Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

Diurnal fluctuations in human ventricular and atrial refractoriness.

The relative significance of the direct and indirect effects of autonomic tone on diurnal fluctuations in human ventricular and atrial refractoriness are not well known. In this study, the circadian rhythms of ventricular and atrial effective refractory periods (ERPs) were measured by noninvasive programmed stimulation in ten patients (mean age 62 +/- 10 years) who had a permanent dual chamber pacemaker for complete atrioventricular (AV) block. The ERP was measured at 4-hour intervals during spontaneous sinus rhythm with ventricular pacing (day 1) and during constant-rate dual chamber pacing (day 2). Cosinor analysis showed the ventricular ERP to have a significant diurnal rhythm in sinus rhythm (amplitude, 12 msec; 95% confidence intervals 1-24 msec) but not during constant-rate pacing (amplitude, 4 msec; 95% confidence intervals -3-12 msec). The atrial ERP had a significant rhythm at times of both spontaneous sinus rate (amplitude, 19 msec; confidence intervals 13-24 msec) and constant heart rate (amplitude, 11 msec; confidence intervals 1-21 msec) with acrophase during the sleeping hours. The increase in heart rate during dual chamber pacing resulted in a more marked decrease in the average 24-hour ERP in the ventricle than in the atrium (46 +/- 9 msec vs 12 +/- 6 msec, P < 0.01). Thus, refractoriness is more rate dependent in the ventricle than in the atrium, and autonomic influences on ventricular refractoriness are mainly indirect, via fluctuations in the sinus rate, but atrial refractoriness is also affected by direct neural influences and/or other rate independent factors.

Asymptomatic coronary artery disease in diabetes: relation to common risk factors, lipoproteins, apoproteins and apo E polymorphism.

The risk factors for asymptomatic coronary artery disease (CAD) were examined in 138 diabetic patients. Following non-invasive screening examinations (exercise electrocardiography, dynamic thallium scintigraphy, 24-h electrocardiographic recording), CAD was confirmed angiographically in 21 symptom-free diabetic subjects with an ischaemic finding in at least one of the non-invasive tests. The prevalence of asymptomatic CAD in this cohort of diabetic patients was 21/132 (16%), which may be an underestimation because 6 patients refused angiography. Risk factors (age, diabetes, smoking, hypertension, serum lipoproteins, apoproteins and apo E phenotypes) were analysed according to the presence or absence of CAD. Multivariate logistic stepwise analysis did not show any definite changes of serum lipids, lipoproteins and apoproteins in type 1 (n = 72) and type 2 (n = 66) diabetic patients with or without asymptomatic CAD. The only factors associated with asymptomatic CAD were the duration of diabetes (P < 0.005) and the age of the patient (P < 0.05). These results suggest that in diabetic patients the major risk factor for premature coronary atherosclerosis is diabetes itself. Assessment of other risk factors does not seem to define any subgroup with asymptomatic CAD.

Effect of preocclusion stenosis severity on heart rate reactions to coronary occlusion.

Autonomic mechanisms may have an important role in the clinical presentation of acute coronary occlusion. This research was designed to evaluate the effect of preocclusion stenosis severity on the immediate autonomic heart rate (HR) responses to a subsequent acute occlusion of the coronary artery. HR and its variability in the time and frequency domains were analyzed in patients with mild to moderate (< or = 85%) (group 1, n = 19) and severe (> 85%) (group 2, n = 18) left anterior descending coronary artery stenosis immediately before and during balloon occlusion (mean 108 seconds). The ranges of nonspecific responses were determined by analyzing HR reactions in a control group (n = 13) with no ischemia during balloon inflation of a totally occluded coronary artery. An abnormal increase in HR variability and/or bradycardia as a sign of vagal activation occurred in 6 patients (32%) in group 1 and in 3 patients (17%) in group 2. A significant decrease in HR variability or tachycardia, or both, was observed in 5 patients (26%) in group 1, but in none of the patients in group 2. Compared with the control group, the balloon occlusion of mild to moderate stenosis caused abnormal HR reactions more often than did occlusion of tight stenosis (58% vs 17%, p < 0.05). Balloon occlusions in group 1 caused chest pain (p < 0.01), ST-segment changes (p < 0.001), and narrowing of pulse pressure (p < 0.05) more often than did occlusions of severe stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of heart rate variability to coronary occlusion during coronary angioplasty.

Signs of sympathetic activation are frequent during the early hours of anterior wall acute myocardial infarction, whereas parasympathetic reflexes predominate in inferior wall acute myocardial infarction. To assess the immediate autonomic responses to acute coronary occlusion, the high-frequency power and root-mean-square successive difference, frequency and time domain measures of heart rate (HR) variability were analyzed in 73 cases of significant (50 to 95%) coronary artery stenosis immediately before and during balloon occlusion (mean 99 seconds). The range of nonspecific changes was formed on the basis of a control group with no ischemia during dilatations of 16 totally occluded coronary arteries. Balloon occlusion of the left anterior descending artery (n = 35) caused an abnormal increase in the measures of HR variability as a sign of vagal activation in 8 patients (23%), and a significant decrease in HR variability in 4 (11%). Occlusion of the left circumflex artery (n = 19) caused an increase in HR variability in 5 patients (26%), and a decrease in 2 (11%). Right coronary artery occlusion (n = 19) caused an increase in HR variability in 5 patients (26%) and a decrease in 4 (21%). Thus, coronary occlusion causes immediate changes in HR variability in greater than one third of patients with coronary artery disease. The direction of these initial HR variability changes cannot be predicted by the site of coronary occlusion.

Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen.

OBJECTIVE: Non-enzymatic glycosylation of proteins occurs in diabetes and advanced glycosylated end products can accumulate in long lived proteins such as vascular collagen and reduce the elasticity of vessel walls. To evaluate the potential association of advanced glycosylated end products in collagen with diminished arterial elasticity in diabetes, 14 diabetic and 14 age and sex matched non-diabetic patients with coronary artery disease were studied. METHODS: Arterial elasticity was assessed in terms of carotid to femoral pulse wave velocity and by measuring the change in ascending aortic diameter induced by pulse pressure. Collagen linked fluorescence, a measure of advanced glycosylated end products, was determined from tissue specimens of the skin, ascending aorta, and right atrial appendage taken during coronary bypass surgery. RESULTS: As a sign of diminished arterial elasticity, carotid to femoral pulse wave velocity was raised (p < 0.01) and change in ascending aortic diameter tended to be diminished (p = 0.09) in the diabetic patients. Collagen linked fluorescence was increased (p < 0.05) in the myocardium of the diabetic group, but the difference in skin and aorta was not significant. Collagen linked fluorescence between the aorta, skin, and myocardium correlated with each other (r = 0.64-0.77). Collagen linked fluorescence in the aorta and myocardium correlated with carotid to femoral pulse wave velocity (r = 0.63 and r = 0.67, respectively) in the diabetic group but not in the control group. CONCLUSIONS: These data suggest that non-enzymatic glycosylation of matrix proteins, and specifically collagen, may modify arterial elasticity in diabetic patients with coronary artery disease.

Release of atrial natriuretic peptide in relation to metabolic changes during myocardial ischaemia induced by coronary angioplasty.

The inter-relationships between ischaemia-induced metabolic changes and atrial natriuretic peptide (ANP) release were studied in 18 patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA). Transcardiac differences in ANP, lactate, pH, pCO2 and O2 saturation were analysed before and after balloon inflation. The patients were divided into ischaemia and non-ischaemia groups on the basis of the change in lactate extraction ratio during balloon inflation. The ischaemia group (patients with a decrease in lactate extraction ratio) showed an increase of 27 +/- 15 pg.ml-1 in the transcardiac ANP difference, whereas a decrease of 27 +/- 17 pg.ml-1 occurred in the non-ischaemia group (no decrease in lactate extraction ratio). The change between the two patient groups was statistically significant (P < 0.05). Metabolic 'pre-conditioning' was not observed in patients with successive dilatations, therefore data from all the dilatations were combined and evaluated by regression analysis. A correlation coefficient of 0.40 (P < 0.05) was obtained between the PTCA-induced changes in transcardiac ANP and lactate differences. We conclude that transient myocardial ischaemia induced by PTCA increases circulating ANP concentrations in patients with signs of metabolic ischaemia, but not in those without.

Changes in frequency domain measures of heart rate variability in relation to the onset of ventricular tachycardia in acute myocardial infarction.

The imbalance of the autonomic nervous function has been shown to contribute to the genesis of ventricular arrhythmias. Power spectral analysis of components of heart rate variability has the potential to quantify the cardiac autonomic tone during ambulatory electrocardiographic recording. We analysed the power spectral components of total power, very low frequency power (0.0033-0.04 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power in 12 consecutive patients accompanied with 27 episodes of ventricular tachycardia in acute myocardial infarction. The spectral areas were measured in 5-min periods preceding the onset of ventricular tachycardias. The total power of heart rate variability increased progressively before the onset of ventricular tachycardia episodes (P < 0.05). The increase of total power was mainly due to higher, very low frequency power at the onset rather than before the onset of ventricular tachycardia (P < 0.05). The trend towards adrenergic predominance at the onset of ventricular tachycardia was observed by an increase of average heart rate (P < 0.05) without concomitant increase in high frequency power. Thus, the occurrence of ventricular tachycardia is associated with changes in the power spectrum of heart rate variability suggesting alterations in autonomic tone at the onset of ventricular tachycardia in acute myocardial infarction.

Circadian rhythm of heart rate variability in survivors of cardiac arrest.

Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 +/- 10 vs 51 +/- 15 ms, p less than 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 +/- 7 ms2 x 10 vs 28 +/- 14 ms2 x 10, p less than 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest.

Efficacy and safety of anticoagulant therapy started pre-operatively in preventing coronary vein graft occlusion.

Oral anticoagulant therapy with warfarin commenced pre-operatively (n = 102) to prevent coronary artery vein graft occlusions was compared in terms of efficacy and safety with dipyridamole and aspirin (n = 130) in a randomized consecutive series of patients. Anticoagulant therapy was started at least 2 weeks before coronary artery bypass surgery (CABG) and antiplatelet therapy was started at least 3 days before CABG with dipyridamole followed by a combination of 250 mg aspirin once a day via a nasogastric tube 6 h after CABG. Overall, vein graft patency at 3 months after surgery did not differ significantly between the anticoagulant group (203/275, 74%) and dipyridamole-aspirin group (238/311, 77%), but the occlusion rate for grafts with endarterectomy was higher in the anticoagulant (46%) than in the dipyridamole and aspirin group (16%), (P less than 0.05). The rate of peri-operative complications including deaths, re-operation and myocardial infarction was higher in the anticoagulant than antiplatelet group (26.5% vs 13.8%, P less than 0.05). The occurrence of postoperative bleeding complications did not differ significantly between the groups. Thus, oral anticoagulant therapy commenced pre-operatively has no advantages over conventional antiplatelet therapy in patients who undergo CABG. Neither antithrombotic regimens proved to be satisfactory for preventing acute bypass vein graft occlusions in this patient population with advanced coronary artery disease.

Usefulness of a postoperative exercise test for predicting cardiac events after coronary artery bypass grafting.

The predictive value of a postoperative exercise test in terms of cardiac events after coronary artery bypass grafting (CABG) was prospectively studied in 231 consecutive patients. During a 5-year follow-up there were 28 cardiac events (12%), of which 15 were cardiac deaths (13 sudden), and 13 were nonfatal myocardial infarctions. There was no difference in the rate of graft patency between groups with and without cardiac events, but ejection fraction was lower in patients with than without events (51 +/- 16% vs 58 +/- 10%; p less than 0.05). Duration of the exercise test was shorter, and maximal work load was lower in patients with cardiac events (p less than 0.05 for both). The prevalence of greater than or equal to 1 mm ST-segment depression was 22% (symptomatic in 25%, and silent in 75%) and did not differ between groups with and without cardiac events. After adjustment for prognostic variables using the proportional hazards method, diuretic treatment (p = 0.007) and a low postoperative ejection fraction (p = 0.04) remained significant for predicting the risk of cardiac events within 5 years of CABG, but exercise duration and work load did not have any significant predictive value. Thus, the predictive value of a postoperative exercise test is limited, and signs of impaired left ventricular function are of greater significance for the 5-year prognosis after CABG than are those of myocardial ischemia.

Effect of coronary artery bypass grafting on cardiac parasympathetic nervous function.

Low heart rate variability (HRV) is a predictor of a poor outcome after myocardial infarction. To determine whether coronary artery bypass grafting (CABG) has any effect on HRV, the power spectrum components of HRV were measured in 35 patients before, and 1 week after, CABG. Significant attenuation of all spectral components of HRV were found after CABG (P less than 0.001). High frequency (HF) power decreased to one third of the preoperative level, mid-frequency (MF) power to as little as one fifteenth and low frequency (LF) power to one seventh of the preoperative level. No significant restoration in MF or HF powers occurred during the 6-week follow-up period. The results suggest that CABG causes a marked attenuation of HRV. The prognostic significance of this attenuation is not known.

Clinical and angiographic prediction of cardiac death after coronary artery bypass graft surgery.

OBJECTIVES: To study the risk factors for cardiac mortality after coronary artery bypass graft surgery. DESIGN AND SETTING: Follow up study of patients who had undergone coronary artery bypass graft surgery at the University Hospital of Oulu, Finland. PATIENTS AND INTERVENTIONS: 339 consecutive patients who underwent cardiac catheterisation three months after bypass surgery. MAIN OUTCOME MEASURES: Incidence of cardiac deaths during the follow up period of five years and predictive value of clinical and angiographic variables for subsequent cardiac mortality. RESULTS: The incidence of cardiac deaths was 5.1%, and 81% of these were sudden deaths. The postoperative ejection fraction was significantly lower in the patients with subsequent cardiac death than in the survivors (p less than 0.001), and their left ventricular end systolic and end diastolic volumes were higher (p less than 0.001 and p less than 0.05 respectively). The incidence of cardiac deaths was 43% in the patients with a postoperative ejection fraction of less than 40%. The myocardial jeopardy index after surgery and the rate of graft patency were not significantly different in the survivors and patients who died. The only clinical factors that were different between the groups were postoperative use of diuretics (p less than 0.001) or digitalis (p = 0.02). After adjustment for other prognostic variables by the proportional hazards method, a low postoperative ejection fraction remained significant as a predictor of the relative risk of cardiac mortality five years after operation (p less than 0.01). CONCLUSIONS: Patients with angiographic evidence of impaired left ventricular function after bypass surgery are still at relatively high risk of dying suddenly, but myocardial ischaemia due to incomplete revascularisation is not strongly associated with an increased risk of cardiac mortality. Conventional clinical methods do not seem to be helpful for identifying patients with an increased risk of cardiac death after bypass surgery.

Circadian variation of ventricular tachycardia in patients with coronary arterial disease.

Sudden cardiac death and ischaemic cardiac events occur in a circadian pattern. Because ventricular tachycardia is thought to play an important role in sudden cardiac death, the episodes of spontaneous ventricular tachycardias (greater than 3 consecutive beats) (n = 1314) were analysed from 24-hour long term electrocardiographic recordings in 34 patients with coronary arterial disease to determine whether circadian rhythm exists in spontaneous ventricular tachycardia. Twelve patients had suffered cardiac arrest, four patients had a history of syncope, and palpitation was the indication for electrocardiographic recordings in eighteen patients. Analysis using chronobiologic single cosinor method showed a significant circadian variation in the occurrence of ventricular tachycardia episodes with the peak occurring at 6 a.m. Similar circadian rhythm was also observed in the occurrence of the longest episode of ventricular tachycardia. Ischaemic ST-segment depression preceded the longest ventricular tachycardia episode only in one patient. Thus, a circadian rhythm occurs also in spontaneous episodes of ventricular tachycardia, a finding which is similar to that in sudden cardiac death.

Asymptomatic coronary artery disease in diabetes: associated with autonomic neuropathy?

To elucidate the potential association of diabetic autonomic neuropathy with increased prevalence of silent coronary artery disease (CAD), 138 asymptomatic diabetic subjects were screened using exercise ECG. 24-h ambulatory ECG and dynamic thallium scintigraphy. Fourteen patients with exercise-induced myocardial ischaemia and angiographically confirmed CAD (greater than or equal to 50% coronary artery narrowing) were found using this protocol. Their autonomic nervous function was assessed using standard cardiovascular tests and compared with that of 23 consecutive diabetic patients catheterised because of symptomatic CAD (mean New York Heart Association class 3.0). The diabetic patients with symptomatic CAD had more severe coronary atherosclerosis than the diabetic patients with asymptomatic CAD assessed by jeopardy score (P less than 0.01). The groups did not, however, differ with respect to autonomic function tests. Five patients (22%) with symptomatic CAD and 3 patients (21%) with asymptomatic CAD had definite autonomic dysfunction, i.e. two or more abnormal tests. Thus, our results suggest that the frequency of autonomic neuropathy is not increased in diabetic patients with asymptomatic CAD. The contribution of diabetic autonomic neuropathy to the absence of cardiac pain needs further clinical and pathological studies.

Effect of coronary arterial occlusion on vagal control of heart rate.

Diminished variation in heart rate as a sign of impaired vagal control is common in coronary arterial disease. To evaluate the effect of short-term myocardial ischaemia induced by coronary arterial occlusion during therapeutic percutaneous transluminal coronary angioplasty we measured the variation in heart rate during controlled deep breathing in 50 patients before and during arterial occlusion. Variation in heart rate diminished from 11.1 +/- 4.5 to 9.5 +/- 5.1 beats/min (P less than 0.01) during occlusion. No change occurred in heart rate, blood pressure or levels of noradrenaline and adrenaline. The attenuation of variation in the heart rate was not significantly associated with the site or duration of arterial occlusion nor concomitant chest pain. Thus, brief coronary arterial occlusion seems to be associated with impairment of the vagal control of heart rate in patients with coronary arterial disease.

Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting.

Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise-induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/- 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death.

Autonomic influence on pregnancy outcome in IDDM.

We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy.

Prevalence and prognostic significance of complex ventricular arrhythmias after coronary arterial bypass graft surgery.

To assess the prevalence and long-term prognostic significance of complex ventricular arrhythmias after coronary arterial bypass graft surgery, 126 patients were studied by 24-hour ambulatory electrocardiographic recordings and cardiac catheterizations (including left ventricular, coronary arterial and bypass graft angiograms) before and 3 months after surgery, and then prospectively followed-up for a mean of 50 months. Complex ventricular arrhythmias (ventricular premature complexes greater than 30/hour, multiform and/or repetitive complexes) occurred more commonly after than before surgery (in 49/126 vs. 30/126 patients, P less than 0.05). In 18 patients (14%) who had significant worsening of ventricular arrhythmias, the ejection fraction decreased significantly (from 56 +/- 13% to 50 +/- 15%, P less than 0.05) after operation. During the period of follow-up, there were 4 witnessed sudden cardiac deaths. Complex ventricular arrhythmias tended to be more prevalent in patients who died suddenly (in 100%) compared to survivors (in 37%), but their presence did not predict the subsequent sudden death when ejection fraction was included in the stepwise regression model. None of the patients with an ejection fraction over 40% suffered sudden death despite the prevalence of complex arrhythmias in 32% of these patients. Thus, complex ventricular arrhythmias tend to occur more frequently after than before bypass surgery and their occurrence appears to be related to impairment of left ventricular function. Patients with well preserved ventricular function are at low risk of dying suddenly despite presence of complex ventricular arrhythmias after surgery.