Left ventricular function during graded exercise in patients with coronary artery disease and in control subjects.

The left ventricular function of 30 patients with coronary artery disease and 11 control subjects was studied by electrocardiography gated cardiac blood pool scintigraphy as the participants lay on their backs and either rested or exercised on a cycle ergometer at graded levels on intensity. The control subject showed a progressive increase in ejection fraction from rest (51% +/- 7%) to intermediate (56% +/- 10%, P less than 0.05) and maximum levels of exercise (64% +/- 10%, P less than 0.001). All the patients showed a decrease in ejection fraction from rest (42% +/- 16%) to their maximal level of exercise (36% +/- 11%, P less than 0.001). However, the response of some of the patients to intermediate exercise ranged from a decrease or no change to an increase in ejection fraction. Thus, exercise at maximal intensity is necessary to induce the left ventricular dysfunction that is diagnostic of coronary artery disease.     

Exercise training improves conduit vessel function in patients with coronary artery disease.

It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8 (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8 to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1 +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.     

Probing the epigenetic signatures in subjects with coronary artery disease

Depletion of S-adenosyl methionine and 5-methyltetrahydrofolate; and elevation of total plasma homocysteine were documented in CAD patients, which might modulate the gene-specific methylation status and alter their expression. In this study, we have aimed to delineate CAD-specific epigenetic signatures by investigating the methylation and expression of 11 candidate genes i.e. ABCG1, LIPC, PLTP, IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66 and TGFBR3. The methylation-specific PCR and qRT-PCR were used to assess the methylation status and the expression of candidate genes, respectively. CAD patients showed the upregulation of IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66, and TGFBR3. Hypomethylation of CDKN2A loci was shown to increase risk for CAD by 1.79-folds (95% CI 1.22–2.63). Classification and regression tree (CART) model of gene expression showed increased risk for CAD with F2RL3?>?3.4-fold, while demonstrating risk reduction with F2RL3?<?3.4-fold and IL-6?<?7.7-folds. This CAD prediction model showed the excellent sensitivity (0.98, 95% CI 0.88–1.00), specificity (0.91, 95% CI 0.86–0.92), positive predictive value (0.82, 95% CI 0.75–0.84), and negative predictive value (0.99, 95% CI 0.94–1.00) with an overall accuracy of 92.8% (95% CI 87.0–94.1%). Folate and B₁₂ deficiencies were observed in CAD cases, which were shown to contribute to hypomethylation and upregulation of the prime candidate genes i.e. CDKN2A and F2RL3. Early onset diabetes was associated with IL-6 and TNF-α hypomethylation and upregulation of CDKN2A. The expression of F2RL3 and IL-6 (or) hypomethylation status at CDKN2A locus are potential biomarkers in CAD risk prediction. Early epigenetic imprints of CAD were observed in early onset diabetes. Folate and B₁₂ deficiencies are the contributing factors to these changes in CAD-specific epigenetic signatures.

     

Influence of exercise training on spatial R-wave amplitude in patients with coronary artery disease

To evaluate the influence of an exercise program on spatial and left precordial R-wave amplitude among patients with coronary artery disease, computerized electrocardiogram (ECG) data were acquired during maximal treadmill testing before and after 1 yr in 89 patients randomized to either exercise (n = 40) or control (n = 49) groups. Spatial and lateral R-wave amplitudes were derived from the orthogonal Frank (XYZ) lead system. The exercise group significantly increased maximal O2 consumption (0.17 l/min), whereas controls decreased significantly (0.12 l/min, P less than 0.01 between groups). No significant changes in electrocardiographic R-wave voltage measurements occurred within or between groups during the year. It is concluded that exercise training does not result in increases in R-wave voltage in patients with 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.     

Pentoxifylline administration changes protein expression profile of coronary artery disease patients

Increased level of inflammatory mediators plays a central role in the features of coronary artery diseases. As pentoxifylline could suppress the inflammatory process and has shown some promising beneficial effects in inflammatory diseases, we evaluated the effect of two months pentoxifylline administration in proteome of PBMCs of patients with coronary artery disease (CAD). A randomized placebo-controlled study was used. Fourteen CAD patients were randomized to 2 months of pentoxifyline treatment (1200 mg/day) (n = 7) or placebo treatment (n = 7). Blood samples were obtained before and after treatment. A comparative 2 dimensional gel electrophoresis was performed, and gels were silver-stained. Differentially expressed protein spots were detected and were identified by MALDI-TOF spectrometry. Six differentially expressed proteins were identified as HSP70, PPIA and α-Enolase, (all up-regulated) S100-A9, PIMT and β-5 tubulin (all down-regulated), most of which had previously been shown to play a potential role in the pathogenesis of atherosclerosis. As the blood mononuclear cell proteome responds to pentoxifylline with changes in a number of atherosclerosis-relevant proteins, it seems that pentoxifylline could be a good choice for future studies for prevention of cardiovascular events.     

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.     

Coronary artery calcium findings in asymptomatic subjects with family history of premature coronary artery disease

ABSTRACT: BACKGROUND: To evaluate the frequency of positive coronary arteries calcium (CAC) scores in a unique population of asymptomatic first degree relatives (FDRs) of patients with angiographically confirmed early onset of coronary artery disease (CAD) and to assess their association with carotid ultrasound findings and other cardiovascular risk factors. Method and Results: We scanned, using 64-slice multi-detector computed tomography, 57 asymptomatic FDRs (47+9 years old; 44% male, 56% female), out of the 111 FDRs previously phenotyped for cardiovascular (CV) risk factors. The controls were 616 individuals (57+10 years old; 76% male, 24% female) with no family history of cardiovascular disease, chest pain or diabetes selected out of the 3500 subjects scanned between 2002 and 2007. FDRs had higher risk of abnormal CAC scores compared to controls; odds ratio (OR) for the 75th percentile was 1.96 (95%CI 1.04 - 3.67, p<0.05). CONCLUSION: The frequency of abnormal CAC scores is two-fold higher in asymptomatic FDRs than in controls. CAC scan provides additional information on CV risk assessment in asymptomatic FDRs, particularly for those in the intermediate risk category. Clinical Trial Registration: NCT00387595.     

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.     

Cardioprotective effects of adenosine transport inhibition during reversible ischaemia in patients with coronary artery disease

BACKGROUND: Adenosine plays a major role in protecting ischaemic myocardium and may potentiate ischaemic preconditioning. Nucleosine transport inhibition may enhance these favourable effects. DESIGN: Randomized, double blind, placebo controlled study, to investigate the haemodynamic and cardioprotective effects of nucleoside transport inhibition during ischaemia in patients with coronary artery disease. PATIENTS AND METHODS: Elective left anterior descending (LAD) coronary angioplasty was used to produce reversible ischaemia in 24 patients with stable angina and a single LAD lesion. They were randomized to receive either the nucleoside transport inhibitor draflazine or placebo. The study medication was infused between the 2nd and 3rd balloon inflation. The primary endpoint was ischaemia-induced wall motion abnormalities as measured by left septal echo amplitude, which was plotted against time to produce an area under the curve. RESULTS: No differences were observed in the systemic haemodynamics or the myocardial collateral circulation of the two groups. The ischaemia-induced regional wall motion abnormalities improved significantly after draflazine, while no difference was observed in the placebo group. This improvement was even more pronounced in patients with low caffeine levels compared with those with high caffeine levels. CONCLUSIONS: Draflazine, in the dose and route used, is associated with a significant improvement in regional myocardial function of the ischaemic area, without affecting systemic or collateral circulation, when compared with placebo. This implies that draflazine has a cardio-protective effect in ischaemic myocardium. High caffeine blood levels reduce these effects.     

Identification of patients with coronary artery disease using magnetocardiographic signal analysis.

INTRODUCTION: Magnetocardiography (MCG), which measures the magnetic component of the heart's electrical activity, offers an alternative approach for analyzing changes induced by coronary artery disease (CAD). This study examines several parameters that quantify spatial and temporal aspects of cardiac magnetic signals in CAD. MATERIALS AND METHODS: MCGs were registered at rest in 144 subjects, aged 58.3 +/- 9.8 years: 50 healthy subjects, 43 CAD patients without myocardial infarction (MI), 36 with MI, and 15 with spontaneous episodes of ventricular tachycardia (VT). Spatial characteristics of magnetic field maps (MFM), quantified using their centers of gravity, included MFM orientation and trajectory plots. Spatio-temporal analysis was performed by determining the spatial distribution of the QT interval. RESULTS: In CAD patients, MFM orientation during the QT interval deviated from normal in 67% of patients without MI and in 85% of patients with MI. Trajectory plots deviated from those of the normal group, with deviation increasing with disease severity. Quantifying the distribution of QT interval duration using a smoothness index demonstrated a significant difference between the values for healthy subjects and non-MI patients, as well as MI patients with and without VT (p < 0.001). CONCLUSION: The results reported demonstrate that disturbances in cardiac electrogenesis resulting from CAD may be assessed using MCG signal analysis.     

冠心病患者运动致QRS延长的临床意义

为探讨冠心病病人由于急性心肌缺血对ＱＲＳ持续时间变化的影响及其意义。本文收集了５３例病人,均进行运动试验和冠脉造影,其中２０例经冠脉造影排除心病,其他３３例经冠脉造影确定为冠心病。结果运动使冠脉正常者ＱＲＳ持续时间缩短,而使冠心病者ＱＲＳ持续时间延长。     

Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease

A cholesterol-rich emulsion (LDE) that resembles the LDL lipidic structure is taken-up by LDL receptors after intravenous injection by means of apolipoprotein E it acquires in the circulation and can be used to probe LDL metabolism. In this study, LDE was labeled with [14C]cholesteryl oleate and [3H]cholesterol and injected into 19 patients with coronary artery disease (CAD) and into 14 subjects without CAD to verify whether the kinetic behavior of the radioactive lipids is different in CAD. Blood was sampled over 24 h for radioactivity measurement after lipid extraction and separation by thin-layer chromatography. Fractional clearance rate (FCR, in h-1) of [14C]cholesteryl ester was not different in CAD and nonCAD expressed as median (25%; 75%): 0.08 (0.062; 0.134) h-1 versus 0.06 (0.04; 0.083) h-1, P = 0.167. However, [3H]cholesterol FCR was greater in CAD than in nonCAD (mean +/- SEM): 0.163 +/- 0.016 h-1 versus 0.077 +/- 0.014 h-1, P < 0.001. Esterification of the LDE [3H]cholesterol was also greater in CAD subjects than nonCAD at 10 h and 24 h after emulsion injection (P = 0.029 and 0.024 respectively). In conclusion, both removal from the plasma and esterification of the LDE-cholesterol were increased in CAD. These findings may contribute for unraveling pro-atherogenic mechanisms and the establishment of novel CAD markers.     

Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease

Plasma high density lipoproteins (HDL) can be separated into two subpopulations of apolipoprotein A-I-containing particles: those that also contain apoA-II [Lp(AI w AII)] and those that do not [Lp(AI w/o AII)]. These particles were isolated by immunoaffinity chromatography from 17 men (9 normolipidemic (NL), 8 hyperlipidemic (HL) with symptomatic coronary artery disease (CAD), from 17 NL men without any symptoms of CAD (healthy controls), and from 10 NL men with entirely normal coronary arteriograms (CAD-free controls). The distributions of particle size in these two subpopulations were determined by gradient gel electrophoresis and densitometric scanning. Approximately half of the Lp(AI w AII) particles in all subjects were distributed in the 8.2-9.2 nm interval. For patients with CAD, a greater fraction of the particles were small, in the 7.0-8.2 nm interval [33% in CAD vs. 26% in CAD-free controls (P less than 0.01) and 19% in healthy controls (P less than 0.0001)], and a smaller fraction of the particles were in the 9.2-11.2 nm interval (14% in CAD vs. 24% in CAD-free control (P less than 0.002) and healthy control groups (P less than 0.001). The Lp(AI w/o AII) of both control groups were primarily composed of two discrete subpopulations in the 8.2-9.2 nm and the 9.2-11.2 nm intervals. In CAD patients there were fewer particles in the 9.2-11.2 nm size interval (23% in CAD vs. 33% in CAD-free controls (P less than 0.005) and 36% in healthy controls (P less than 0.0001), and more particles in the smallest 7.0-8.2 nm size interval (32% in CAD vs. 23% in CAD-free controls (P less than 0.01) and 18% in healthy controls (P less than 0.001]. Thus, the spectrum of HDL particle sizes in patients with CAD tends to be shifted toward the smaller particle when compared with the two control groups. This was observed in both NL and HL patients with HDL cholesterol (CH) values in the normal range. As a group, CAD patients had lower HDL (42 +/- 7 mg/dl) and HDL2 (6 +/- 4 mg/dl) CH than healthy (HDL: 49 +/- 7, HDL2: 12 +/- 6 mg/dl) and CAD-free (HDL: 51 +/- 9, HDL2: 12 +/- 6 mg/dl) controls. When controls and patients were compared for their frequencies of abnormal HDL CH levels and particle sizes, abnormalities in HDL and HDL2 CH levels were not significantly more frequent (twofold) among CAD patients than among controls.(ABSTRACT TRUNCATED AT 400 WORDS)