Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Prevalence of extracranial carotid and vertebral artery disease in Chinese patients with coronary artery disease

Electrotonic responses recorded extra- or intracellularly from peripheral nerve preparations show a "sag" to hyperpolarizing current pulses. The biophysical nature of this "inward rectification" is still under discussion since the phenomenon has not been noted at voltage-clamped single nerve fibres, and since Cs+, which reduces inward rectification, is not a specific ion channel blocker. In this study, we found that low micromolar concentrations of ZD 7288, a specific blocker of the hyperpolarization-activated cationic current (Ih) in the soma of central mammalian neurons, result in a complete block of inward rectification in the electrotonic responses of isolated rat spinal dorsal roots. In addition, ZD 7288 enhanced the activity-dependent slowing of conduction seen in compound C fibre action potentials of isolated rat vagus nerves and augmented the post-tetanic hyperpolarization following trains of action potentials in unmyelinated and myelinated axons. The data suggest that ZD 7288 is a potent blocker and a useful research tool for the study of hyperpolarization-activated inward rectification (Ih) of peripheral nerve preparations.     

Major depression in patients with closed head injury.

Interviewed 120 patients with closed head injury (CHI) with regard to depressive symptoms at least 2 yrs after the date of injury. 92 Ss met Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria for major depressive disorder. Half of the depressed CHI Ss did not manifest depressive symptoms until at least 6 mo after being injured. Bipolar affective disorder and schizophrenia were uncommon following CHI. CHI patients may be at increased risk for development of major depressive disorder. CHI patients should be screened for depressive symptoms after they appear to have made a "full" recovery. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correct utilization of exercise electrocardiographic leads in differentiation of men with coronary artery disease from patients with a low likelihood of coronary artery disease using peak exercise ST-segment depression

In this study we compared the diagnostic characteristics of the individual exercise electrocardiographic leads, 3 different lead sets comprising standard leads and the effect of the partition value in the detection of coronary artery disease (CAD). The diagnostic variable used was ST-segment depression at peak exercise, and the study population consisted of 101 patients with CAD and 100 patients with a low likelihood of the disease. The lead system used was the Mason-Likar modification of the standard 12-lead system and exercise tests were performed on a bicycle ergometer. The comparisons were performed by means of receiver-operating characteristic analysis and by determining sensitivities at a fixed 95% specificity. These properties, defined here as diagnostic capacity, were the most efficacious in leads I, -aVR, V4, V5, and V6. Diagnostic capacities in leads aVL, aVF, III, V1, and V2 were quite poor; statistical comparisons indicated significant differences between these leads and lead V5 (p < or = 0.0001 in each case). Use of the maximum value of ST-segment depression at peak exercise derived from all 12 leads produced a considerable decrease in the diagnostic capacity of the exercise electrocardiogram compared with lead V5. The exclusion of leads aVL, V1, and III improved the diagnostic capacity compared with the 12-lead set, but it was still smaller than that of lead V5. With use of a lead set with the 5 best leads increased the diagnostic capacity over other lead sets and over any individual lead. Further improvement was noted when a 50% smaller partition value was applied to leads I and -aVR than for the other leads (p = 0.041). In conclusion, this study suggests that use of leads I, -aVR, V4, V5, and V6 is the most influential when differentiating between patients with CAD and patients with a low likelihood of disease using peak exercise ST-segment depression. The effective use of leads I and -aVR requires the partition value applied for these leads to be 50% smaller than that used for the lateral precordial leads.     

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.     

ST-segment depression and R-amplitude changes during bicycle stress test in patients with coronary artery disease (author's transl)

56 patients were examined with bicycle stress tests. Sensitivity and specificity of ST-segment depression were compared with R-wave amplitude changes. All patients had a coronary angiography because of suspected coronary artery disease (CAD). The specificity of ST-segment depression was 71%, for R-wave amplitude changes 50%. The sensitivity for ST-segment depression was 76% and for R-wave amplitude changes 50%. In addition in 7 patients with angiographically demonstrated CAD repeated stress tests were done. The ST-segment changes were nearly constant in all examinations, whereas the R-wave amplitude in V5 in 5 out of 7 patients changed considerably between decrease and increase. Considering these intraindividual changes, it seems doubtful whether the evaluation of the R-wave amplitude proves to be an improvement of the non-invasive diagnostic procedures of CAD.     

Prevalence and effects of cardiac rehabilitation on depression in the elderly with coronary heart disease

Stellate ganglion block (SGB) is considered to increase blood flow to the governing area, but recent studies have shown the decrease of common carotid arterial blood flow in the unblocked side following SGB. We investigated the influence of SGB on bilateral cerebral blood flow and oxygenation using a regional oxygen saturation (rSO2) monitor, TOS-96 (TOSTEC, Japan). The changes of blood volume (hemoglobin index: Hb I) and rSO2 were measured in twenty adult patients who underwent SGB at the transverse process of the C 6 vertebra. Prior to the investigation, two sensors were calibrated and placed on either side of each patient's forehead in order to see the difference. There were significant increases in rSO2 and Hb I in the blocked side and decreases in rSO2 and Hb I in the contralateral side. These results suggest that blood flow in the blocked side following SGB increases with decreased blood flow in the unblocked side. Patients with cerebral vascular disease undergoing SGB might be at risk of a decrease in cerebral blood flow in the unblocked area.     

Haemodynamic effects of dobutamine in patients with coronary artery disease

The Femininity Study was administered tl 31 alcoholic females, 146 college females, and 152 female schizophrenic patients. The data were factor analyzed: five major factors were identified: (1) heterosexual social role inadaptability; (2) parental role inadaptability; (3) homemaker role inadaptability; (4) general affective (neurotic) instability; and (5) maternal role inadaptability. The institutionalized women showed much greater incidence of all types of inadaptability.     

Factors influencing smoking cessation in patients with coronary artery disease

The nature of an innate cellular resistance to HSV-1 of cultured murine oligodendrocytes (OLs) in three strains of mice (C57BL/6J, Balb/cByJ and A/J) was investigated. The expression of immediate early (ICP4), early (ICP8) and late (gC) antigens in primary OL cultures was studied using an indirect immunofluorescence (IF) technique. HSV-1 infected OLs from C57BL/6J mice showed no viral antigens at 24 h post infection (p.i.) but rather a marked delay in antigen expression beginning at 60 h p.i. In contrast all three proteins were expressed in A/J OLs at 24 h p.i. while Balb/cByJ OLs showed an intermediate protein expression pattern. These results suggest that the innate cellular resistance to HSV-1 is determined prior to the expression of immediate early viral antigens. To further study these differences, the adsorption capacity between the three mouse strains was compared using dextran purified, [3H]thymidine labelled virus. No differences in HSV-1 adsorption were identified. Results from viral penetration studies approached statistical significance suggesting that penetration may be impaired in C57BL/6J and Balb/cByJ OLs when compared to A/J OLs and is likely fusion independent. The selective differences in HSV-1 resistance mediated by OLs, reflect differences in virus host cell interactions, that likely contribute to differences in mortality, viral spread, and the ability of virus to induce central nervous system (CNS) demyelination.     

Triglyceride levels in sons of patients with coronary artery disease

We describe a patient with perforated appendicitis who postoperatively suffered repeated episodes of shaking chills and temperature spikes. Initial blood cultures yielded growth of Flavobacterium meningosepticum, Pseudomonas putida and Pseudomonas paucimobilis, and succeeding blood cultures growth of Pseudomonas acidoverans. These bacteria in combination led to a suspicion of self-inoculation of contaminated water through an intravenous catheter. Antibiotic treatment had no effect on the symptoms, which only ceased when the intravenous catheter was removed.     

Dyslipidemia and coronary artery disease. Prevalence and treatment in patients referred for coronary arteriography

We report a case with adult respiratory distress syndrome (ARDS) associated with increased levels of squamous cell carcinoma-related antigen (SCC) in the serum and bronchoalveolar lavage fluid (BALF). ARDS was likely induced by ibuprofen, based on the presence of pancytopenia and a weakly positive drug lymphocyte stimulating test (DLST). High serum and BALF levels of interleukin (IL)-8, neutrophil elastase as well as SCC were detected. Corticosteroid therapy resulted in clinical improvement, resolution of pulmonary infiltrates on chest roentgenogram and normalization of serum and BALF levels of IL-8, neutrophil elastase and SCC.     

Prevalence of coronary artery disease and peripheral artery disease in patients with different types of primary hyperlipidemia

The prevalence of coronary artery disease (CAD) and peripheral artery disease (PAD) was studied in 280 (203 males, 77 females) patients with different types of primary hyperlipoproteinemia. In primary hyperbetalipoproteinemia the prevalence of CAD (45% for Type IIa and 47% for Type IIb) is significatly higher than that in the other types of hyperlipoproteinemia (38% for Type IV and 17% for Type V). On the other hand, PAD prevalence is much higher in hypertriglyceridemia (21% in Type IIb and 20% in Type V) than in hypercholesterolemia alone (9% in Type IIa). These results suggest ths atherosclerotic complications are concerned. Moreover, the high frequency of PAD found in hypertriglyceridemia can be related to the high occurrence of diabetes in these patients. The effects of other major risk factors of atherosclerosis (smoking and hypertension) were also evaluated. Our results indicate that the association of hypercholestolemia and hypertension is more dangerous than the co-occurence of hypercholesterolemia and smoking.     

Elective stenting of carotid artery stenosis in patients with severe coronary artery disease

AIMS: To evaluate the feasibility and safety of elective carotid stent implantation in patients with carotid stenoses and concomitant coronary artery disease, as an alternative to combined carotid and coronary surgery. METHODS: We treated 50 patients with >70%, stenoses in 53 carotid arteries with balloon angioplasty followed by elective stent implantation. All patients had severe coronary artery disease, and/or mitral insufficiency, aortic stenosis, rhythm disorders or generalized arteriosclerosis. In three patients the opposite carotid artery was occluded; nine patients had bilateral stenoses of which two received stents bilaterally. RESULTS: Fifty-six successful stent implantations (42 Wallstents, eight BeStents, two AVE-Microstents, one Palmaz Schatz stent, three Sito stents) were performed, reducing the baseline percent stenosis from 78 +/- 18%, to 13 +/- 11%. Complications included three transient ischaemic attacks, one minor and one major stroke. Follow-up was available for 46 patients over a mean of 10 months. Three asymptomatic restenoses and one deformation of a BeStent occurred. CONCLUSION: Our preliminary results indicate that carotid artery stenting in patients with concomitant severe coronary artery disease is feasible, safe, and may be an alternative to combined carotid and coronary surgery.     

Thrombogenic and atherogenic lipid modifications in plasma and patients with coronary artery disease and after coronary artery bypass surgery

BACKGROUND: Although multiple studies have shown that the left ventricular assist device (LVAD) improves distorted cardiac geometry, the pathological mechanisms of the "reverse remodeling" of the heart are unknown. Our goal was to determine the effects of LVAD support on cardiac myocyte size and shape. METHODS AND RESULTS: Isolated myocytes were obtained at cardiac transplantation from 30 failing hearts (12 ischemic, 18 nonischemic) without LVAD support, 10 failing hearts that received LVAD support for 75+/-15 days, and 6 nonfailing hearts. Cardiac myocyte volume, length, width, and thickness were determined by use of previously validated techniques. Isolated myocytes from myopathic hearts exhibited increased volume, length, width, and length-to-thickness ratio compared with normal myocytes (P<0.05). However, there were no differences in any parameter between myocytes from ischemic and nonischemic cardiomyopathic hearts. Long-term LVAD support resulted in a 28% reduction in myocyte volume, 20% reduction in cell length, 20% reduction in cell width, and 32% reduction in cell length-to-thickness ratio (P<0.05). In contrast, LVAD support was associated with no change in cell thickness. These cellular changes were associated with reductions in left ventricular dilation and left ventricular mass measured echocardiographically in 6 of 10 LVAD-supported patients. CONCLUSIONS: These studies suggest that the regression of cellular hypertrophy is a major contributor to the "reverse remodeling" of the heart after LVAD implantation. The favorable alterations in geometry that occur in parallel fashion at both the organ and cellular levels may contribute to reduced wall stress and improved mechanical performance after LVAD support.     

Insulin resistance in patients with familial combined hyperlipidemia and coronary artery disease

The minimum model modified by the administration of insulin provides an objective and relatively easily measured index of peripheral sensitivity to insulin which was significantly lower (p <0.02) in familial combined hyperlipidemia (FCH) with ischemic heart disease (IHD) than in FCH without IHD and in control subjects (1.2 +/- 0.6, 1.9 +/- 1.0, 2.9 +/- 1.2 x 10(-4) mU/L/ min, respectively). In patients with FCH, insulin resistance explains, at least in part, their metabolic alterations (hypertension, abnormal glucose tolerance, hyperinsulinemia) and elevated IHD.     

Myocardial glucose uptake in patients with NIDDM and stable coronary artery disease

Whole body insulin resistance characterizes patients with NIDDM, but it is not known whether insulin also has impaired ability to stimulate myocardial glucose uptake (MGU) in these patients. This study was designed to evaluate MGU as measured by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) in patients with NIDDM and stable coronary artery disease (CAD) under standardized metabolic conditions. Eight patients with NIDDM, 11 nondiabetic patients with CAD, and 9 healthy control subjects were enrolled in the study. MGU was quantitated in the normal myocardial regions with [18F]FDG and PET and the whole body glucose disposal by glucose-insulin clamp technique (serum insulin, -430 pmol/l). Plasma glucose and serum insulin concentrations were comparable in all groups during PET studies. The whole body glucose uptake was 45% lower in NIDDM patients (22 +/- 9 micromol x min(-1) X kg(-1) body wt [mean +/- SD]), compared with healthy control subjects (40 +/- 17 micromol x min(-1) x kg(-1) body wt, P < 0.05). In CAD patients, whole body glucose uptake was 30 +/- 9 micromol x min(-1) x kg(-1) body wt (NS between the other groups). MGU was similar in the normal segments in all three groups (69 +/- 28 micromol x min(-1) x 100 g(-1) in NIDDM patients, 72 +/- 17 micromol x min(-1) x 100 g(-1) in CAD patients, and 76 +/- 10 micromol x min(-1) x 100 g(-1) in healthy control subjects, NS). No correlation was found between whole body glucose uptake and MGU. As studied by [18F]FDG PET under stable normoglycemic hyperinsulinemic conditions, MGU is not reduced in patients with NIDDM and CAD in spite of peripheral insulin resistance. These findings suggest that there is no significant defect in MGU in patients with NIDDM.