Association of risk factor variables and coronary artery disease documented with angiography

Stepwise linear discrimination was used to analyze risk factors in 431 consecutive patients who underwent coronary angiography to determine which variables were most closely associated with coronary artery disease. Twenty-one risk factors were considered: total plasma cholesterol and triglycerides; the cholesterol and triglyceride content of high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low density lipoproteins (VLDL); and the percentage of total cholesterol and triglycerides in each fraction. Age, smoking history, family history, hypertension, diabetes mellitus and relative weight were also considered. Coronary artery disease was assessed using three standard grading scores. There were significant differences in risk factors between males and females. In males, LDL cholesterol and age were selected by multivariate analysis. In females, the ratio of HDL cholesterol to total cholesterol, as well as relative weight, family history, age and smoking were selected. The discriminating value of HDL cholesterol as the percentage of total cholesterol was significantly greater than that of HDL cholesterol itself. Despite highly significant associations between risk factors and the presence of coronary artery disease, the discrimination did not provide sufficient separation of the groups to give results that are useful diagnostically in individual patients.     

Circulatory changes in patients with coronary artery disease following thiamylal-succinylcholine and tracheal intubation

After introductory remarks concerning the Posner-Schlossman-syndrome (syndrome of glaucomatocyclitic crises) a case is reviewed. The concurrence with Addison's disease in this patient gives rise to speculations as to possible connections between the two conditions, but the conclusion is that the simultaneous occurrence of the two diseases at present must be regarded as coincidental.     

Plasma insulin levels in coronary artery disease

Seventy two consecutive patients without a history of diabetes and normal fasting plasma glucose were included in this study of insulin levels. Standard oral glucose tolerance test with 75 gm glucose and fasting and two hour insulin levels were estimated in all patients. Coronary artery disease (CAD) was confirmed or excluded by selective coronary arteriography. In 20 patients, CAD was diagnosed by electrocardiographic (ECG) and clinical evidence of earlier myocardial infarction. Mean fasting plasma insulin was 31.40 +/- 22.2 IU/dl in the CAD positive and 32.3 +/- 13.6 IU/dl in the CAD negative group. The mean two hour plasma insulin was 274.6 +/- 301.1 IU/dl in the CAD positive and 104.8 +/- 74.9 IU/dl in the CAD negative group (p < 0.04). Two hour plasma insulin levels were significantly higher in patients with atherosclerotic coronary artery disease. It is concluded that the estimation of a two hour plasma insulin level after 75 gm of glucose load, could help differentiate CAD from normals.     

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.     

Contents of trans-fatty acids in human substernal adipose tissue and plasma lipids: relation to angiographically documented coronary heart disease

The contents of trans-fatty acid (TFA) isomers of human substernal adipose tissue and plasma lipids (cholesterol esters, triacylglycerols, phospholipids), obtained from patients with angiographically documented coronary heart disease (CHD group; n = 24) and from controls (excluded CHD; n = 25), were determined by capillary gas chromatography. No significant difference (P <0.05) could be observed between cases (2.59 +/- 33%) and controls (2.79 +/- 0.76%) with regard to adipose tissue total TFA contents (expressed as proportion of all identified fatty acid methyl esters). The total adipose tissue TFA content reflected the dietary TFA intake, which was estimated by dietary questionnaires. Both groups showed significant differences in several isomeric plasma lipid TFA. Cases generally had a tendency to lower individual TFA contents.     

Changes in coronary vasodilation in hypertensive patients with angiographically normal coronary arteries

In normal subjects, coronary arteries dilate in response to sympathetic stimulation evoked by the cold pressor test. Similarly, in normal coronary arteries the increase in blood flow velocity induced by papaverine results in flow-dependent coronary dilation. In order to assess the coronary responses to both stimuli in hypertensive patients, variations of proximal left anterior descending coronary artery diameters and coronary blood flow velocity have been measured using quantitative coronary angiography and intracoronary Doppler in 10 control subjects and in 12 hypertensive patients. All the patients had angiographically normal coronary arteries. Total serum cholesterol, triglycerides, HDL- and LDL-cholesterol were within normal range in all patients. All patients were nonsmokers and none of them had diabetes mellitus. During the cold pressor test (hands immersed in ice water for 120 s), the rate-pressure product and coronary blood flow velocity increased respectively by 33 +/- 9% (p < 0.001) and 51 +/- 26% (p < 0.05) in control subjects, by 28 +/- 18% (p < 0.001) and 68 +/- 52% (p < 0.05) in hypertensive patients. In control subjects, coronary arteries dilated by + 12.0 +/- 4.4% (p < 0.001), and constricted by -10.3 +/- 8.5% (p < 0.001) in hypertensive patients. After injection of 10 mg of papaverine into the distal left anterior descending coronary artery, proximal left anterior descending coronary artery dilated by + 17.0 +/- 10.6% (p < 0.001) in control subjects, and did not vary (-0.7% +/- 10.6%) in hypertensive patients, when blood flow velocity was increased respectively by 449 +/- 97% and 383 +/- 103% (p < 0.001 in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiographically documented coronary artery disease in asymptomatic middle aged men suspected of silent ischaemic heart disease

One hundred and fourteen asymptomatic middle aged men, with a positive stress test, underwent coronary angiography at Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC/NIHD), Rawalpindi. Of these, 66 (58%) were found to have significant disease (> 50% luminal narrowing in at least one of the major epicardial arteries) while 48 (42%) had normal coronary arteries. Of the former, 27 (41%) had 1-vessel CAD, 18 (27%) had 2-vessel CAD and 21 (32%) had 3-vessel CAD. There were significantly more hypertensives, hyperlipidaemics and diabetics in CAD group, while other risk factors were the same. The overall risk factor prevalence was low. The major reasons for performing coronary angiography were a positive stress test done as part of routine annual medical checkup and resting ECG changes of enough significance to warrant further investigations. It is concluded that the presence of significant coronary artery disease can be silent in a large number of asymptomatic middle aged men, especially those who have conventional risk factors.     

Reversal of somatostatin inhibition of insulin and glucagon secretion

These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.5 mM as stimulus primarily for IRG but also IRI secretion. The effects of excess Ca++ (15.2 mEq./L.) and excess K+ (12.8 mEq./L.) on IRG, IRI, and the SRIF-inhibited pancreas were studied. Ca++ excess in five perfusions strikingly stimulated IRG secretion (+92 per cent) but only stabilized IRI secretion compared with control perfusions. K+ excess (in seven perfusions) markedly inhibited IRG secretion (-39 per cent) while stimulating IRI secretion (+16 per cent). Restoration of normal concentrations of K+ resulted in a rebound of IRG to levels 120 per cent that of controls. SRIF, at concentrations from 0.1-20 ng./ml., produced inhibition of both IRG and IRI. In 11 perfusions, with SRIF at 10 ng./ml., IRG decreased more than IRI (-75.2 per cent IRG and -46.9 per cent IRI). In five perfusions, addition of Ca++ (15.2 mEq./L.) 10 minutes after SRIF was started resulted in a reversal of IRG inhibition to 69.4 per cent and IRI to 73.2 per cent of the arginine controls. The reversal by Ca++ of SRIF effect on IRG was greater at higher concentrations of Ca++, suggesting some form of competition. In four perfusions, excess K+ reversed SRIF-induced IRI inhibition to 79.6 per cent that of controls but had no effect on IRG inhibition. Studies in vitro with isolated islets revealed that SRIF (2 mug./ml.) inhibited 45Ca uptake of islets as did epinephrine (10(-5) M). It was concluded that SRIF-induced inhibition of hormone release appears related to an action on Ca++ uptake.     

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.     

'True' fasting serum insulin level, insulin resistance syndrome and coronary artery disease

BACKGROUND: Increased fasting serum insulin level not associated with hypoglycemia is considered to be a practical indicator of the insulin resistance syndrome, a frequent risk factor for atherosclerosis in industrialized countries. However, in most studies, insulin was measured by using antibodies which cross-react with proinsulin and 31/32, 32/33 split products of insulin. We re-examined the correlations between the insulin resistance syndrome and 'true' fasting serum insulin level. METHODS: We studied 242 post-menopausal women (age 63 +/- 8 years), a population in whom insulin resistance syndrome is particularly frequent. Serum insulin was measured by a recent specific microparticle immunoassay. RESULTS: There was a significant correlation between elevated 'true' fasting serum insulin level and various constituents of the insulin resistance syndrome, such as obesity, dyslipidemia (hypertriglyceridemia, increased apolipoprotein B and decreased high-density lipoprotein cholesterol and apolipoprotein A1 concentrations), increased serum glucose, uric acid levels, and plasminogen activator inhibitor type I concentration, as well as increased frequency of diabetes. There was also a correlation between insulin level and various manifestations of coronary artery disease: patients in the highest quartile of 'true' insulin level had significantly more entirely occluded coronary arteries than in the lowest one. Similarly, in the highest insulin quartile more patients had occluded arteries with lumen diameter stenoses greater than 50% (P < 0.05) and more of them had history of previous myocardial infarction approaching the level of significance (P = 0.0587) than in the lowest one. Most of these correlations were also noted in nondiabetic people. CONCLUSIONS: An increase of 'true' fasting serum insulin level is a useful practical index to identify patients with the insulin resistance syndrome exposed to increased risk of coronary artery disease.     

Arginine-stimulated acute phase of insulin and glucagon secretion in diabetic subjects

To determine if both phases of glucagon secretion are excessive in diabetes, arginine was admimistered intravenously as pulses and as infusions to normal subjects, insulin-dependent diabetics, and noninsulin-requiring diabetics. The acute phase of glucagon secretion, in response to arginine pulses at four different doses (submaximal to maximal alpha-cell stimulating), was indistinguishable in terms of timing, peak levels attained, and total increments comparing controls and diabetics. During the first half of the arginine infusion (500 mg/kg over 30 min) the glucagon rise in controls and diabetics was similar (P greater than 0.1), whereas during the last half of the infusion excessive glucagon levels were seen in the diabetics. No difference in the glucagon responses to arginine administered as either a pulse or an infusion was observed between the two types of diabetics. The acute phase responses of insulin to intravenous, maximal stimulating doses of glucose (20 g) and arginine (2.5 g) were measured in five insulin-independent diabetics. Although the acute insulin response to arginine was normal, there was marked attentuation of the early beta-cell response upon stimulation by glucose. From these results we conclude that although in diabetes excessive glucagon levels are observed with chronic arginine stimulation, the acute phase of glucagon secretion in response to arginine is normal. In addition, the beta-cell in noninsulin-requiring diabetics, although acutely hyporesponsive to glucose, remains normally responsive to another stimulus, arginine.     

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.     

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.     

Effect of pravastatin (10 mg/day) on progression of coronary atherosclerosis in patients with serum total cholesterol levels from 160 to 220 mg/dl and angiographically documented coronary artery disease. Coronary Artery Regression Study (CARS) Group

To evaluate the effect of pravastatin on progression of coronary atherosclerosis in normocholesterolemic patients with coronary artery disease (CAD), 90 patients with CAD and serum cholesterol levels of 160 to 220 mg/dl were randomized into a pravastatin (10 mg/day) group (n = 45) and control group (n = 45) in a 2-year study. The proportions of patients with progression (an increase of > or = 15% in percent stenosis) and regression (a decrease of > or = 15% in percent stenosis) of coronary atherosclerosis were compared between the 2 groups. Of 90 patients, 80 (89%) had a final angiogram: the pravastatin (n = 39) and control group (n = 41). Percent changes in total cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels were significantly greater in the pravastatin group than in the control group (total cholesterol -11 +/- 12% vs 3 +/- 15%, p < 0.01; low-density lipoprotein cholesterol -18 +/- 16% vs 4 +/- 21%, p < 0.01; apoprotein B -5 +/- 20% vs 6 +/- 20%, p < 0.05). The proportion of patients with progression of coronary atherosclerosis was significantly smaller in the pravastatin group than in the control group (21% vs 49%, p < 0.05). The proportion of patients with disease regression did not differ in the 2 groups (3% vs 2%, p = NS). In conclusion, this study indicates that cholesterol-lowering therapy with pravastatin can prevent the progression of coronary atherosclerosis even in normocholesterolemic patients with established CAD.     

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.     

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.