Free cholesterol concentrations in the high-density lipoprotein subfraction-3 as a risk indicator in patients with angiographically documented coronary artery disease.

BACKGROUND: The pathophysiology of plasma lipoprotein metabolism has long been linked to coronary artery disease (CAD). The present study evaluated the association between plasma lipoprotein lipid and apolipoprotein (apo) components and CAD in a group of 80 consecutive Caucasian patients undergoing coronary angiography. METHODS: Coronary cineangiography was carried out using the Judkins technique and the lesions quantified by calculating a coronary artery lesion score (CALS). Very low- and low-density lipoproteins (VLDL and LDL) were separated by ultracentrifugation, and high-density lipoprotein (HDL) and HDL subfraction-3 (HDL3) isolated by a differential precipitation procedure. Apo A-I, A-II, and B were assayed by endpoint laser nephelometry using specific antibodies. Total cholesterol, free cholesterol, and fatty acid concentrations were measured by gas-liquid chromatography, and lecithin: cholesterol acyltransferase (LCAT) activity by the decrease in the concentration of free cholesterol. RESULTS: On the basis of the presence of CAD, the 80 patients were divided into two groups: 52 (65%) with CAD (mean CALS = 7.8) and 28 (35%) without CAD (zero CALS). The lipoprotein fraction that most clearly differentiated the groups was HDL cholesterol concentration, with a mean +/- SEM value of 36.5 +/- 1.5 mg/dl for those with CAD and 45.1 +/- 2.1 mg/dl for those without (P < 0.01). The mean HDL3 cholesterol concentration was 29.9 +/- 1.2 mg/dl for patients with CAD and 37.4 +/- 1.8 mg/dl for those without (P < 0.001). These differences in HDL cholesterol and HDL3 cholesterol were mainly caused by differences in the free cholesterol component, with a mean HDL free cholesterol level of 10.8 +/- 1.1 and 16.1 +/- 1.4 mg/dl (P < 0.01), and a mean HDL3 free cholesterol level of 7.6 +/- 0.6 and 11.9 +/- 0.8 mg/dl (P < 0.001) in patients with and without CAD, respectively. Plasma LCAT activity was decreased in patients with CAD (P < 0.05), as were the apo A-I and A-II concentrations in both the HDL (P < 0.001) and HDL3 (P < 0.001) fractions. No significant association was found between CAD and HDL2 cholesterol or plasma total cholesterol, LDL cholesterol, or VLDL cholesterol concentrations. A stepwise discriminant analysis revealed that HDL3 free cholesterol was the only variable selected. Using HDL3 free cholesterol as a screening variable for CAD (cutoff 10.55 mg/dl), the sensitivity for CAD was 87% and the specificity for non-CAD 67%. The positive and negative predictive values of HDL3 free cholesterol were 82 and 75%, respectively. CONCLUSION: We have shown that the concentrations of HDL cholesterol and HDL3 most clearly differentiated between patients with and without CAD.

Acute coronary thrombus formation after stress testing following percutaneous transluminal coronary angioplasty. A case report.

Successful percutaneous transluminal coronary angioplasty (PTCA) was performed on a 37-year-old white man with an isolated 95% right coronary artery stenosis who initially presented with type II unstable angina. Submaximal treadmill stress testing was not carried out before PTCA, but testing 3 days after PTCA was strongly positive without accompanying symptoms of myocardial ischaemia. Some 30 minutes after this test the patient experienced severe precordial pain with features of a hyperacute transmural inferior myocardial infarction. Immediate coronary arteriography delineated fresh thrombus related to the previous PTCA site. Intracoronary thrombolysis with streptokinase was successful, revealing an underlying severe stenosis at the PTCA site. PTCA was not repeated, nor was emergency coronary artery bypass grafting (CABG) performed. This is the second such case documented in the literature; the first patient failed to respond to intracoronary thrombolysis with streptokinase and was submitted to emergency CABG. The possible underlying pathophysiological mechanisms are discussed. We believe that the late thrombus formation was directly related to submaximal stress testing after successful PTCA, and recommend that testing to assess the efficacy of PTCA be deferred until at least 1 month after the procedure to allow for completion of the healing process.

Late symptomatic exercise-induced coronary vasospasm after percutaneous transluminal coronary angioplasty. A case report and review.

A patient who underwent a successful double-vessel percutaneous transluminal coronary angioplasty (PTCA) had suffered from exercise-induced ST-segment elevation associated with angina pectoris (AP). This ECG pattern was present both before and 12 months after PTCA while nifedipine (Adalat; Bayer-Miles) therapy was electively discontinued. Reintroduction of calcium blockade with this drug eliminated the chest pain and resulted in normalization of the stress ECG. Cardiac catheterization at 6 and 12 months after PTCA demonstrated continuing angiographic improvement of the coronary stenoses of the left anterior descending and left circumflex (LCx) coronary arteries previously subjected to PTCA. It is believed that coronary artery spasm at the PTCA site on the LCx coronary artery was responsible for the AP and exercise-induced ST-segment elevation. Likely pathogenetic mechanisms of coronary vasospasm during and after the performance of PTCA, as well as the interrelationship with re-stenosis and the clinical implications of drug therapy, are discussed.

The extraction of thallium-201 by the myocardium.

The concentration of thallium-201 in the myocardium immediately following injection of tracer is the result of both blood flow delivering tracer to the heart and extraction by the myocardium. In these studies, the extraction of thallium-201 by the canine myocardium was determined as a function of heart rate, coronary blood flow, hypoxia, changes in pH, and following administration of propranolol, insulin, and strophanthin. Under basal conditions, extraction fraction measured 88 +/- 2.1%, following pacing to a rate of 195 beats/min extraction fraction remained unchanged at 88.5%. Similar results were found with changes in pH, propranolol, insulin, and strophanthin. Hypoxia caused a significant decrease in extraction fraction to 77.9%. When coronary blood flow was increased in excess of demands by drugs, extraction fraction fell logarithmically.

Pre-operative assessment of cardiac patients for non-cardiac surgery.

Non-cardiac surgery presents significant risks to patients with cardiac diseases. With the improvement in anaesthetic techniques and intensive care facilities, many cardiac patients who in the past would have been considered as being at too great a risk are now being considered for non-cardiac surgery. Smaller centres must still practise strict selection of patients if they do not possess an intensive care unit with facilities for full haemodynamic monitoring. We present a review of the recent literature and current practice at our hospital to assist clinicians in assessing these patients for anaesthesia. However, the final decision whether the patient is fit for anaesthesia still rests with the anaesthetist.

[Primary echinococcus cyst of the heart. A case report]. / Primêre echinococcus-sist van die hart. N gevalbespreking.

A young male commercial pilot, completely asymptomatic of heart disease, was found to have an abnormal ECG on routine examination. This consisted of a bifascicular block (left anterior hemiblock plus a complete right bundle-branch block). Aviation regulations demanded further examination to rule out possible cardiac disease. On two occasions in 1984 and again in 1986 cardiac catheterisation was performed and revealed normal left ventricular function and normal coronary arteries. On 15 April 1986 an echocardiogram revealed a large cystic mass in the right ventricle, which was further delineated by right-sided cine-angiography. The patient was referred for cardiac surgery with the diagnosis of an Echinococcus cyst as the most likely possibility. Open-heart surgery was performed on 16 July 1986 and a 4 x 4 cm hydatid cyst, originating from the right ventricle septum and projecting into the right ventricular cavity, was removed. The diagnosis of Echinococcus granulosus was confirmed by histological examination.

A comparison of the metabolic effects of captopril and atenolol on glucose, insulin and lipoproteins in patients with mild-to-moderate essential hypertension.

The metabolic effects of captopril 25 mg twice daily and atenolol 50 mg daily on glucose, insulin and lipids were compared in 83 otherwise healthy mild-to-moderate hypertensive between the ages of 25 and 60 years in a randomised double-blind trial. Hourly glucose and insulin levels were measured during a 2-hour 75 g oral glucose tolerance test at baseline and after 12 weeks of treatment. Lipid profiles including total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2, HDL3, triglycerides, apoprotein (Apo)A1, ApoB, and Apo(a) were obtained before and after the treatment period. Blood pressure decreased significantly and equivalently in both treatment groups. The glucose and insulin levels and glucose x insulin product at 2 hours after the glucose load increased after 12 weeks of treatment with atenolol compared with the baseline values, but these parameters all decreased after the treatment period with captopril compared with their baseline values. These results indicate an improvement in insulin sensitivity with captopril and a deterioration with atenolol. HDL-cholesterol and HDL3 decreased in the atenolol group but increased in the captopril group. We conclude that captopril has more favourable effects than atenolol on glucose, insulin and lipid metabolism in the treatment of mild-to-moderate hypertension.

[The correlation between ECG characteristics and hemodynamic results in isolated atrial septal defects]. / Die korrelasie tussen EKG-eienskappe en hemodinamiese gevolge van geïsoleerde atriale septale defekte.

Electrocardiographic characteristics and haemodynamic findings in 30 patients with secundum atrial septal defects were correlated retrospectively to determine whether any haemodynamic deductions could be made based on ECG findings. Although statistically significant correlations were found, no accurate haemodynamic estimations could be made based on ECG findings.

The prevalence of ischaemic heart disease in three rural South African communities.

In a population reportedly excessively prone to ischaemic heart disease (IHD) i.e. South African (SA) whites, a 3-community study of 7188 subjects aged 15-64 showed a high prevalence of chest pain by questionnaire (9.5% of males, 7.7% of females) or by ECG findings suggestive of IHD (12.8% males, 6.7% females). In the oldest decile (55-64 years) the prevalence of chest pain and/or ECG findings was 33.4% of males and 26.1% of females. For all ages, 18.4% of males and 13.1% of females were apparently affected. Though females were as likely as males to have a history of chest pain they had fewer ECG findings suggestive of IHD and the history was less likely to have been confirmed by a doctor. The significance of individual findings, assessed by the strength of their associations with symptomatic history and age, appeared to differ between the sexes; though very common, medium S-T depression was not classed as suggestive of IHD in females, while left ventricular hypertrophy was unimpressive in males. Large and medium Q waves, large S-T depression, large and medium T wave inversion were positive in both sexes, but left and right bundle branch block only in males. There was little overlap between a history of chest pain and suggestive ECG findings; however, a previous diagnosis of IHD by the family doctor increased the overlap by up to 6 times.

Electron microscopic analysis of the specific granule content of human atria. An investigation of the role of atrial pressure and atrial rhythm in the release of atrial natriuretic peptide.

Knowledge about the stimulus for the release of atrial natriuretic peptide (ANP) from human atria is incomplete. Atrial stretch is known to be a stimulus and atrial tachyarrhythmias are thought to be another. The effects of atrial size (by two-dimensional echocardiography) and atrial fibrillation on the atrial specific granule content of human atria were studied to gain insight into the secretory mechanisms of ANP. An electron microscopic analysis of the atrial granule content was used to study 12 patients--5 with mitral stenosis and sinus rhythm, 3 with mitral stenosis and atrial fibrillation and 4 controls. Granules were counted using a free count and montage method. This is the first report of such a morphometric analysis in humans. Granule counts were significantly raised in the patients with mitral stenosis compared with controls (P less than 0.014). This observation probably reflects a high turnover state induced by elevated atrial pressures. Further support for this conclusion is provided by the demonstration of a positive correlation between granule counts and left atrial size (r = 0.86; P less than 0.01). The tendency for higher counts in patients with atrial fibrillation may be related to the rhythm disturbance itself, but clinical and echocardiographic data suggest more severe atrial pressure overload in this group.

[Aortocoronary bypass surgery at Tygerberg Hospital, 1978 - 1980]. / Aortokoronêre omleidingschirurgie te Tygerberg-hospitaal, 1978-1980.

Between January 1978 and December 1980. 118 patients underwent saphenous vein bypass surgery for obstructive coronary artery disease at Tygerberg Hospital. Sixteen patients in addition to bypass surgery underwent mitral and/or aortic valve replacement or resection of a ventricular aneurysm. The operative and hospital mortality was 3,0% (4/134) for all patients and 3,3% (4/118) for patients who had aortocoronary bypass surgery as the sole procedure. Follow-up of the surviving patients for a mean period of 16,4 months revealed a low incidence of late myocardial infarction of 3.6% (4/112) resulting in the death of only 1 patient; 89.1% of patients were free of angina pectoris and the majority of these resumed their normal work or enjoyed their retirement.

A DNA polymorphism in the human low-density lipoprotein receptor gene.

A new restriction fragment length polymorphism (RFLP) in the low-density lipoprotein receptor gene is described using the Stu I restriction endonuclease and a cDNA probe. The frequency of the two RFLP alleles was determined in 60 unrelated white subjects and 11.7% of them were found to be heterozygous for the polymorphism. Mendelian segregation of the RFLP was found in 3 informative families. The possible use of the RFLP in the diagnosis of familial hypercholesterolaemia in South Africa is discussed.

[The effect of heparin induced increase of free plasma thyroxine on cardiac rhythm after myocardial infarction]. / Die effek van heparien-geïnduseerde styging in vrye plasmatiroksien op die hartritme na miokardiale infarksie.

It is well known that an acute myocardial infarction is accompanied by a rise in levels of plasma free fatty acids (FFA), which may lead to a subsequent increase in cardiac arrhythmias. Administration of heparin to patients after an acute myocardial infarction gives rise to an increase both in plasma FFA levels and plasma free thyroxine levels. If administered without a fatty meal the rise in FFA is not accompanied by an increase in arrhythmias. The effect of the heparin-induced rise in plasma free thyroxine on cardiac rhythm has never been investigated. The aim of the present study was to investigate a possible arrhythmic effect of a heparin induced increase in plasma free thyroxine in a group of patients with acute myocardial infarction. We were able to confirm a significant heparin-induced rise in plasma free thyroxine levels, as measured by the effective thyroxine ratio. Although a slightly significant increase in ventricular premature beats could be demonstrated after heparin administration when using the Wilcoxon rank sum test for statistical analysis (but not when the paired t-test was utilized), no significant correlation with free thyroxine levels could be found. Heparin administration to patients suffering from myocardial infarction seems to be safe in terms of a possible arrhythmic effect.

Effects of nifedipine on the peri-operative ECG, as determined by continuous Holter monitoring. A double-blind study.

A double-blind study was performed on 50 elderly patients undergoing hip-replacement surgery under general anaesthesia; 26 were given nifedipine and the remaining 24 placebo to determine effects on the continuously monitored (Holter) ECG during the 4 peri-operative days. Drugs were only administered during the latter 3 days of the observation period. Surgery was performed on the morning of the 3rd day. A striking feature was the high incidence of arrhythmias in both groups of patients, a finding previously documented in both 'normal' and elderly people. A decrease in ST-segment changes was expected in the nifedipine-treated patients. An unexpected finding, therefore, was the lack of protection against cardiac ischaemic changes in the nifedipine-treated patients compared with the placebo patients. Interpretation of the ST segment as seen in the Holter-monitored ECG remains controversial. We have no clear explanation for the lack of protection against ischaemic changes. The effects of profound vasodilatation produced by nifedipine in elderly patients subjected to major surgery, general anaesthesia including administration of enflurane, and a variable amount of blood loss in the postoperative period may be important factors. In conclusion, one should perhaps be cautious of nifedipine administration under these circumstances.

Aneurysm of a peripheral pulmonary artery. Case report and brief review of the literature.

A patient is presented in whom a solitary aneurysm of a peripheral pulmonary artery was treated by left lower lobectomy. This is the eighth reported successful resection of such an aneurysm. A brief review of the literature is also presented and the importance of pulmonary arteriography in the diagnosis of this condition is mentioned.

Haplotypes identified by 10 DNA restriction fragment length polymorphisms at the human low density lipoprotein receptor gene locus.

Ten useful two allele restriction fragment length polymorphisms of the low density lipoprotein receptor gene were used for haplotype analysis in 45 unrelated familial hypercholesterolaemic (FH) patients, 60 normal controls, and 32 FH homozygotes, all of whom were white Afrikaners. Pedigree analysis in 27 informative heterozygous FH and 23 normal families has shown the segregation of at least 17 haplotypes in the normal population (111 chromosomes) compared to a predominant association of two of these haplotypes with the disease in the FH subjects. This association was further confirmed in 32 FH homozygotes, indicating at least two 'founder' members for the disease in the Afrikaner population. Recombination events were not detected in any of the families studied and we thus conclude that the haplotypes associated with FH function as specific markers for the disease and will allow presymptomatic diagnosis in affected families.

The first 6 years of the Tygerberg Hospital lipid clinic.

The Tygerberg Hospital Lipid Clinic was established in July 1983. The demographic characteristics, lipid abnormalities, coronary risk factor profile, treatment status and 6-month follow-up lipid changes of patients seen during its first 6 years are summarised. During this period 329 patients were seen and complete lipograms were available for 312 of them. This patient population, consisting of 87.2% whites and 12.8% coloureds, represented a wide age range (2-69 years), various occupations and the whole spectrum of educational qualifications. The plasma cholesterol levels of 78.8% of the patients could be described as high risk, according to the cholesterol action limits of the Heart Foundation of Southern Africa, and 33.2% had low high-density lipoprotein cholesterol (less than 1 mmol/l) levels. Approximately 20% of the patients had familial hypercholesterolaemia and 31.1% were already on lipid-lowering medication before registration. The Lipid Clinic succeeded in improving the mean overall plasma cholesterol levels by 8% during the 6 months after registration and provided essential information for the planning of treatment strategies for patients with hypercholesterolaemia.

[Ventricular aneurysmectomy and infarctectomy]. / Ventrikulêre aneurismektomie en infarktektomie

During a 22-month period, April 1972 to February 1974, 4 patients underwent ventricular aneurysmectomy at the Karl Bremer and Tygerberg Hospitals for congestive cardiac failure. In addition, 1 patient with an aneurysm and 3 patients with acute myocardial infarcts, ranging from 16 to 28 days postinfarction, underwent emergency surgery for recurrent malignant arrhythmias. The preoperative treatment, cardiac catheterisation data and surgical findings are outlined. The over-all survival rate is 75% for a mean follow-up period of 12,5 months (range 8-22 months). It is concluded that aneurysmectomy, for congestive cardiac failure, and infarctectomy, for life-threatening ventricular arrhythmias, are gratifying and worthwhile procedures.

Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia.

The frequency and inheritance of three restriction fragment length polymorphisms (RFLPs) of the low density lipoprotein (LDL) receptor gene were investigated in 27 South African families with familial hypercholesterolaemia. Four haplotypes, defined by the enzymes PvuII, StuI, and NcoI, were found to segregate in this population. The frequency of the rare allele detected by NcoI was found to be 0.53 in 45 unrelated familial hypercholesterolaemic (FH) patients compared to 0.33 in 60 normal controls (p less than 0.005). In 71% of the families studied, a haplotype with common alleles for PvuII and StuI and the rare allele for NcoI cosegregated with the defective gene. In 20% of the families, a second haplotype with rare alleles for PvuII and StuI and common allele for NcoI segregated with FH. In these families the haplotypes unambiguously cosegregate with the disease and can therefore be used for early diagnosis of FH.