Coronary heart disease risk factors in women.

Despite the obvious predominance of coronary heart disease in middle-aged men, cardiovascular disease including coronary heart disease and cerebrovascular accidents is currently the major cause of death in women (54% cardiovascular mortality, 46% coronary mortality; 28% of all deaths). Before menopause, coronary heart disease is infrequent which suggests that female hormones and metabolism offer protection. Without hormone replacement therapy after menopause women may develop coronary atherosclerosis. Ageing is among the non-modifiable risk factors for coronary heart disease in women, while genetic predisposition and environmental factors remain controversial. The modifiable risk factors are mostly common to both sexes and include heavy cigarette smoking (especially in women under oral contraception) dyslipidaemia, high blood pressure, and diabetes; some factors are peculiar to women. The delayed onset of coronary heart disease in women, roughly 10 years later than in men, and greater feminine longevity (81 years vs 74 in men on average) points to the potential benefit of post-menopause hormone replacement therapy together with reduction of other modifiable risk factors. After menopause, the protective HDL cholesterol decreases whereas high LDL cholesterol, high triglycerides and high blood pressure are major risk factors for coronary heart disease as well as for cerebrovascular accident. The role of hormone replacement therapy in the prevention of cardiovascular disease in women is still controversial despite the results of meta-analyses which suggest a 25% to 44% reduction in coronary heart disease following oestrogen therapy alone or in combination with progestogen, depending on the hormonal regime. In conclusion, menopause, now considered as the marker for the end of natural protection against coronary heart disease, should be followed by early and prolonged combined hormone replacement therapy in order to reduce the low compliance with long-term hormone replacement therapy.

Evaluation of flurbiprofen for prevention of reinfarction and reocclusion after successful thrombolysis or angioplasty in acute myocardial infarction. The Flurbiprofen French Trial.

Thirty-eight coronary care units (CCUs) in France participated in this double-blind, placebo-controlled, multicentre study to assess the efficacy of flurbiprofen, a non-steroidal anti-inflammatory agent (NSAID) with potent anti-platelet activity (PAA), in the prevention and recurrence of myocardial infarction (MI) and reocclusion of the infarct-related artery (IRA) in patients successfully treated for acute MI by thrombolysis and/or coronary angioplasty within 6 h of onset of symptoms. A coronary angiogram was performed within the first 24 h to confirm successful reperfusion. Two hundred and thirty-three patients (group 1) were randomly allocated to flurbiprofen 50 mg twice daily and 228 patients (group 2) to placebo. All patients complied with the entry criteria, and drug treatment was commenced within 48 h of MI. Patients were assessed at 3 weeks, 3 months and 6 months, data being recorded on major clinical events and survival status. Overall mortality was low (1.1%) and similar for both groups, confirming the benefit of early reperfusion therapy. The reinfarction rate documented during the 6-month follow-up was 3% (7/233) in group 1 and 10.5% (24/228) in group 2 (P < 0.001). The need for coronary angioplasty and/or coronary bypass graft was decreased by 51% (group 1: 39/233 = 17%; group 2: 75/228 = 33%) (P < 0.001). Coronary angiogram at 6 months showed a similar reocclusion rate between treatments. Flurbiprofen appears to be an effective drug for the prevention of reinfarction after coronary reperfusion and in reducing the need for secondary revascularization procedures. It may offer advantages over aspirin, but comparable efficacy remains to be established.

[A survey on the management of myocardial infarction in France.The Infarctus Top Chrono Survey]. / Enquête sur la prise en charge des infarctus du myocarde en France. Enquête Infarctus Top Chrono.

An enquiry was carried out between December 1989 and January 1990 involving 749 cardiologists and 8,846 general practioners based throughout France to evaluate the number of myocardial infarctions diagnosed each year, to determine how the patients are transported to hospital and to assess the average delays of transportation. This enquiry showed that cardiologists diagnosed 15 cases of myocardial infarction per year: their first reflex is to visit the patient, sometimes accompanied by the emergency medical service if available at the time of the patient's call, or to advise the patient to call the emergency service straight away if it is not possible for them to visit the patient immediately. The delay of transportation is less than 30 minutes in 45% of cases and over 60 minutes in 10% of cases. Regional differences were observed and are analysed. General practitioners diagnose 4 cases of myocardial infarction per year: the principal attitude is the same as that of the cardiologists, except that the general practitioner is available to visit the patient more often and is called out more easily. The means of transport and the delays of transportation are very similar to those observed with the cardiologists. This analysis of the management of myocardial infarction in France in 1990 may help organise actions to shorten the time between the onset of chest pain and the institution of thrombolytic therapy.

Thrombosis and thrombolysis in unstable angina.

Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures.

Invasive reperfusion study. II. Multicentre European randomized trial of anistreplase vs streptokinase in acute myocardial infarction.

IRS II (Invasive reperfusion study II) was a multicentre randomized trial comparing the efficacy of a 2-5-min 30 U anistreplase intravenous injection with a 1,500,000 U 60-min streptokinase (SK) intravenous infusion in acute myocardial infarction. 116 patients were randomized within 6 h of onset of symptoms. Early coronary patency was assessable in 107 patients by coronary angiogram performed 102 min after thrombolytic treatment (range: 30-297 min) in the anistreplase group and 93 min (range: 22-330 min) in the SK group. The early coronary patency rate was significantly higher in the anistreplase group than in the SK group: respectively, 70% (38/54) and 51% (27/53), P less than 0.05). Fifty patients had assessable coronary angiograms at 90 min and 24 h. The 24-h patency rate was 92.3% (24/26) in the anistreplase group vs 87.5% (21/24) in the SK group. No early reocclusion occurred in the anistreplase group vs 15.4% (2/13) in the SK group (NS). Fibrinogen fell to 13.2 +/- 19.8% on anistreplase vs 9.4 +/- 10.3% on SK (NS). Bleeding complications occurred in 12% (7/58) of treated patients in the anistreplase group vs 20.7% (13/58) in the SK group (NS). Two cerebrovascular accidents occurred after thrombolytic treatment with anistreplase (3.4%) vs one after SK (1.7%) (NS). Thus, anistreplase is more effective than intravenous SK and easier to administer.

[An often ignored complication of left heart catheterization: embolism of cholesterol crystals. Report of 9 cases]. / Une complication souvent méconnue du cathétérisme gauche: les embolies de cristaux de cholestérol. A propos de 9 observations.

Cholesterol embolism (CE) is caused by the migration of cholesterol crystals from severe atheromatous lesions. Until recently, this was considered to be a classical but rare complication of atheroma. With the upsurge in techniques of left heart catheterization there has been a regain of interest in this subject. Nine cases of cholesterol embolism occurring after left heart catheterisation are reported, 3 after coronary angioplasty, and 3 cases after associated thrombolytic therapy. Three patients developed cutaneous syndromes (livedo reticularis, the "purple toe syndrome") with a favorable outcome in a few weeks. Two patients developed segmental necrosis of the small bowel requiring surgical resection of the affected area. Finally, in 4 cases, the patients died 12 hours to 3 months after catheterization: 2 patients had polyvisceral involvement; one patient developed cardiogenic shock; one patient had intestinal necrosis involving 2/3 of the ileum and the right colon. The cases illustrate the variability of the presentation of CE and its potential gravity. At present, the only effective measures are prophylactic; curative treatment remains particularly disappointing.

[Tissue plasminogen activator (alteplase) in acute massive pulmonary embolism. A pilot study]. / Activateur tissulaire du plasminogène (alteplase) dans l'embolie pulmonaire aiguë massive. Etude pilote.

Twenty six patients with acute (less than 5 days) pulmonary embolism (PE) confirmed by bilateral pulmonary angiography with a Miller index greater than 15 were given tissue plasminogen activator (Alteplase) (rt-PA) intravenously (n = 20) or directly into the pulmonary artery (n = 6). The dosage was 100 mg/7 hours (bolus 10 mg + 40 mg/2 hours + 50 mg/5 hours). Heparin (5000 IV as a bolus and 1000 IV/hour) was associated in all cases. The Miller index decreased from 24 +/- 1 (n = 26) before treatment to 12 +/- 1 (n = 25) (p less than 0.001) after 100 mg of Alteplase, and from 25 +/- 0.4 (n = 14) to 22 +/- 0.5 (n = 14) (p less than 0.001) after 50 mg. The mean pulmonary arterial pressures fell from 30 +/- 2 mmHg to 21 +/- 2 mmHg after 50 mg (n = 26) (p less than 0.001) and to 14 +/- 1 (n = 25) (p less than 0.001) after 100 mg of Alteplase. A decrease in mean pulmonary artery pressures (-22%, p less than 0.001) and total pulmonary resistances (-29%, p less than 0.001) was obtained after one hour of thrombolysis in 12 monitored patients. There were no fatalities. Severe haemorrhage occurred in 6 cases. Therefore, Alteplase induced a rapid dissolution of recent intrapulmonary thrombi without inacceptable haemorrhagic complications. Its action could be particularly beneficial in patients with right ventricular failure due to life threatening pulmonary embolism.

[A european multicenter and randomized study of APSAC versus streptokinase in myocardial infarction]. / Etude européenne multicentrique et randomisée de l'APSAC versus streptokinase dans l'infarctus du myocarde.

In a multicentre randomized open study conducted on two parallel groups the effectiveness of APSAC was compared with that of streptokinase (SK) in 116 cases of myocardial infarction treated during the first 2.75 hours. APSAC (30 IU) was administered by intravenous bolus injection over 2 to 5 minutes, and SK (1.5 million IU) by intravenous infusion over 60 minutes. The patency of the coronary artery responsible for myocardial infarction was evaluated by coronary arteriography performed 1.74 h on average after the beginning of treatment; it was 70 p. 100 in the APSAC group and 51 p. 100 in the SK group (p less than 0.05). The fall in plasma fibrinogen was similar in both groups (mean minimum level; 0.2 g/l). Haemorrhages occurred in 9/58 patients treated with APSAC (15.5 p. 100) and in 13/58 patients treated with SK (22.4 p. 100); these haemorrhages took place during the first 24 hours in 4 patients of the APSAC group and in 10 patients of the SK group. Five patients died: 2 in the APSAC group and 3 in the SK group. In a subgroup of 38 patients who underwent 3 control coronary arteriographies (at 90 min, 24 hours and 3 weeks), the patency rates were 63 p. 100, 82 p. 100 and 93 p. 100 respectively with APSAC and 44 p. 100, 86 p. 100 and 92 p. 100 respectively with SK (NS). No coronary reocclusion occurred in the APSAC group, as against 3 (1 early, 2 delayed) in the SK group. It is concluded that APSAC seems to be more effective than intravenous streptokinase; it is easier to administer (bolus injection) and does not carry a higher risk of haemorrhage.

Thrombolytic treatment of acute pulmonary embolism.

Many investigators have reported about beneficial results with thrombolytic therapy in patients with acute pulmonary embolism. Streptokinase and urokinase have been used for more than 15 years, but the conditions of use of these agents still remain controversial. Optimal dosage and treatment schedule are still evolving. For streptokinase most investigators adopt a fixed dosage schedule: a loading dose of 250,000 units followed by a maintenance infusion of 100,000 units per hour for 24 to 72 hours. For urokinase numerous dosage regimens have been used such as: high dosage schedule 4,400 units per kilogram per hour for twelve to 24 hours with or without loading dose; moderate dosage 1,600 to 2,000 units per kilogram per hour for 24 hours and low dosage in bolus. With these treatments there is a trend to reduced in-hospital-mortality in massive pulmonary embolism; the early pulmonary revascularization and the hemodynamic improvement are higher than those noticed with heparin. These results are obtained with a minimum of complication essentially bleeding in 10 or 15%; most bleeding being located at puncture site. More recently, new thrombolytic agents have been used in acute pulmonary embolism. Only four studies have tested rt-PA which is effective and relatively safe, but the optimal dose regimens remain to be determined. Less information is available concerning Anisoylated Plasminogen Streptokinase Activator Complex (APSAC), the angiographic improvement seems to be rapid and important (50% on average) but the decrease of fibrinogen is important too and comparable with streptokinase. Considering the good results of thrombolytic treatment of acute submassive and massive pulmonary embolism, there is a doubt as to whether the pulmonary embolectomy has any place in the pulmonary embolism patients except in those with cardiac arrest. In the near future new thrombolytic drugs could be more efficient on pulmonary embolism and deep venous thrombosis, and thus the bleeding risk might be decreased.

[Treatment of acute pulmonary embolism with a low molecular weight heparin by the intravenous route. Study of the optimal dosage]. / Traitement des embolies pulmonaires aiguës par une héparine de bas poids moléculaire par voie intraveineuse. Recherche de la posologie optimale.

Experimental studies on rabbits have shown that CY 222, a low molecular weight heparin (mean: 2.500 daltons), has the anti-thrombosis properties of heparin but reduces the risk of haemorrhage in optimal doses of 1.000 AXa IC (Institut Choay) units/kg/day. The safety and effectiveness of CY 222 were tested in 47 patients presenting with a less than 5 days' old pulmonary embolism. The patients were divided into three groups according to dosage: group I (n = 16) received 500 AXa ICu/kg/day; group II (n = 17), 750 AX ICu/kg/day, and group III (n = 14), 1.000 AXa ICu/kg/day. The drug was administered by continuous intravenous infusion during 10 days. Its effectiveness was assessed from the Miller index calculated on conventional pulmonary angiograms on days 0, 5 and 10. On the 10th day of treatment, the percentage of revascularization was similar in all three groups (group I 65.9 +/- 9.9 p. 100; group II 71 +/- 6.8 p. 100; group III 68 +/- 8.5 p. 100), but the improvement was significantly more rapid in group III patients. Embolism recurred in 5 cases (2 in group I, 1 in group II, 2 in group III) and was fatal in 1 case (group I). Haemorrhagic complications were noted in 3 cases (group III patients). Except for thromboelastography, all coagulation tests were unmodified by CY 222. The anti Xa and the (very low) anti IIa activities of the drug were directly related to the doses administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous anisoylated plasminogen streptokinase activator complex versus intravenous streptokinase in evolving myocardial infarction. Preliminary data from a randomised multicentre study.

The efficacy of a single intravenous bolus of anisoylated plasminogen streptokinase activator complex (APSAC 30U in 4 to 5 minutes) versus an intravenous infusion of streptokinase (1.5 X 10(6) U in 60 minutes) was assessed in 86 patients with evolving myocardial infarction of less than 6 hours duration in a cooperative randomised study. The patency of the infarct-related artery was assessed by coronary angiography at, on average, 90 minutes after therapy (mean time: APSAC 95 minutes, streptokinase 105 minutes). The treatment groups were similar with respect to sex, age, location of myocardial infarction and the delay from onset of pain to treatment. The 90-minute patency rate (grade 2 to 3) was 71.8% in the APSAC group and 55.8% in the streptokinase group; the difference was not statistically significant. There was no difference between the drop in fibrinogen concentrations in the 2 groups at 3 or 24 hours. The minimal concentration obtained at the first assessment was +/- 0.2 g/L in the streptokinase group and 0.5 g/L in the APSAC group. One patient in the APSAC group, who had a previous meningeal bleeding, had a non-fatal cerebrovascular accident. In a subgroup of 38 patients who had 3 control coronary angiograms at 90 minutes, 24 hours and 3 weeks, the patency rate was 63, 82 and 93%, respectively, in the APSAC group and 48, 88 and 92%, respectively, in the streptokinase group (the difference was not statistically significant). None of the patients in the APSAC group presented with reocclusion, whilst 3 patients in the streptokinase group had reocclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thrombolysis in myocardial infarction. Current status. Prospects]. / La thrombolyse dans l'infarctus du myocarde. Etat actuel. Perspectives.

Numerous data and controversies have arisen from studies concerning thrombolysis in acute myocardial infarction over the past five years. It is known that coronary artery obstruction is present in approximately 90 percent of acute infarctions during the first 4 hours of onset. Spontaneous renewed flow is noted in 30 percent of cases following the 12th hour, and in 50 percent of cases following the 3rd week. It is possible to obtain early renewed flow in 85 percent of cases with the administration of intracoronary streptokinase, and in 55 to 70 percent of cases with parenteral administration of streptokinase or urokinase. Controversy centers around the effectiveness of thrombolysis in limiting the size of the infarction, thus preserving cardiac function. Due to the numerous different protocols used and the insufficient number of cases reported in randomized studies, it is not possible to determine the superiority of one technique over another in preserving ischemic myocardium. After taking into account the technical constraints of the procedure and the contradictory published results, therapeutic fibrinolysis should remain a research modality as long as its effectiveness in preserving ischemic myocardium has not been established.