Spontaneous remission is a frequent outcome of variant angina.

To assess the prevalence of spontaneous remission in variant angina, 100 patients with this diagnosis who had undergone coronary arteriography in the hospital and a follow-up of at least 1 year were studied. Patients with coronary bypass surgery or myocardial infarction were excluded. Remission was diagnosed in 45 of the 100 patients who had been angina-free and had had no treatment for more than 3 months (mean 18.3). The other 55 patients were receiving medical treatment; 37 had been angina-free for at least 6 months (mean 22.5) and angina persisted in 18. The persistent angina group had a lower prevalence of organic coronary stenoses 70% or greater: 4 of 18 versus 22 of 45 and 22 of 37 for the other two groups (p less than 0.05), and a longer history of rest angina before admission. The remission group contained more patients (17 of 45 versus 4 of 55 [p less than 0.001]) whose attacks had been documented only by provocative testing. Rest angina recurred when calcium antagonist drugs were discontinued in 15 of 51 instances, within 1 month in 11 patients and later in 4 patients. Remission was eventually attained in 35 of the 38 patients in whom these drugs were stopped. These results indicate that remission is a frequent outcome of variant angina. This fact should be considered in the evaluation of the long-term results of treatment and in the planning of care for an individual patient.

Myocardial infarction in patients with previous coronary artery bypass surgery.

An increasing proportion of patients hospitalized with myocardial infarction have previously undergone coronary artery bypass surgery. To define this subgroup, 77 patients with acute infarction occurring 2 or more months (mean 52.8) after bypass surgery were compared with 77 control patients with infarction. Baseline characteristics of the groups were similar except that post-bypass patients were more often men (p = 0.02) and more likely to have had a previous infarction (37 versus 21, p = 0.008). Infarct size was smaller in the post-bypass group as assessed by peak creatine kinase (CK), peak CK-MB, maximal number of electrocardiographic leads with ST elevation, maximal summed ST elevation and QRS score measured 7 to 10 days after admission (p less than 0.001 for each variable). Five control patients but none of the post-bypass patients died in the hospital (p = 0.06). Serious complications (death, acute heart failure, ventricular fibrillation, second or third degree atrioventricular block) occurred in 24 control patients but in only 5 post-bypass patients (p less than 0.001). Angiography was performed after infarction in 45 of the 77 post-bypass patients. Occlusion of both a native coronary artery and its graft was found in 24 of the 45; these patients had had higher peak CK levels (p = 0.008) than the other 21 patients who had angiography. The probable causes of infarction in these 21 were disease progression in nonbypassed arteries or graft occlusion with arterial stenosis, or vice versa, and disease progression distal to a patent graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary angiographic significance of left anterior fascicular block during acute myocardial infarction.

The clinical and angiographic significance of isolated left anterior fascicular block occurring during the early stage of acute myocardial infarction was studied in 141 consecutive patients who underwent cardiac catheterization before hospital discharge. Left anterior fascicular block occurred in 15 of the 62 patients with an anterior wall infarction and in 13 of the 79 with an inferior infarction. None of the clinical characteristics differed among patients with or without left anterior fascicular block. The number of coronary vessels with significant stenosis, the Friesinger and the Gensini scores for severity of stenosis and the ejection fraction were also similar in the two groups. Patients with left anterior fascicular block had more severe narrowing of the coronary artery supplying the infarct zone (88 +/- 21 versus 70 +/- 35%, p less than 0.001) and tended to have less developed collateral circulation (collateral score 0.7 +/- 0.8 versus 1 +/- 0.8, p = 0.10). A significant stenosis of the left anterior descending coronary artery was found as frequently in patients with as in those without left anterior fascicular block (64 versus 65%); 29% of the patients with inferior wall infarction and left anterior fascicular block had left anterior descending coronary artery stenosis compared with 47% of the patients without this conduction disturbance (no significant difference). When the infarction was located anteriorly, a significant stenosis of the proximal segment of the left anterior descending coronary artery was present in 47% of the patients with and in 45% of the patients without left anterior fascicular block.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial exercise testing in patients with effort angina: variable tolerance, fixed threshold.

To investigate the frequency and mechanism of variable threshold angina, seven treadmill exercise tests were performed in each of 28 patients with stable effort angina and exercise-induced ST segment depression. Each patient had tests at 8 AM on 4 days within a 2 week period and on 1 of these days had three additional tests at 9 AM, 11 AM and 4 PM. Time to 1 mm ST depression increased from 277 +/- 172 seconds on day 1 to 319 +/- 186 seconds on day 2, 352 +/- 213 seconds on day 3 and 356 +/- 207 seconds on day 4 (p less than 0.05). Rate-pressure product at 1 mm ST depression remained constant. Similarly, time to 1 mm ST depression increased from 333 +/- 197 seconds at 8 AM to 371 +/- 201 seconds at 9 AM and to 401 +/- 207 seconds at 11 AM and decreased to 371 +/- 189 seconds at 4 PM (p less than 0.01). Again, rate-pressure product at 1 mm ST depression remained constant. The standard deviation for time to 1 mm ST depression, calculated as a percent of the mean for each patient's seven tests and then averaged for the entire group, was 22 +/- 11%. The standard deviation for rate-pressure product at 1 mm ST depression, calculated in the same way, was significantly less at 8.4 +/- 2.8% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A dose-ranging, placebo-controlled, double-blind trial of nisoldipine in effort angina: duration and extent of antianginal effects.

Maximal treadmill exercise testing at 1, 3 and 8 hours was used to assess the onset, duration and antianginal efficacy of the dihydropyridine slow channel calcium-blocking agent, nisoldipine, in an oral dose range of 5, 10 and 20 mg. A double-blind, randomized, placebo-controlled design was used involving 12 patients with stable effort angina. Exercise tolerance was significantly increased 3 hours after each dose, when the maximal beneficial effect occurred. The improvement was observed as early as 1 hour after the 10 and 20 mg dose, and persisted for 8 hours after the 20 mg dose. At 3 hours, the onset of an exercise-induced ST segment depression of 0.1 mV or greater was increased by 62 (p less than 0.05), 75 (p less than 0.01) and 117 seconds (p less than 0.01) with the 5, 10 and 20 mg dose of nisoldipine, respectively, compared with placebo. Similarly, time to onset of angina was significantly increased. The sum of exercise-induced ST segment depression at peak exercise was significantly decreased (p less than 0.05) from 8.7 +/- 2.3 to 6.7 +/- 1.8 and 6.4 +/- 2.0 mm, respectively, after the 10 and 20 mg dose of nisoldipine. The rate-pressure product was significantly greater with nisoldipine than with placebo at the onset of ischemia and at peak exercise (22.8 +/- 1.1 versus 20 +/- 1.4 X 10(3) U for the 20 mg dose; p less than 0.01). Thus, nisoldipine is an effective antianginal agent with a rapid onset of action that improves exercise tolerance, increases angina threshold and persists for at least 8 hours after oral dosing.

Limited usefulness of intermittent nitroglycerin patches in stable angina.

The efficacy of continuous and intermittent nitroglycerin patches (10 mg/day) was compared in a randomized, placebo-controlled trial in 36 patients with stable angina and reproducible, exercise-induced ST depression. Intermittent treatment was administered either 18 or 14 h/day with an intermission of 6 h or 10 h, respectively. Exercise tests were performed during the last 2 h of patch application. Compared with placebo, neither continuous nitroglycerin nor the two intermittent regimens prolonged total treadmill time or time to 1 mm ST depression. No treatment eliminated exercise-induced ST depression in greater than 1 of the 36 patients. Time to angina was prolonged (by 40 +/- 66 s) only during the "10 h off" treatment (p = 0.001); time to angina increased by greater than or equal to 20% in 13 patients. Responders to treatment could be predicted by a short history of angina (p less than 0.05) and a time to angina less than or equal to 250 s during the placebo test. For each treatment, greater than or equal to 25 of the patients reported headache; 4 additional patients dropped out because of severe headache and 2 others because of a coronary event in a washout period. Thus, in most patients with stable angina, side effects outweight any benefit demonstrable with this therapy.

A randomized study comparing propranolol and diltiazem in the treatment of unstable angina.

One hundred consecutive patients hospitalized in the coronary care unit for unstable angina, excluding patients with Prinzmetal's variant angina, were randomized within 24 hours of admission to treatment with diltiazem (50 patients) or propranolol (50 patients). Also excluded were patients with previous coronary artery bypass surgery and those receiving a beta-receptor blocking agent at the time of hospital admission. Left ventricular function and the extent of coronary artery disease were similar in the two groups. During the hospital stay, the number of chest pain episodes decreased from a mean (+/- SD) of 0.75 +/- 0.1 per patient per day to 0.26 +/- 0.07 (p less than 0.05) with diltiazem and 0.29 +/- 0.1 (p less than 0.05) with propranolol therapy. The circadian distribution of chest pain episodes was affected similarly. After 1 month, 14 of the patients treated with diltiazem were symptom-free compared with 13 treated with propranolol. At a mean follow-up time of 5.1 months (range 1 to 15), death had occurred in two patients in each group and myocardial infarction in five diltiazem- and four propranolol-treated patients (difference not significant). Coronary artery bypass surgery had been performed in 21 diltiazem- and 19 propranolol-treated patients (difference not significant). Only 15 patients were symptom-free, 9 treated with diltiazem and 6 with propranolol. This similar result observed with the two forms of treatment suggests that coronary artery spasm may not be the main factor involved in unstable angina when Prinzmetal's variant angina is excluded. It also suggests that diltiazem can be used as an alternative to the usual treatment with beta-receptor blocking drugs.

Clinical and angiographic factors associated with progression of coronary artery disease.

To characterize the clinical and angiographic factors associated with progression of coronary atherosclerosis, 313 consecutive medically treated patients who had had two coronary arteriograms 3 to 119 months (mean 39 +/- 25) apart were studied. One hundred eighty-one patients underwent recatheterization for stable angina, 52 for unstable angina and 80 for various other reasons. In addition to the conventional angiographic features present at the first angiographic study (number of diseased vessels 1.5 +/- 0.8, ejection fraction 59 +/- 11%), an extent score was defined based on the number of coronary segments with 5 to 75% narrowings from a 15 segment coding system. Multivariate logistic regression identified four independent predictors of progression of coronary artery disease: the interval between studies (p less than 0.0001), unstable angina (p less than 0.0001), a high extent score (p = 0.0001) and young age (p = 0.0026). In a subset of 74 patients aged 50 years or younger with, at the time of the first evaluation, an extent score of 4 or more, the probability of progression between 2 and 4 years and after 4 years was, respectively, 80 and 90% compared with 50% for the other patients. Risk stratification for progression of coronary artery disease can thus be obtained.

Comparison of clinical variables and variables derived from a limited predischarge exercise test as predictors of early and late mortality after myocardial infarction.

An exercise test limited to 5 METS or 70% of age-predicted maximal heart rate was performed 1 day before hospital discharge by 225 survivors of acute myocardial infarction, all of whom were subsequently followed up for at least 5 years. The mortality rate was 11.1% during the first year, but averaged only 2.9% per year from the second to fifth year. Over the entire follow-up period, the five variables that predicted mortality by multivariate analysis were QRS score, an exercise-induced ST segment shift, previous infarction, failure to achieve target heart rate or work load and ventricular arrhythmia during the exercise test. Because mortality differed markedly before and after 1 year, Cox regression analyses were performed separately for both of these periods. The factors that were predictive of mortality during the first year were an exercise-induced ST shift (p less than 0.0001, relative risk 7.8), failure to increase systolic blood pressure by 10 mm Hg or more during exercise (p = 0.0039, relative risk 4.3) and angina in hospital 48 hours or longer after admission (p = 0.0046, relative risk 3.4). None of these three variables was predictive of mortality after 1 year. Previous infarction (p = 0.0007), QRS score (p = 0.0042) and ventricular arrhythmia during the exercise test (p = 0.016) were predictive of mortality after the first year. Thus, clinical and exercise test variables are complementary predictors of mortality after myocardial infarction. An abnormal ST segment response during an early limited exercise test and angina in the hospital are common strong predictors of mortality to 1 year, but not thereafter. Late mortality correlates with markers of poor left ventricular function.

Long-term reproducibility and significance of provokable ventricular arrhythmias after myocardial infarction.

The long-term reproducibility and significance of inducible ventricular arrhythmias were assessed in 21 survivors of a myocardial infarction. Programmed ventricular stimulation performed a mean of 12 +/- 2 days (range 8 to 18) after infarction provoked ventricular fibrillation in 2 patients, sustained monomorphic ventricular tachycardia in 8 and nonsustained ventricular tachycardia in 11. Patients were restudied using the same protocol a mean of 8 +/- 2 months (range 4 to 11) after infarction. All patients underwent programmed ventricular stimulation studies in the absence of antiarrhythmic drug treatment. Ventricular tachyarrhythmias could be reinitiated in 16 patients (76%): ventricular fibrillation in 2, sustained ventricular tachycardia in 5 (monomorphic in 4) and nonsustained ventricular tachycardia in 9. A preponderance of inferior infarction was observed among patients with reinducible tachycardias (9 of 16 patients versus 0 of 5 with noninducible tachycardias) (p less than 0.05). No significant difference existed between patients with and without reinducible arrhythmias with respect to severity of coronary artery disease, degree of left ventricular dysfunction, occurrence of ventricular fibrillation in the acute phase of infarction and ventricular arrhythmias detected by 24 hour ambulatory electrocardiographic (Holter) monitoring. There was no significant difference between patients with and without a positive late study in stimulation thresholds, ventricular refractory periods, time interval between initial and repeat testing and use of beta-adrenergic blocking agents. During a mean follow-up period of 17 months (range 10 to 23) one patient with inducible sustained monomorphic ventricular tachycardia at both studies died suddenly. The remaining patients have survived follow-up without experiencing an arrhythmic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term prognosis after myocardial infarction in patients with previous coronary artery bypass surgery.

A group of 205 patients hospitalized with myocardial infarction 2 to 162 months (mean 66) after bypass surgery and 205 control patients with myocardial infarction were compared and followed up for 34 +/- 25 months after hospital discharge. At baseline the postbypass group contained more men (p less than 0.03) and more patients with previous myocardial infarction (p less than 0.06), but the groups were otherwise comparable. Indexes of infarct size were lower in postbypass patients: sum of ST elevation, QRS score, peak serum creatine kinase (CK) (1,115 +/- 994 versus 1,780 +/- 1,647 IU/liter) and peak MB CK (all p less than or equal to 0.001). Postmyocardial infarction ejection fraction was 45 +/- 15% in the postbypass group and 43 +/- 15% in the control group (p = NS); in-hospital mortality rate was 4 and 5%, respectively (p = NS). When patent grafts were taken into account, the two groups were comparable in extent of coronary artery disease. At 5 years after discharge, cumulative mortality was similar in the postbypass and control groups (30 versus 25%, respectively, p = NS). However, postbypass patients had more reinfarctions (40 versus 23%, p = 0.007), more admissions for unstable angina (23 versus 18%, p = 0.04) and more revascularization procedures (34 versus 20%, p = 0.04) than did control patients. The total for these events at 5 years was 70% in the postbypass group and 49% in the control group (p = 0.001). Thus, although patients with previous bypass surgery who develop acute myocardial infarction have a smaller infarct, their subsequent survival is no better than that of other patients with acute myocardial infarction. They experience more reinfarctions and unstable angina. Previous bypass surgery is an important clinical marker for recurrent cardiac events after myocardial infarction.

Percutaneous transluminal coronary angioplasty for the treatment of variant angina.

Among 268 patients undergoing percutaneous transluminal coronary angioplasty between February 1980 and January 1983, a total of 21 patients had variant angina, documented before angioplasty in 14 and after angioplasty in 7. Before angioplasty, all 21 patients had rest angina and 17 also had effort angina; single vessel coronary artery disease with 60 to 95% stenosis was present in all patients and the left anterior descending coronary artery was involved in all but 3 patients. Coronary angioplasty was successful in 19 patients (90%). Eight of the 19 patients remained symptom-free without coronary restenosis after successful angioplasty; in the other 11 patients, angina reappeared within 4 months, usually in association with restenosis. Of the nine patients with coronary restenosis, six had repeat angioplasty (five successful procedures and one failure), two received medical therapy and one underwent coronary bypass surgery. Patients in whom calcium channel antagonists were discontinued immediately after angioplasty had an exceedingly high coronary restenosis rate (8 [80%] of 10 successful attempts), but when calcium antagonists were continued for an average of 6 +/- 4 months after angioplasty, the restenosis rate was low (3 [21%] of 14 successful attempts). After a mean (+/- SD) follow-up period of 33 +/- 13 months, 1 patient had died and the 20 others (95%) were symptom-free; among these 20, 15 patients (75%) had been taking no antianginal drugs for more than 1 year, 2 still received calcium channel antagonists and 3 had had coronary bypass surgery. Repeat coronary arteriography performed 14 +/- 7 months after angioplasty in the 17 patients without angioplasty-related infarction or surgery showed 50% or less coronary stenosis in 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial cell death and apoptosis in hibernating myocardium.

OBJECTIVES: This study was designed to study apoptosis in hypoperfused hibernating myocardium subtending severe coronary stenosis. BACKGROUND: Apoptosis contributes to myocyte death in acute myocardial infarction. METHODS: A left anterior descending coronary artery stenosis was created in 13 pigs and maintained for 24 h (n = 4), 7 days (n = 5) and 4 weeks (n = 4) to reduce coronary blood flow by a mean of 34% with severe regional myocardial systolic dysfunction, as documented by echocardiography. Apoptosis was detected with an in situ end-labeling method and confirmed by "deoxyribonucleic acid laddering" on agarose-gel electrophoresis. The severity of apoptosis was expressed as the percentage of apoptotic myocyte nuclei and nonapoptotic myocardial nuclei. RESULTS: Myocardial blood flow of the anterior left ventricular wall was reduced from 1.00 +/- 0.18 to 0.66 +/- 0.21 ml/min per g (p < 0.01), with a severe reduction of anterior regional wall thickening from a mean (+/-SD) of 39 +/- 4% to 9 +/- 8% (p < 0.01). There was no myocardial infarction in five pigs and minimal patchy infarction of < or = 6% of the area at risk in eight pigs. Apoptotic myocytes were observed in the hibernating myocardial region in all pigs (4.8 +/- 2.3%). Myocyte apoptosis was patchy in distribution and was found predominantly in the subendocardial myocardium (9.8 +/- 4.6%) and rarely in the subepicardial myocardium (0.32 +/- 0.45%). Apoptosis was found not only around focal fibrosis areas, but also in areas without fibrosis or patchy infarction. Apoptosis was found not only in 24-h hypoperfused myocardium, but also in 4-week hypoperfused myocardium. The severity of myocyte apoptosis correlated significantly with regional coronary blood flow reduction (r = 0.75, p < 0.01). No apoptosis was found in the normal control region. CONCLUSIONS: This study demonstrates that there is ongoing myocyte death through myocyte apoptosis in hypoperfused hibernating myocardium.

Abciximab in primary coronary angioplasty for acute myocardial infarction improves short- and medium-term outcomes.

OBJECTIVES: The purpose of this study was to compare the outcome of primary percutaneous transluminal coronary angioplasty for acute myocardial infarction (MI) when performed with or without the platelet glycoprotein IIb/IIIa antibody, abciximab. BACKGROUND: Abciximab improves the outcome of angioplasty but the effect of abciximab in primary angioplasty has not been investigated. METHODS: Data were collected from a computerized database. Follow-up was by telephone or review of outpatient or hospital readmission records. RESULTS: A total of 182 consecutive patients were included; 103 received abciximab and 79 did not. The procedural success rate was 95% in the two groups. At 30-day follow-up, the composite event rate of unstable angina, reinfarction, target vessel revascularization and death from all causes was 13.5% in the group of patients who did not receive abciximab, 4% (p < 0.05) in the abciximab group and 2.4% (p < 0.05) in the subgroup of patients (n = 87) who completed the 12-h abciximab infusion. At the end of follow-up (mean 7+/-4 months), the composite event rate was 32.4%, 17% (p < 0.05) and 13.1% (p < 0.01) in these three categories respectively. Abciximab bolus followed by a 12-h infusion was an independent predictor of event-free survival, in a Cox proportional hazards model (relative risk 0.49; 95% confidence interval 0.24 to 0.99; p < 0.05). CONCLUSIONS: Abciximab given at the time of primary angioplasty may improve the short- and medium-term outcome of patients with acute MI, especially when a 12-h infusion is completed.

Restenosis and progression of coronary atherosclerosis after coronary angioplasty.

The relation between restenosis and progression of atherosclerosis in other coronary segments after angioplasty was studied in 98 consecutive patients with 110 coronary stenoses successfully treated with angioplasty. At early angiographic restudy (5 +/- 2 months after angioplasty) 37 patients (38%) had restenosis (defined as a stenosis greater than or equal to 50% of the luminal diameter or loss of greater than or equal to 50% of the gain achieved by angioplasty); progression of atherosclerosis was observed in 4 patients with and 7 without restenosis (13 versus 11%, p = NS). Ninety of the 98 patients underwent a late angiographic restudy a mean of 34 +/- 11 months after angioplasty. Late restenosis was found in one patient. Progression of coronary artery disease (defined as a greater than or equal to 20% decrease in the diameter of a vessel initially narrowed by greater than or equal to 50% or a greater than or equal to 30% decrease when the initial stenosis was less than 50%) was examined in relation to restenosis in 85 of the 90 patients. It occurred in 9 of 27 patients with and 22 of 58 patients without restenosis (33 versus 38%, p = NS). Restenosis developed more rapidly than did progression of disease. Diameter stenosis increased from 35 +/- 8 to 73 +/- 11% at the early restudy in lesions with restenosis; in lesions with disease progression it increased from 9 +/- 18 to 20 +/- 28% (p less than 0.001) at the early restudy to 53 +/- 21% (p less than 0.001) at the late restudy.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple coronary angioplasty: a model to discriminate systemic and procedural factors related to restenosis.

To assess the interrelation of clinical and procedural factors responsible for restenosis, 119 patients undergoing coronary arteriography were studied a mean of 5.8 +/- 3 months after successful multiple percutaneous transluminal coronary angioplasty. In all clinical, angiographic and procedural variables, the 119 patients undergoing repeat catheterization were similar to the 87 patients that did not. Overall, restenosis occurred in 74 (34%) of 215 lesions. Sixty-three patients had no restenosis, 44 had at least one restenosis and 12 had restenosis at all angioplasty sites. The statistical distribution of restenoses did not follow a binomial model, suggesting that restenosis is more than a lesion-specific phenomenon. Of all the clinical and procedural variables assessed by multivariate logistic regression analysis, only percent stenosis before angioplasty (p less than 0.01), diabetes mellitus (p less than 0.01) and percent stenosis after angioplasty (p less than 0.05) were predictive of restenosis in the entire group. Patients with no restenosis and patients with restenosis at all sites were not different with respect to procedural variables; however, patients with restenosis at all sites more often (p less than 0.05) had diabetes and recent onset angina. In contrast, patients with no restenosis differed from patients with isolated restenosis with respect to procedural variables: severity of stenosis before and after angioplasty, balloon/artery lumen ratio and maximal inflation pressure. Thus, procedural factors may be more related to isolated restenosis, but patient-related factors such as diabetes and recent onset angina may play a more important role in patients with multiple restenoses.

Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men.

The effects of estrogen on cardiovascular risk factors have been less well defined in men than in women. We measured lipid and lipoprotein concentrations, lipoprotein particle size distributions, lipoprotein (a), homocysteine, and markers of thrombosis and fibrinolysis in 18 [corrected] healthy elderly men (age 74 +/- 3 years, mean +/- S.D.) before and after 9 weeks of treatment with 0.5, 1 or 2 mg/day of oral micronized 17beta-estradiol. LDL-C (-6%), apo B (-9%), triglyceride (-5%), and homocysteine (-11%) concentrations decreased with estradiol, whereas HDL-C (+14%) increased. Intermediate-size VLDL subclass concentrations were lowered and LDL and HDL subclass levels altered in such a way as to cause average LDL and HDL particle size to increase. Lipoprotein (a) did not change. Fibrinogen (-13%) and plasminogen activator inhibitor-1 (PAI-1) concentrations (-26%) decreased, but there were no changes in thrombotic markers including thrombin-antithrombin III complex, prothrombin fragment 1.2, D-dimer, antithrombin activity, protein-C and S and von Willebrand factor antigen. Breast tenderness occurred in four men and heartburn in five but did not require discontinuation of treatment. We conclude that oral estrogen in men reduces homocysteine, fibrinogen, and PAI-1 concentrations and favorably influences VLDL, LDL and HDL subclass levels without increasing markers of thrombotic risk.

Hospital treatment of congestive heart failure. Management according to hemodynamic profile.

Selection of therapy for subjects with acute congestive dardiac failure usually involves a choice among a diuretic, a vasodilator and an inotropic agent. Three principal questions are involved in the decision: (1) Is cardiac out normal or depressed? (2) Is blood pressure normal or depressed? (3) is regional myocardial ischemia present? Diuretics are safe and easy to administer, but they do not increase cardiac output or relieve hypoperfusion. Inotropic agents increase cardiac output but differ widely in their effects on blood pressure: selection of specific agents is influenced by their blood pressure effect. All inotropic agents, however, potentially aggravate regional myocardial ischemia. In ischemic heart failure, therefore, vasodilators which also increase cardiac output, may be chosen. Vasodilator administration is in turn limited by the decrease in arterial pressure which accompanies increasing infusion rate. When these three questions are considered in combination, an effective therapeutic regimen can be identified. Thus, congestion without hypoperfusion requires a diuretic if blood pressure is normal; and a vasodilator when blood pressure is increased. In the presence of congestion with hypoperfusion, a vasodilator is employed if blood pressure is normal; and a positive inotropic drug when blood pressure is depressed.

Early pharmacologic intervention and plaque stability in acute coronary syndromes.

Remarkable therapeutic advances in the treatment of acute coronary syndromes (ACS) have been made with antiplatelet and antithrombotic therapy. However, these therapies alone do not appear to completely stabilize culprit lesions. Evidence from a variety of sources suggests that intensive cholesterol lowering with statins favorably influences culprit lesion stabilization in patients with ACS. Potential mechanisms of benefit include improvements in endothelial function, decreased propensity for platelet thrombus formation, and reduction in inflammation at the site of the lesion. The Myocardial Ischemia with Aggressive Cholesterol Lowering (MIRACL) study is the first large-scale clinical trial to examine whether these mechanisms translate into clinical-event reduction in patients with ACS as well as the substantial proved benefits in the chronic coronary syndromes. In this trial, early initiation of atorvastatin after an episode of unstable angina or non-Q-wave myocardial infarction reduced events over the ensuing 16 weeks. It is hoped that a growing awareness of the benefits of early statin therapy to stabilize culprit lesions in ACS will lead to an increase in the proportion of coronary patients who will receive this beneficial therapy.

Are we aggressive enough in lowering cholesterol?

To date, 5 major randomized, placebo-controlled statin trials--the Scandinavian Simvastatin Survival Study, West of Scotland Coronary Prevention Study, Cholesterol and Recurrent Events trial, Long-term Intervention with Pravastatin in Ischaemic Disease, and Air Force/Texas Coronary Atherosclerosis Prevention Study--have convincingly shown that total mortality and major coronary events can be significantly reduced by lowering levels of low-density lipoprotein cholesterol (LDL-C) with statin therapy. These results were achieved in a broad range of patients including those with and without a history of coronary artery disease and with elevated or average LDL-C levels. The results also support the large body of epidemiologic evidence demonstrating that the lower the cholesterol level, the lower the cardiovascular risk. Evidence now substantially supports the urgency of physicians to aggressively target the lowering of LDL-C levels for the primary and secondary prevention of coronary disease.