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Biomedical subjects

J C Kaski

Publications and source records attributed to J C Kaski.

At least 73 records · Page 4Linked to original sources
PubMed1998

Low dose imipramine improves chest pain but not quality of life in patients with angina and normal coronary angiograms.

AIMS: We investigated patients with chest pain and normal coronary angiograms to determine whether low dose imipramine prescribed as add-on therapy to conventional anti-anginals reduced the incidence of chest pain and whether this led to an overall improvement in quality of life. METHODS AND RESULTS: We performed a randomized, double-blind, cross-over trial of imipramine 50 mg daily vs placebo in 18 women (median age 53 years; range 35-72) with chest pain and normal coronary angiograms who were suffering at least two anginal episodes per week despite conventional anti-anginal medication. Each treatment phase lasted 5 weeks and the incidences of chest pain and side effects were carefully recorded. Quality of life was monitored using a validated health profile questionnaire scoring perceived distress in six domains (pain, energy, mobility, sleep, emotional reactions and social isolation). The total number of chest pain episodes was significantly less during active treatment compared to placebo [11 (3-22) vs 21 (16-28)--median (interquartile range); P = 0.01]. However, a high incidence (83%) of side effects was reported during active treatment and three patients had to be withdrawn from the study as a consequence. No significant improvement was detected in any of the six quality of life domains when imipramine was compared to placebo. CONCLUSION: Imipramine reduces the incidence of chest pain in patients with chest pain and normal coronaries who remain symptomatic despite conventional anti-anginal therapy. The failure to demonstrate associated improvements in quality of life may have been due to the high incidence of side effects.

Adult↗
PubMed1998

Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome.

AIMS: Thallium-201 perfusion abnormalities are common in patients with hypertrophic cardiomyopathy and may be associated with an adverse prognosis in the young. The aim of this study was to prospectively determine the relationship between thallium-201 defects during dipyridamole stress to clinical presentation and outcome in a large consecutive series of patients with hypertrophic cardiomyopathy. METHODS/RESULTS: Thallium-201 single photon computed tomography was performed in 216 patients with hypertrophic cardiomyopathy during dipyridamole stress (0.5 mg. kg-1). Fixed perfusion defects occurred in 25%, and reversible defects in 22%. A combination of defects was present in 7%. Fixed defects were associated with: a history of syncope (17 of 46 with, vs 36 of 170 without syncope, P = 0.03); larger left ventricular end-diastolic (46.9 +/- 7.4 mm vs 43.3 +/- 6.4 mm; P = 0.001) and end-systolic dimension (30.2 +/- 8.4 mm vs 24.5 +/- 5.9 mm, P < 0.0001); increased left atrial diameter (46.1 +/- 8.1 mm vs 40.5 +/- 7.7 mm, P < 0.0001); lower fractional shortening (35.9 +/- 10.4% vs 43.8 +/- 8.6%, P < 0.0001): and lower maximal exercise oxygen consumption (24.2 +/- 8.1 ml. min-1. kg-1 vs 29.4 +/- 8.8 ml. min-1. kg-1, P < 0.0003). Reversible defects did not correlate with symptomatic status, but were associated with: larger left atrial dimensions (44.5 +/- 8.1 mm vs 41.0 +/- 8.0 mm; P = 0.009) and greater maximal left ventricular wall thickness (24.0 +/- 7.0 mm vs 20.6 +/- 7.0 mm, P = 0.003). The mean follow up time was 41 +/- 21 months, range 0.6-124. There was no association between any thallium-201 abnormality and disease related death in young or adult patients. CONCLUSION: The present study shows that fixed thallium-201 perfusion defects detected during dipyridamole stress in patients with hypertrophic cardiomyopathy are associated with syncope, larger left ventricular cavity dimensions and reduced exercise capacity. Although the event rate was relatively small, there was no evidence for an association between thallium-201 defects and survival.

Adolescent↗
PubMed1998

Angiographic progression in patients with angina pectoris and normal or near normal coronary angiograms who are restudied due to unstable symptoms.

BACKGROUND: Syndrome X patients commonly remain symptomatic during follow-up and may be readmitted with unstable anginal symptoms. Angiographic disease progression must be considered as a possible mechanism for instability, particularly where multiple coronary risk factors are present and an interval of several years has elapsed since previous angiography. METHODS AND RESULTS: We reviewed data from 139 consecutive patients with chest pain and normal or near normal coronary angiograms (101 patients with completely normal angiograms and 38 patients with minimal lumenal irregularities). During a 5-year period, 24 patients (19 women, median age 56 years) underwent repeat angiography due to primary unstable angina (median interval between angiograms 58 months (range 8-130 months)). This group included three patients with minimal lumenal irregularities and four patients with left bundle branch block. Only two patients had progression to significant angiographic stenosis (> 30% diameter reduction); both were male patients with minimal irregularities at baseline angiography, left bundle branch block and multiple coronary risk factors. However, overall only two of 18 (11%) patients with one or more conventional coronary risk factors had angiographic progression. CONCLUSIONS: Unstable symptoms in patients with chest pain and previously normal or near normal coronary arteriograms are rarely due to angiographic disease progression. However, the presence of minimal lumenal irregularities at baseline angiography and LBBB may identify a sub-group at increased risk.

Adult↗
PubMed1998

Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation.

BACKGROUND: Unstable angina is a heterogeneous clinical syndrome. The diverse clinical presentations of unstable angina may reflect different pathogenic mechanisms within the plaque. OBJECTIVE: To investigate the cellular constituents of culprit coronary atheromatous plaques in patients with stable angina pectoris and patients with diverse clinical presentations of unstable angina. METHODS: 48 patients who underwent coronary atherectomy for management of ischaemic heart disease: 23 had stable angina and 25 had unstable angina. Of the latter, 11 patients were classified as Braunwald's IIB and 14 as Braunwald's IIIB unstable angina. The presence of thrombus, cholesterol clefts, and smooth muscle cell proliferation was assessed in atherectomy samples using standard histological techniques. Monoclonal antibodies were used to identify smooth muscle cells and macrophages within atherosclerotic plaque fragments. RESULTS: Fresh thrombus was more frequently found in patients with Braunwald's IIIB unstable angina (64%) than in patients with stable angina (22%) or IIB unstable angina (27%) (p < 0.0006). A pattern of smooth muscle cell proliferation ("accelerated progression pattern") was observed which was also associated with coronary thrombus. This pattern was present in 30% of patients with stable angina, 64% of patients with IIIB unstable angina, and in all patients (100%) with IIB unstable angina. Atherosclerotic plaques with thrombus, cholesterol clefts, and macrophages were more common in patients with unstable angina than in stable angina patients. CONCLUSION: The presence of a specific smooth muscle cell proliferation (accelerated progression) pattern in patients with unstable angina, particularly in those with Braunwald's IIB unstable angina, suggests that episodic plaque disruption and subsequent healing may be an important mechanism underlying angina symptoms in these patients.

Adult↗
PubMed1998

Regional variations in endothelin-1 and its receptor subtypes in human coronary vasculature: pathophysiological implications in coronary disease.

Endothelin-1 is a potent vasoconstrictor peptide and mitogen for vascular smooth muscle cells. Increased plasma or tissue levels of endothelin-1 have been described after myocardial infarction and in atherosclerosis, suggesting that this peptide may play a pathophysiological role in various coronary syndromes. Here, we have studied regional variations in ET-1 and its receptors in control and atherosclerotic human coronary vasculature using standard immunohistochemistry and in vitro autoradiography. ET-1 immunoreactivity was associated with luminal endothelial cells and smooth muscle cells at regions of atherosclerosis. ET(A) receptors were present on smooth muscle cells of coronary arteries and on cardiac myocytes. Medial ET(B) receptor binding at the proximal region of coronary arteries was weak, but increased significantly towards distal regions of this vessel (p<0.005 in control and p<0.0005 in ischaemic heart disease). Microvascular endothelial cells in the adventitia of coronary arteries, myocardial microvessels and the endocardial endothelium expressed the ET(B) receptor exclusively. The receptor variations revealed in this study provide supporting evidence that ET-1 is associated with (1) vascular smooth muscle and endothelial cell proliferation, including areas of intimal hyperplasia and regions of neovascularization (2) increased ET-1-induced reactivity of distal portions of the human coronary artery, (3) ET-1-mediated constriction of myocardial microvessels. These results provide new insights into different potential roles for this peptide in healthy and diseased human coronary vasculature.

Autoradiography↗
PubMed1998

Methylenetetrahydrofolate reductase polymorphism (C-677T) and coronary artery disease.

1. Many studies have shown that hyperhomocysteinaemia is a risk factor for atherosclerotic vascular disease. A mutation (C-677T) in the gene coding for the methylenetetrahydrofolate reductase (MTHFR) enzyme has been shown to produce a thermolabile form of the enzyme. Homozygosity for this mutation has been correlated with an elevated plasma homocysteine concentration. The present study aimed to determine whether this mutation was a risk factor for coronary artery disease (CAD). This was achieved by comparing the frequency of the C-677T mutation in patients with angiographically proven CAD against angiographically normal patients in two separate U.K. samples. The analysis was repeated with CAD patients split into those with >=99% stenosis of arteries and those without, to establish whether the C-677T mutation could be correlated with severity of CAD.2. Two patient groups were selected from London and Sheffield. The London group comprised 174 cases and 148 controls. The Sheffield group comprised 93 cases and 85 controls. The DNA samples of the patients were genotyped by polymerase chain reaction and restriction enzyme digestion.3. For London the homozygous C-677T frequencies were: 0.07 (controls), 0.09 (CAD without >=99% stenosis) and 0.10 (CAD with >=99% stenosis). For Sheffield the homozygous C-677T frequencies were: 0.08 (controls), 0.10 (CAD without >=99% stenosis) and 0.11 (CAD with >=99% stenosis). No association was found between the C-677T mutation and CAD in our sample geographical groups. Statistical comparison by genotype distribution for 0 VD (no vessel disease, i.e. 0% diameter reduction in all epicardial arteries) versus CAD without >=99% stenosis: London, P=0.19; Sheffield, P=0.53; 0 VD versus CAD with >=99% stenosis: London, P=0. 23; Sheffield, P=0.55.

Aged↗
PubMed1997

Serum endothelin levels and pain perception in patients with cardiac syndrome X and in healthy controls.

The possible algogenic effects of elevated serum endothelin levels in cardiac syndrome X were investigated in a case-control study that examined somatic pain perception in the forearm during submaximal effort tourniquet and cold immersion tests. Pain threshold to both ischemic and cold stimulation of the forearm was demonstrated to be significantly lower in patients with syndrome X than in matched healthy controls, and a negative correlation between ischemic pain threshold and endothelin levels was demonstrated.

Aged↗
PubMed1997

Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction.

BACKGROUND: The clinical significance of the association between elevated anti-Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is unclear. We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI). The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients. METHODS AND RESULTS: We screened 220 consecutive male survivors of MI for anti-Cp antibodies. Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at > or = 1/64 dilution. Patients with persisting seropositivity of > or = 1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or 500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial. The incidence of adverse cardiovascular events (over a mean follow-up period of 18+/-4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to 15.5; P=.03). In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6, P=NS). Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group (P=.02). CONCLUSIONS: An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients. Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.

Administration, Oral↗
PubMed1997

Heart rate-independent prolongation of QTc interval in women with syndrome X.

BACKGROUND: Cardiac syndrome X is usually diagnosed in the presence of typical exertional chest pain, a positive response to exercise testing, and normal coronary angiograms. The underlying pathogenic mechanisms are speculative, but myocardial ischemia and increased sympathetic activity have been implicated. HYPOTHESIS: The present study examined whether QTc interval is prolonged in women with syndrome X when confounding factors such as heart rate, gender, and environmental conditions are accounted for. METHODS: Maximum QTc interval and its relationship to clinical and exercise variables were evaluated in 32 women with syndrome X (exertional chest pain, positive exercise testing, and completely normal coronary arteries) and 34 normal controls. RESULTS: Patients with syndrome X had significantly longer QTc interval (440 +/- 24 ms) than normal subjects (410 +/- 26 ms, p < 0.004). However, this QTc prolongation appears to be heart rate-independent as patients with syndrome X showed longer QT and QTc intervals than controls despite an identical heart rate. No relation was found between QTc prolongation and clinical or exercise test variables in patients with syndrome X. CONCLUSION: Although increased sympathetic drive is present in syndrome X, and this variable is likely to modulate QTc duration, the mechanism and clinical implications of QTc interval prolongation in syndrome X remain speculative.

Case-Control Studies↗
PubMed1997

Polymorphism in apolipoprotein(a) kringle IV 37(Met/Thr): frequency in a London population and its association with coronary artery disease.

BACKGROUND: A raised concentration of lipoprotein(a) [Lp(a)] in human plasma has been considered as a risk factor for coronary artery disease (CAD). Apolipoprotein(a) and plasminogen genes are exceptionally similar to a variable number of plasminogen-like kringle IV repeats in the apo(a) gene. Polymorphisms have been previously identified in the apolipoprotein(a) kringle IV 37. HYPOTHESIS: In order to determine the frequency of the apolipoprotein(a) kringle IV 37 Met66-->Thr polymorphism in a London-based population and to assess the relationship of this polymorphism with CAD in Caucasian patients, we genotyped two groups of people of different ethnic origin (Caucasian and Afro-Caribbean) for the mutation using standard polymerase chain reaction (PCR) techniques. METHODS: The first group consisted of 182 unrelated Caucasian patients (107 men and 75 women, mean age 59.7 +/- 10.2 years) recruited at St. George's Hospital. They were defined as patients with 0, 1 or > or = 2 vessel disease patients depending on the degree of stenosis in none, one, or several major epicardial arteries. The second group comprised 64 unrelated patients of Afro-Caribbean origin attending a hypertension clinic at St. George's Hospital. RESULTS: It was shown that the prevalence of the Met66-->Thr mutation is markedly higher in Caucasians than in Afro-Caribbeans and that this mutation is not associated with either Lp(a) levels or severity of CAD.

Aged↗
PubMed1997

Effect of magnesium sulphate in patients with unstable angina. A double blind, randomized, placebo-controlled study.

AIMS: Administration of intravenous magnesium sulphate has been shown to be protective during acute myocardial ischaemia and it may therefore have beneficial effects in unstable angina. The purpose of this study was to assess the effects of a 24-h infusion of magnesium in patients with unstable angina. METHODS AND RESULTS: Patients who presented with unstable angina with electrocardiographic changes were randomized to receive a 24-h intravenous infusion of magnesium or placebo within 12 h of admission. The primary endpoint was myocardial ischaemia, as assessed by 48 h Holter monitoring. Resting 12-lead ECGs, creatine kinase-MB release and urinary catecholamines were also assessed. Patients were followed for 1 month. Thirty-one patients received magnesium sulphate and 31 placebo. Baseline characteristics and extent of coronary disease were similar in both groups. On 48 h Holter monitoring, 14 patients (50%) had transient ST segment shifts in the magnesium group vs 12 patients (46%) in the placebo group. However, there were fewer ischaemic episodes in the magnesium group (51 vs 101, P < 0.001) and there was a trend towards an increase in the total duration of ischaemia in the placebo group compared to the magnesium group in the second 24 h (2176 min vs 719 min respectively, P = 0.08). Regression of T wave changes on the 24 h ECG occurred more frequently in patients who received magnesium compared to those treated with placebo (11 patients vs 0 patients respectively, P < 0.005). Creatine kinase-MB release was significantly less at 6 and 24 h in patients who received magnesium compared to those treated with placebo. Catecholamine excretion was lower in patients treated with magnesium than in those treated with placebo (adrenaline: 1.05 +/- 0.16 vs 1.61 +/- 0.32 ng.mmol-1 creatinine; noradrenaline: 9.99 +/- 1.82 vs 18.48 +/- 2.41 ng.mmol-1 creatinine respectively in the first 12 h sample, P < 0.05). CONCLUSIONS: Intravenous magnesium reduces ischaemic ECG changes, creatine kinase-MB release and urinary catecholamine excretion in the acute phase of unstable angina. Thus, magnesium may be a beneficial additional therapy for these patients. Further studies are required to confirm these finding.

Adult↗
PubMed1997

Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X).

BACKGROUND: Patients with syndrome X (exertional angina, positive exercise test, normal coronary arteriogram) have an altered perception of cardiac pain. This symptom may arise from increased sensitivity to adenosine. Previous studies suggest that intravenous aminophylline (an adenosine receptor blocker) improves exercise tolerance in patients with this disorder. OBJECTIVE: To examine the efficacy of oral aminophylline in syndrome X. METHODS: 13 patients (11 women and two men, mean (SD) 54 (6) years) with syndrome X were studied. Patients were randomised in a double blind crossover study to receive either oral aminophylline or placebo for three weeks. All patients underwent symptom limited exercise testing and ambulatory electrocardiography at the end of each three week period. RESULTS: 10 patients completed the study. The time to angina during exercise testing in patients who were given aminophylline was longer than for the placebo group (mean (SD) 632 (202) seconds v 522 (264) seconds, P = 0.004). Peak exercise ST depression did not differ significantly between patients who received aminophylline and those administered placebo (mean (SD) -1.9 (0.7) mm v -1.5 (0.8) mm). Six patients taking aminophylline reported a reduction in the total number of episodes of chest pain during the three weeks, but the frequency and duration of ST segment depression during Holter monitoring was unchanged. CONCLUSION: Oral aminophylline has a favourable effect on exercise induced chest pain threshold in patients with syndrome X. The disparate effects on symptoms and ST segment changes are intriguing and further study is warranted.

Administration, Oral↗