitivity for patients with coronary disease and omission of 41% with a 96% sensitivity level.     

Increased oxidazability of plasma low density lipoprotein from patients with coronary artery disease

Oxidative modification of lipoproteins may play a crucial role in the pathogenesis of atherosclerosis. This study was designed to examine whether increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins occur in patients with coronary artery disease. The levels of lipid peroxides, estimated as thiobarbituric acid-reactive substances (TBARS), were significantly greater in the plasma and very low density lipoprotein (VLDL) of symptomatic patients with coronary artery disease than in those of healthy persons, but the TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) showed insignificant difference between patients and normals. To evaluate the oxidative susceptibility of lipoproteins, we employed in vitro Cu²⁺ oxidation of lipoproteins monitored by changes in fluorescenece, TBARS level, trinitrobenzene sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel electrophoretic mobility. While VLDL and LDL of normal controls were oxidazed at 5–10 μM Cu²⁺, pooled VLDL and LDL of patients with coronary artery disease were oxidized at 1–2.5 μM Cu²⁺, i.e., at relatively lowver oxidative stress. At 5 μM Cu²⁺, VLDL and LDL of patients with coronary artery disease still showed at faster oxidation rate, judged by the rate of fluorescence increase, higher TBARS level, less TNBS reactivity, greater change in apo B immunoreactivity and higher electrophoretic mobility than those of normal controls. However, the difference on the oxidizability of HDL was insignificant for patients vs. normals. In conclusion, we have shown that plasm VLDL and LDL of patients with coronary artery disease are more susceptible to in vitro oxidative modification than those of health persons. The data suggest that enhanced oxidizability of plasma lipoproteins may be important factor influencing the development of coronary artery disease.     

Super-ego in patients with coronary artery disease

In this paper, we explored the super-ego ofpatients with coronary artery disease. Research results have confirmed the initial hypothesis that a significant number of patients with coronary artery disease has rigorous super-ego. Among patients with coronary artery disease (N=50), and control group (N=50), we have found significant differences in the quality of super-ego and ego attitude towards the demands of the super-ego. The results of this research contribute to understanding the impact of psychological factors in coronary artery disease.     

High plasma leptin levels are associated with impaired diastolic function in patients with coronary artery disease

Background and aimsObese subjects have elevated leptin levels, which have been associated with increased risk of cardiovascular events. Because leptin has direct cellular effects on various tissues, we tested the hypothesis that leptin levels are associated with cardiac structure or function in patients with coronary artery disease (CAD).Methods and resultsThe study population consisted of 1 601 CAD patients, of whom 42% had type 2 diabetes mellitus. Plasma leptin was measured in fasted state and an echocardiography performed. Leptin levels were not related to LV dimensions or LV ejection fraction (NS for all), but higher leptin levels were associated with elevated E/E’ (9.43 vs. 11.94 in the lowest and the highest leptin quartile, respectively; p = 0.018 for trend). Correspondingly, a decreasing trend was observed in E/A (1.15 vs. 1.06; p = 0.037). These associations were independent of obesity and other relevant confounding variables.ConclusionWe conclude that elevated plasma leptin levels are associated with impaired left ventricular diastolic function in patients with CAD independently of obesity and other confounding variables. Leptin may be one of the mechanistic links explaining the development of congestive heart failure in obese subjects.     

Increased plasma HB-EGF associated with obesity and coronary artery disease

The mechanism by which the obese subjects are more associated with vascular disease remains unclear. We reported that the adipose tissues produce and secrete many bioactive molecules, conceptualized as adipocytokines. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), produced locally by vascular macrophages and smooth muscle cells, has been suggested to induce the migration and proliferation of vascular smooth muscle cells. The current study reveals that (1) HB-EGF mRNA is abundantly expressed in human adipose tissue, (2) HB-EGF mRNA increases in the fat tissues of obese mice, (3) plasma HB-EGF levels increase in parallel with fat accumulation in human, and (4) the subjects with coronary artery disease have higher plasma HB-EGF levels, associated with fat accumulation. These results suggest that increased plasma HB-EGF derived from the accumulated fat contributes to the higher incidence of vascular disease in obesity, proposing HB-EGF as an adipocytokine directly linking adipovascular axis.     

Extracellular vesicles with ubiquitinated adenosine A2A receptor in plasma of patients with coronary artery disease

Extracellular vesicles (EV) can transfer cellular molecules for specific intercellular communication with potential relevance in pathological conditions. We searched for the presence in plasma from coronary artery disease (CAD) patients of EV containing the adenosine A_2A receptor (A_2AR), a signalling receptor associated with myocardial ischaemia and whose expression is related to homocysteine (HCy) metabolism. Using protein organic solvent precipitation for plasma EV preparation and Western blotting for protein identification, we found that plasma from CAD patients contained various amounts of EV with ubiquitin bound to A_2AR. Interestingly, the presence of ubiquitinated A_2AR in EV from patients was dependent on hyperhomocysteinemia, the amount being inversely proportional to A_2AR expression in peripheral mononuclear cells in patients with the highest levels of HCy. CEM, a human T cell line, was also found to released EV containing various amounts of ubiquitinated A_2AR in stimulated conditions depending on the hypoxic status and HCy level of culture medium. Together, these data show that ubiquitinated A_2AR‐containing EV circulate in the plasma of CAD patients and that this presence is related to hyperhomocysteinemia. A_2AR in plasma EV could be a useful tool for diagnosis and a promising drug for the treatment of CAD.     

Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patients

Homocysteine, cytokines (IL-18, IL-6, IL-8) are involved in vascular inflammation and coronary artery disease. Homocysteine influences endothelial IL-6 and IL-8 cytokine expression and release, however, an association between homocysteine and IL-18 has not been previously investigated in endothelial/smooth muscle cells and or in coronary artery disease. We report in 9 coronary artery bypass surgery (CABG) patients a positive correlation r = 0.86 between homocysteine and IL-18 plasma levels (p < 0.05). Plasma IL-18 levels are significantly higher in those patients with elevated homocysteine compared to those with normal levels (p < 0.02; 153 +/- 19 pg/ml versus 116 +/- 14 pg/ml respectively). Our in vitro cell culture studies suggest that the source of IL-18 in CABG patients with elevated homocysteine is not from vascular smooth muscle or endothelial cells.     

冠心病患者幽门螺杆菌感染与血清Ghrelin、同型半胱氨酸水平的相关性研究

目的探讨冠心病患者幽门螺杆菌(Helicobacter pylori,H.pylori)感染与血清Ghrelin、同型半胱氨酸(Hcy)水平的相关性。方法选择2013年1月至2014年12月行冠状动脉造影确诊冠心病患者136例作为冠心病组,另选择同期健康体检人员60例作为对照组。运用14 C尿素呼气试验方法测定H.pylori感染情况,观察组患者的冠状动脉病变程度进行Gensini评分,测定血清Ghrelin和Hcy水平,分析H.pylori感染与Ghrelin、Hcy水平及Gensini积分之间的关系。结果冠心病组血清Ghrelin水平明显低于对照组,差异有统计学意义(t=10.65,P0.05);冠心病组血清Hcy水平明显高于对照组,差异有统计学意义(t=6.08,P0.05)。冠心病患者中,H.pylori感染组血清Ghrelin明显低于H.pylori未感染组,差异有统计学意义(t=7.58,P0.05);H.pylori感染组组血清Hcy明显高于H.pylori未感染组,差异有统计学意义(t=5.63,P0.05)。随着冠心病H.pylori感染程度的加重,血清Ghrelin水平逐渐下降,血清Hcy水平、Gensini积分逐渐升高。H.pylori感染根治后血清Ghrelin水平较治疗前明显升高,而Hcy水平明显下降,差异均有统计学意义(t=14.84、6.25,P0.05)。结论 H.pylori感染能够影响冠心病患者血清Ghrelin、Hcy水平,H.pylori感染可能参与冠心病发生发展。H.pylori感染程度与冠心病患者冠状动脉病变程度相关。     

Clinical implication of coronary tortuosity in patients with coronary artery disease

BackgroundCoronary tortuosity (CT) is a common coronary angiography finding. The exact pathogenesis, clinical implication and long-term prognosis of CT are not fully understood. The purpose of this study is to investigate the clinical characteristics of CT in patients with suspected coronary artery disease(CAD) in a Chinese population.MethodsA total of 1010 consecutive patients underwent coronary angiography with complaints of chest pain or related symptoms were included in the present study (544 male, mean age: 64±11 years). CT was defined by the finding of ≥3 bends (defined as ≥45° change in vessel direction) along main trunk of at least one artery in systole and in diastole. Patients with or without CAD were further divided into CT-positive and CT-negative groups, all patients were followed up for the incidence of major adverse cardiovascular events (MACE) for 2 to 4 years.ResultsThe prevalence of CT was 39.1% in this patient cohort and incidence of CT was significantly higher in female patients than that in male patients (OR = 2.603, 95%CI 1.897, 3.607, P<0.001). CT was positively correlated with essential hypertension (OR = 1.533, 95%CI 1.131, 2.076, P = 0.006) and negatively correlated with CAD (OR = 0.755, 95%CI 0.574, 0.994, P = 0.045). MACE during follow up was similar between CAD patients with or without CT.ConclusionsCT is more often seen in females and positively correlated with hypertension and negatively correlated with coronary atherosclerosis.     

Effects of altitude on exercise level and heart rate in patients with coronary artery disease and healthy controls

Background. To evaluate the safety and effects of high altitude on exercise level and heart rate in patients with coronary artery disease compared with healthy controls. Methods. Eight patients with a history of an acute myocardial infarction (ejection fraction >5%) with a low-risk score were compared with seven healthy subjects during the Dutch Heart Expedition at the Aconcagua in Argentina in March 2007. All subjects underwent a maximum exercise test with a cycle ergometer at sea level and base camp, after ten days of acclimatisation, at an altitude of 4200 m. Exercise capacity and maximum heart rate were compared between groups and within subjects. Results. There was a significant decrease in maximum heart rate at high altitude compared with sea level in both the patient and the control group (166 vs. 139 beats/min, p<0.001 and 181 vs. 150 beats/min, p<0.001). There was no significant difference in the decrease of the exercise level and maximum heart rate between patients and healthy controls (-31 vs. -30%, p=0.673). Conclusion. Both patients and healthy controls showed a similar decrease in exercise capacity and maximum heart rate at 4200 m compared with sea level, suggesting that patients with a history of coronary artery disease may tolerate stay and exercise at high altitude similarly to healthy controls. (Neth Heart J 2010;18:118-21.)     

Effects of residential exercise training on heart rate recovery in coronary artery patients

The aims of the present study are twofold: 1) to investigate whether heart rate recovery (HRR) after a cycle ergometry test is affected by exercise training and 2) to test the ability of HRR to replicate the baroreflex sensitivity (BRS) changes that occur in response to an exercise training program in coronary artery patients. We randomized 82 coronary artery patients undergoing a residential cardiac rehabilitation program to an exercise training group (TR; n = 43) and an untrained group (UTR; n = 39). All of the patients underwent an exercise test before and after the rehabilitation program. HRR was recorded at the end of the 1st and 2nd min after exercise. BRS was determined at rest before and after treatment. HRR after the 2nd min was significantly improved in TR patients (-21.4 +/- 0.9 beats/min) compared with UTR patients (-17.8 +/- 1.2 beats/min) at the end of the training program. Improvement in HRR paralleled that in BRS in TR patients (from 3.2 +/- 0.3 to 5.3 +/- 0.8 ms/mmHg; P < 0.001), whereas no significant change was evident in UTR patients (from 3.5 +/- 0 to 4.0 +/- 0.4 ms/mmHg; P = 0.230). Our data show that HRR in the 2nd min after the cessation of a cycle ergometer exercise test increased in coronary artery patients after an exercise training period. This result confirms the positive effect induced by exercise training on HRR and extends the conclusions of previous studies to different modalities of exercise (i.e., cycle ergometer). HRR might provide an additional simple marker of the effectiveness of physical training programs in cardiac patients.