A quicker method for calculating mortality ratios based on survival rates in clinical trials and other follow-up studies.

OBJECTIVES: To provide reference expected cumulative survival tables, reducing steps in the calculation of mortality ratios and excess death rates from the medical literature, when source data are in terms of survival curves or cumulative survival rates. METHOD: Actuarial methodology. RESULTS: Tables provide cumulative expected survival rates calculated by entry age and for different periods of follow-up, as used in clinical trials and registries in the medical literature. CONCLUSION: The observed survival in scientific papers can be appraised promptly using cumulative survival tables calculated from either insurance or population life tables.

Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.

BACKGROUND: We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome. METHODS: We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure. FINDINGS: Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included. INTERPRETATION: Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.

Metabolic syndrome X: a review.

Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.

Expected versus observed survival in 3 large population studies with HMG-CoA reductase inhibitors.

OBJECTIVE: HMG-CoA reductase inhibitors (statins) can lower low-density lipoprotein (LDL). We examined how they were used in three large recent population studies, shedding new light on the relationship between cholesterol levels and survival. METHODS: Mortality observed in the placebo and treated groups of these primary and secondary prevention studies using statins was compared with the expected mortality given in existing life tables. RESULTS: In the West of Scotland Coronary Prevention Study (WOSCOPS), 6595 men with no proven coronary disease but with high baseline cholesterol were given pravastatin or placebo for 5 years. The mortality ratio (MR) was 125% when the placebo group was compared with the Canadian Insurance Association (CIA) 1986--92 ultimate mortality table. Pravastatin abolished the increased risk associated with LDL cholesterol. In the Scandinavian Simvastatin Study (4S), 4444 patients with coronary disease and high baseline cholesterol were given simvastatin or placebo for 5 years. The placebo group had a MR of 200%, compared with CIA life tables. Simvastatin decreased this increased mortality to 153%. In the Cholesterol and Recurrent Events study (CARE), 4159 patients with previous myocardial infraction and near-normal cholesterol levels were given pravastatin or placebo for 5 years. In the placebo group, the MR was 200%, compared with the CIA life tables. In patients given pravastatin, mortality was only marginally reduced to 192%. CONCLUSIONS: In primary prevention, reducing serum cholesterol abolished the increased mortality associated with high cholesterol. In secondary prevention, lipid-lowering agents improved survival in the treated group, mainly if baseline cholesterol was high.

Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators.

Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril.

OBJECTIVES: This study attempted to evaluate whether neurohumoral activation at the time of hospital discharge in postinfarction patients helps to predict long-term prognosis and whether long-term therapy with the angiotensin-converting enzyme inhibitor captopril modifies this relation. BACKGROUND: Neurohumoral activation persists at the time of hospital discharge in a large number of postinfarction patients. The Survival and Ventricular Enlargement (SAVE) study demonstrated that the angiotensin-converting enzyme inhibitor captopril improves survival and decreases the development of severe heart failure in patients with left ventricular dysfunction (left ventricular ejection fraction < or = 40%) but no overt postinfarction heart failure. METHODS: In 534 patients in the SAVE study, plasma neurohormone levels were measured a mean of 12 days after infarction. Patients were then randomized to receive captopril or placebo and were followed up for a mean (+/- SD) of 38 +/- 6 months (range 24 to 55). The association between activation of plasma neurohormones at baseline and subsequent cardiovascular mortality or the development of heart failure was assessed with and without adjustment for other important prognostic factors. RESULTS: By univariate analysis, activation of plasma renin activity and aldosterone, norepinephrine, atrial natriuretic peptide and arginine vasopressin levels were related to subsequent cardiovascular events, whereas epinephrine and dopamine levels were not. By multivariate analysis, only plasma renin activity (relative risk 1.6, 95% confidence interval [CI] 1.0 to 2.5) and atrial natriuretic peptide (relative risk 2.2, 95% CI 1.3 to 3.8) were independently predictive of cardiovascular mortality, whereas the other neurohormones were not. Only plasma renin activity and aldosterone, atrial natriuretic peptide and arginine vasopressin were independent predictors of the combined end points of cardiovascular mortality, development of severe heart failure or recurrent myocardial infarction. Except for 1-year cardiovascular mortality, the use of captopril did not significantly modify these relations. CONCLUSIONS: Neurohumoral activation at the time of hospital discharge in postinfarction patients is an independent sign of poor prognosis. This is particularly true for plasma renin activity and atrial natriuretic peptide. Except for 1-year cardiovascular mortality, captopril does not significantly modify these relations.

Activation of neurohumoral systems in postinfarction left ventricular dysfunction.

OBJECTIVES: This study was conducted to evaluate the degree of neurohumoral activation around the time of hospital discharge after myocardial infarction. BACKGROUND: Because pharmacologic interventions that block the effects of neurohumoral activation improve the prognosis after infarction, we hypothesized that widespread neurohumoral activation persists in some patients until at least the time of hospital discharge and that the determinants of activation vary from one system to another. METHODS: Five hundred nineteen patients in the Survival and Ventricular Enlargement Study (SAVE) had plasma neurohormones measured before randomization at a mean of 12 days after infarction. All patients had left ventricular dysfunction (left ventricular ejection fraction < or = 40%) but no overt heart failure. RESULTS: Although all neurohormones except epinephrine were increased compared with values in age-matched control subjects, plasma norepinephrine (301 +/- 193 vs. 222 +/- 87 pg/ml, p < 0.001), renin activity (3.0 +/- 3.7 vs. 1.2 +/- 1.2 ng/ml per h, p < 0.001), arginine vasopressin (1.9 +/- 6.9 vs. 0.7 +/- 0.3 pg/ml, p < 0.001) and atrial natriuretic peptide (75 +/- 75 vs. 21 +/- 9 pg/ml, p < 0.001) values ranged from normal to very high, indicating a wide spectrum of neurohumoral activation. Activation of one system did not correlate with activation of another. The clinical and laboratory variables most closely associated with neurohumoral activation were Killip class, left ventricular ejection fraction, age and use of diuretic drugs. The association between neurohumoral activation and clinical and laboratory variables varied from one neurohormone to another. CONCLUSIONS: Neurohumoral activation occurs in a significant proportion of patients at the time of hospital discharge after infarction. Which neurohormone is activated and which clinical and laboratory variables determine this activation vary from one neurohormone to another.

Activation of neurohumoral systems following acute myocardial infarction.

Previous studies have indicated that patients with an acute myocardial infarction have marked activation of all neurohumoral systems on admission to the hospital. This activation begins to subside within the first 72 hours so that by 7-10 days, all plasma neurohormones have returned to normal. The only documented exceptions were found to occur in patients with left ventricular dysfunction and overt heart failure, where both plasma renin activity and atrial natriuretic peptide were increased, and in patients with left ventricular dysfunction but no overt heart failure, where only atrial natriuretic peptide was increased. Although these studies suggest that neurohumoral activation rarely occurs at the time of hospital discharge, they were small and may have missed an important subgroup of patients with persistent neurohumoral activation. In the Survival and Ventricular Enlargement (SAVE) study, 522 patients had plasma neurohumoral levels measured at a mean of 12 days postinfarction. All SAVE patients had left ventricular dysfunction (left ventricular ejection fraction less than or equal to 40%), but no overt heart failure. In this group of patients, all neurohumoral levels (plasma renin activity, norepinephrine, arginine vasopressin, and atrial natriuretic peptide) were found to be increased compared with age-matched control subjects. These results indicate that, in fact, a subgroup of patients without overt heart failure has persistent neurohumoral activation at the time of hospital discharge postinfarction, and that this activation involves several neurohumoral systems. Since patients with persistent neurohumoral activation postinfarction are likely those most at risk of developing complications and the ones most likely to benefit from pharmacologic interventions blunting the effects of neurohumoral activation, measurement of predischarge neurohumoral levels may be useful.

The role of coronary angioplasty in patients with associated noncardiac medical and surgical conditions.

Percutaneous transluminal coronary angioplasty was performed in 22 patients with associated significant medical or surgical conditions. It was successful in 22 patients. Two had procedure-related complications: one femoral hematoma and one small myocardial infarction. The patients were divided into a 'medical' group (12 patients) and a 'surgical' group (10 patients). In the medical group, mean coronary artery stenosis decreased from 87 +/- 5% to 20 +/- 13% and mean coronary artery stenosis decreased from 57 +/- 2% to 16 +/- 7%. In the surgical group coronary artery stenosis decreased from 83 +/- 9% to 18 +/- 9% and the gradient from 49 +/- 16 to 16 +/- 6 mmHg. Percutaneous transluminal coronary angioplasty allowed the safe management of underlying conditions in all patients so that medical treatment could be continued and noncardiac surgery performed.

Dipyridamole testing compared to exercise stress for thallium-201 imaging in patients with left bundle branch block.

Because of numerous reports of false positive results with thallium-201 (Tl-201) stress testing in patients with left bundle branch block, the authors decided to evaluate another mode of coronary vasodilatation, dipyridamole, for the diagnosis of coronary atheromatosis. Nine patients were prospectively studied with stress and dipyridamole Tl-201 scintigraphy; both tests were performed within three to 79 days of one another. Five of the patients also had coronary angiograms (four within one year, one five years earlier). Four of the patients had normal results with both tests (two normal angiograms, two not performed); two had reversible septal defects with stress-induced coronary vasodilatation but normal dipyridamole studies (only one had an angiogram, which was normal); one patient had a fully reversible septal defect with stress and a fixed defect with dipyridamole (normal angiogram); one had a partially reversible septal stress defect which was fixed with dipyridamole; and one had a normal stress study but a reversible septal defect with dipyridamole (an angiogram performed five years earlier showed 30 to 40% stenosis of the anterior descending artery). Because it seems that dipyridamole produces fewer false positive results, it should be used instead of stress testing to induce coronary vasodilatation in patients with left bundle branch block.

Efficacy of delayed percutaneous transluminal coronary angioplasty after intravenous use of streptokinase in myocardial infarction.

Between June 1984 and December 1986, 35 patients with acute myocardial infarction received streptokinase intravenously within 3 hours after the beginning of chest pain and underwent percutaneous transluminal coronary angioplasty (PTCA) either immediately (in 2 cases) or 1 to 19 (mean 4.4) days later (in 33). The rate of successful PTCA was 89%. Reocclusion occurred in one patient. The mean percentage of stenosis decreased from 86% to 11%. The mean trans-stenotic gradient was reduced from 41 to 11 mm Hg. The results suggest that in patients whose condition is stable, PTCA performed a few days after thrombolysis is a valuable alternative to more aggressive treatment with immediate PTCA.

Systemic and regional blood flows during graded treadmill exercise in dogs.

The purpose of the study was to describe hemodynamic response and regional blood flows through various organs and tissues (microsphere technique) in dogs (n = 8), at rest and during mild (4 km/h, 13% slope; heart rate = 154 bpm), moderate (4 km/h, 26% slope; heart rate = 201 bpm), and severe (4 km/h, 39% slope; heart rate = 266 bpm) exercise on treadmill. Cardiac output (rest: 3.2 +/- 0.3; 39% slope: 10.2 +/- 1.3 l/min; mean +/- SE), systolic aortic pressure (rest: 122 +/- 4; 39% slope: 158 +/- 9 mm Hg), and left atrial pressure (rest: 5 +/- 0.7; 39% slope: 11.0 +/- 0.6 mm Hg) increased linearly with workload. On the contrary stroke volume increased from rest (35 +/- 2 ml) to mild (38 +/- 2 ml) and moderate (42 +/- 3 ml) exercise but decreased in response to the severe workload (38 +/- 5 ml). Regional blood flows across the brain, femoral bone, adrenal glands and temporalis muscle were not modified during exercise. On the contrary, a marked increase in regional blood flow was observed through the flexor and extensor muscles of the limb (X 5 to X 15), the muscles of the back (X 4) and the diaphragm (X 2.5). The small inconsistent increase in nutritional tongue blood flow probably underestimated the increased perfusion through arteriovenous shunts in the mucosa for heat-loss purposes. Myocardial blood flow increased in a linear fashion with work load in both ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarction diagnosis with body surface potential mapping, electrocardiography, vectorcardiography and thallium-201 scintigraphy: a correlative study with left ventriculography.

In 35 subjects with typical or atypical angina and/or documented myocardial infarction (MI), body surface potential maps (BSPMs), ECG, VCG and rest Thallium-201 (T1-201) have been compared to left ventriculography (LVG). BSPMs were recorded with 26 ECGs, and BSPM abnormalities for MI cases were considered to be areas of normally positive potentials that have become negative. Subjects with MI were classified according to the segmental localization and degree of asynergy on LVG. Moderate anterolateral and apical asynergy were found to correlate with BSPM diagnosis of anterolateral MI and ischemia, severe anterolateral and apical asynergy with BSPM diagnosis of anterolateral MI and ischemia, and moderate diaphragmatic and/or posterobasal asynergy with BSPM diagnosis of posterior MI. Simultaneous anterior and posterior asynergy were found for BSPM diagnosis of anterior with posterior MI. Subjects with no LVG asynergy had normal BSPMs. BSPM diagnosis had the highest correlation coefficient with the LVG diagnosis (r = 0.88). ECG and VCG showed similar results with r = 0.65 and 0.71 respectively, while T1-201 had r = 0.55. The examination of our BSPMs, as well as the ECG, VCG and T1-201, did not permit to detect apical damage in presence of anterior MI, and posterobasal damage in the presence of inferoposterior MI. It is concluded that BSPMs are slightly superior to ECG and VCG for diagnosis of MI.

Role of autoregulation in spatial and temporal perfusion heterogeneity of canine myocardium.

Spatial heterogeneity, the region-to-region variation in flow at an instant, and temporal heterogeneity, the time variation of flow in a small region of myocardium, were investigated with radioactive labeled microspheres in 111 regions of left ventricular myocardium. The error of the method was measured by simultaneously injecting four differently labeled microspheres (15 +/- 5 (SD) micron). The coefficient of variation (CV) was 6.5 +/- 1.0%. Spatial variation with autoregulation intact was 21.7 +/- 1.4% (CV); with autoregulation abolished and low perfusion pressure, it was 34.3 +/- 3.7%; and with normal perfusion pressure, 30.8 +/- 6.4% (differences not significantly). This degree of variation was similar in the entire left ventricle and its layers. Forces which tended to cause vessel closure (low perfusion pressure, ventricular systolic pressure, and ventricular diastolic pressure) tended to increase CV. Temporal heterogeneity as measured by 20-s intervals between microsphere injections was 11.1 +/- 1.0% (CV) with autoregulation, 9.8 +/- 1.3% (P less than 0.05) with autoregulation abolished, and 8.4 +/- 0.8% (P less than 0.05) when perfusion pressure was restored. A periodicity of flow cycles of 30-90 s was suggested by the data. These results suggest that spatial heterogeneity is less influenced by autoregulation than by hydraulic considerations, whereas temporal heterogeneity is a component of autoregulation.