Haemophilia and ageing.

Men with haemophilia have not only the challenges of living with HIV and/or HCV infection and premature arthritis as complications of their disorder, but they also confront the other ails of ageing. These include genitourinary problems such as prostatic hypertrophy, prostatic cancer and renal stone disease, and arterial disease for which haemophilia is not protective. Progressive arthritis and declining fitness may lead to loss of independence which causes great concern. Associated with the physical aspects of ageing, many patients also suffer from psychological symptoms which may be precipitated by changes in work such as early retirement and altered family dynamics. Many older men with haemophilia may never have consulted primary care physicians because of the rarity and complexity of their disorder. Haemophilia centre staff often assume responsibility for the identification and management of all health problems of their patients. Even when other clinicians are involved, patients require their centre's involvement in the investigation and support of many procedures such as coronary artery surgery and urological surgery. This paper addresses falls in the older man with haemophilia, their causes and consequences and cardiovascular problems in particular. Very little literature has been published about these common problems. We need to be aware of the ageing issues in haemophilia and develop 'wellness' programs which are directed to the early identification of disease as well as preventative strategies to reduce the physical and psychological impacts of ageing.

Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril.

BACKGROUND: Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. METHODS AND RESULTS: In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336 patients in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had regression/prevention of LVH (P=0.007). The effect of ramipril on LVH was independent of blood pressure changes. Patients who had regression/prevention of LVH had a lower risk of the predefined primary outcome (cardiovascular death, myocardial infarction, or stroke) compared with those who had development/persistence of LVH (12.3% versus 15.8%, P=0.006) and of congestive heart failure (9.3% versus 15.4%, P<0.0001). CONCLUSIONS: The ACE inhibitor ramipril decreases the development and causes regression of ECG-LVH independent of blood pressure reduction, and these changes are associated with reduced risk of death, myocardial infarction, stroke, and congestive heart failure.

VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. METHODS AND RESULTS: We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL-apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P:=0.04), apoCIII in VLDL+LDL (RR 2.3, P:=0.04), and apoE in HDL (RR 1.8, P:=0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P:=0.03), was not related to coronary events (RR 1.3, P:=0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. CONCLUSIONS: The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.

Reactivation of coagulation after stopping infusions of recombinant hirudin and unfractionated heparin in unstable angina and myocardial infarction without ST elevation: results of a randomized trial. OASIS Pilot Study Investigators. Organization to Assess Strategies for Ischemic++ Syndromes.

AIMS: To compare effects of heparin and hirudin on biochemical markers of coagulation. METHODS AND RESULTS: Patients (n=395) with unstable angina or myocardial infarction without ST elevation were randomized to a 72-h infusion of one of three regimens: unfractionated heparin (bolus of 5000 IU followed by an infusion of 1200 IU. h(-1)), low-dose hirudin (HBW 023; 0.2 mg. kg(-1)bolus followed by 0.10 mg. kg(-1). h(-1)) or medium-dose hirudin (0.4 mg. kg(-1)bolus followed by 0.15 mg. kg(-1). h(-1)). Infusions were adjusted to maintain an activated partial thromboplastin time of between 60-100 s. Activated partial thromboplastin time, prothrombin fragment 1.2 (F1.2), thrombin antithrombin III complex and D-dimer were measured before, during and after the infusion. Median activated partial thromboplastin time was similar in the two groups early on, but was significantly lower in the heparin group than in the combined hirudin group 48 h after starting the infusion (53 s and 75 s, respectively;P<0.001), and 6 h after stopping (31 s and 46 s, respectively;P<0.001). Median F1.2 levels were not significantly different between the groups during the infusion. Median thrombin antithrombin III levels in the heparin and hirudin groups were 2.8 microg. l(-1)and 2.3 microg. l(-1), respectively, at 6 h (P<0.001), and 3.0 microg. l(-1)and 2.3 microg. l(-1), respectively, at 48 h (P<0.001). Median D-dimer levels were 320 ng. ml(-1)and 260 ng. ml(-1)48 h after starting the infusion in the heparin and hirudin groups, respectively (P<0.001), and 415 ng. ml(-1)and 280 ng. ml(-1), respectively (P<0.001) 6 h after stopping. D-dimer levels were significantly elevated above baseline values in both groups 24-48 h after stopping the infusions. CONCLUSIONS: The greater reduction of thrombin antithrombin III and D-dimer during the hirudin infusion supports the hypothesis that hirudin is a more potent antithrombin agent than heparin. Increased D-dimer levels after stopping heparin or hirudin suggest that there is an ongoing pro-coagulant state. These results point to the greater efficacy of hirudin in preventing early clinical events (death, myocardial infarction and refractory ischaemia) compared with heparin that have been observed in large randomized trials. Persistent activation of coagulation afterstopping infusions in our study suggests that a longer course of antithrombotic treatment may be needed to pacify the thrombus.

Influence of baseline lipids on effectiveness of pravastatin in the CARE Trial. Cholesterol And Recurrent Events.

OBJECTIVES: We sought to assess the influence of baseline lipid levels on coronary event rates and the effectiveness of pravastatin therapy in the Cholesterol And Recurrent Events (CARE) study. BACKGROUND: The CARE study cohort provided a relatively unique opportunity to examine the relation between lipid levels and clinical events in a post-myocardial infarction (MI) population with relatively low cholesterol and low density lipoprotein (LDL) cholesterol values. METHODS: There were 4,159 patients with a previous infarct and a total cholesterol level <240 mg/dl, LDL cholesterol level 115 to 174 mg/dl and triglyceride level <350 mg/dl randomly allocated to placebo (n=2,078) or pravastatin 40 mg/day (n=2,081). Time to either coronary death or nonfatal MI (primary end point) or to the secondary end point, which included undergoing a coronary revascularization procedure, was determined as a function of baseline lipids (total, LDL, high density lipoprotein [HDL] cholesterol and triglyceride levels). RESULTS: Quartile analysis indicated important effects for LDL cholesterol, in which a higher LDL was associated with greater cardiac event rates (in the placebo group, every 25-mg/dl increment in LDL was associated with a 28% increased risk [5% to 56%, p=0.015]) in the primary event. The differential event rates with respect to baseline LDL cholesterol for placebo and pravastatin groups reduced the difference in clinical outcomes at lower LDL cholesterol levels. In both the placebo and pravastatin groups, an inverse relation between baseline HDL cholesterol and cardiac events was observed (10 mg/dl lower baseline HDL cholesterol level was associated with a 10% [0% to 19%, p=0.046] increase in coronary death or nonfatal MI). CONCLUSIONS: Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.

Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial.

BACKGROUND: We quantified cardiovascular death and/or left ventricular (LV) dilatation in patients from the SAVE trial to determine whether dilatation continued beyond 1 year, whether ACE inhibitor therapy attenuated late LV dilatation, and whether any baseline descriptors predicted late dilatation. METHODS AND RESULTS: Two-dimensional echocardiograms were obtained in 512 patients at 11+/-3 days and 1 and 2 years postinfarction to assess LV size, percentage of the LV that was akinetic/dyskinetic (%AD), and LV shape index. LV function was assessed by radionuclide ejection fraction. Two hundred sixty-three patients (51.4%) sustained cardiovascular death and/or LV diastolic dilatation; 279 (54.5%) had cardiovascular death and/or systolic dilatation. In 373 patients with serial echocardiograms, LV end-diastolic and end-systolic sizes increased progressively from baseline to 2 years (both P<.01). More patients with LV dilatation had a decrease in ejection fraction: 24.8% versus 6.8% (P<.001) (diastole) and 25.7% versus 5.3% (P<.001) (systole). Captopril attenuated diastolic LV dilatation at 2 years (P=.048), but this effect was carried over from the first year of therapy because changes in LV size with captopril beyond 1 year were similar to those with placebo. Predictors of cardiovascular death and/or dilatation were age (P=.023), prior infarction (P<.001), lower ejection fraction (P<.001), angina (P=.007), heart failure (P=.002), LV size (P<.001), and infarct size (%AD) (P<.001). CONCLUSIONS: Cardiovascular death and/or LV dilatation occurred in >50% of patients by 2 years. LV dilatation is progressive, associated with chamber distortion and deteriorating function that is unaffected by captopril beyond 1 year.

Risk stratification after myocardial infarction using signal-averaged electrocardiographic criteria adjusted for sex, age, and myocardial infarction location.

BACKGROUND: The objectives were to investigate the factors influencing signal-averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and to develop criteria for predicting arrhythmic events (AEs) that account for these factors. METHODS AND RESULTS: SAECGs were recorded 5 to 15 days after MI in 2461 patients without bundle-branch block. The duration (QRSd), terminal potential (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During follow-up (17 +/- 8 months), AEs (arrhythmic death; ventricular tachycardia, VT; ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating characteristic curves showed that QRSd discriminated patients with all types of AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also discriminated AE patients. Sex, age, and MI location significantly affected the SAECG; survivors without VT or VF were divided into subgroups (2 sex x 4 age x 2 MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall sensitivity and specificity but with less uniform values for each subgroup. A Cox model was constructed by use of multiple prognostic indicators, and in rank order, QRSd, previous MI, and Killip class were predictive of AEs. CONCLUSIONS: SAECG adjustments for sex, age, and MI location did not improve sensitivity and specificity but produced a more uniform predictive performance. The proposed criteria are based only on QRSd, because late potentials (VRMS and LAS) did not discriminate patients with sudden death. Duration of high-level activity during QRS (QRSd-LAS) can predict AEs, suggesting that the arrhythmogenic substate involves a large mass of myocardium.

Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE Investigators.

OBJECTIVES: This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients. BACKGROUND: Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors. METHODS: We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates. RESULTS: After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge. CONCLUSIONS: The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.

Myocardial infarction patients in the 1990s--their risk factors, stratification and survival in Canada: the Canadian Assessment of Myocardial Infarction (CAMI) Study.

OBJECTIVES: This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND: The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS: All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS: The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS: One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

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.

The antianginal efficacy of isosorbide dinitrate therapy is maintained during diuretic treatment.

OBJECTIVES: To determine whether the use of a diuretic would maintain the antianginal efficacy of isosorbide dinitrate during 1 week of therapy. METHODS: During continuous therapy, organic nitrates have a reduction in antianginal effectiveness and cause fluid retention. The study was a randomized, double-blind, placebo-controlled crossover design examining the effect of 1 week of daily treatment with 50 mg hydrochlorothiazide/5 mg amiloride on the antianginal effectiveness of 30 mg isosorbide dinitrate administered every 6 hours. Exercise stress testing was performed before and 3 hours after administration of isosorbide dinitrate at the start and end of the placebo and diuretic treatment phases. RESULTS: The time to onset of angina (475 +/- 35 versus 490 +/- 29 seconds, difference not significant) and to moderate angina after administration of isosorbide dinitrate (542 +/- 40 versus 566 +/- 37 seconds, difference not significant) were similar at the start and end of the diuretic phase of the study but were reduced at the end of the placebo phase (471 +/- 40 versus 410 +/- 40 seconds, p < 0.05 and 531 +/- 38 versus 466 +/- 39 seconds, p < 0.05, respectively). Total exercise time and time to onset of angina 3 hours after administration of isosorbide dinitrate were longer (p < 0.005) at the end of the diuretic phase compared with the end of the placebo phase. Patients gained weight during the placebo phase and lost weight during the diuretic phase of the study. The change in weight was inversely correlated to the change in total exercise time (r = -0.53, p < 0.05). CONCLUSIONS: Patients using a diuretic with isosorbide dinitrate maintain an increased anginal threshold and total exercise time compared with placebo. Weight change is inversely related to exercise duration, and this result is consistent with fluid retention restoring cardiac preload during nitrate use. The increased anginal threshold during concurrent isosorbide dinitrate and diuretic use may be attributable to maintenance of the organic nitrate-induced reductions in cardiac preload.

N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction.

BACKGROUND: Atrial natriuretic factor (ANF) is a peptide hormone secreted from cardiac atria in response to increased atrial pressure. Because of a longer half-life and greater stability, the N-terminal of ANF prohormone (N-terminal proANF) may be a better integrator of atrial peptide secretion than ANF itself. After myocardial infarction, elevation of ANF and other neurohormones has been associated with a poor prognosis. However, when left ventricular ejection fraction (LVEF) and other important clinical variables are included in multivariate analysis, the independent predictive value of these neurohormones has been reduced markedly. METHODS AND RESULTS: To test the prognostic value of N-terminal proANF after myocardial infarction, its plasma concentration was measured a mean of 12 days after infarction in 246 patients in the Survival and Ventricular Enlargement (SAVE) Study. N-terminal proANF was a much stronger predictor of survival than ANF itself. Furthermore, in multivariate analysis of cardiovascular mortality and development of heart failure, N-terminal proANF in contrast to ANF and other neurohormones was still a powerful and independent predictor when the model included age, gender, prior myocardial infarction, hypertension, diabetes, use of thrombolysis, Killip class, infarct location, and LVEF. CONCLUSIONS: The measurement of N-terminal proANF supplements presently used clinical and objective assessments and provides an important independent predictor of prognosis with respect to cardiovascular mortality and development of heart failure.

Quality of life among patients post-myocardial infarction at baseline in the Survival and Ventricular Enlargement (SAVE) trial.

A quality of life ancillary study was incorporated into the Survival and Ventricular Enlargement (SAVE) trial of captopril versus placebo among patients who survived an acute myocardial infarction with compromised ventricular functioning, but no overt heart failure. Assessments included patient symptoms, health perceptions, emotional, cognitive, social and sexual levels of functioning, as well as potential covariates, such as life events and social support. The purpose of this study was to evaluate the psychometric properties of the quality of life measures in the SAVE at baseline, and provide a pre-randomization profile of the SAVE patients. One hundred and eighty-four patients participated in this aspect of the trial. Reliability alpha coefficients were adequate or better for all questionnaires, except for life events and sexual activities. Consistent with prior studies, the quality of life parameters were uncorrelated with ventricular ejection fraction. Despite experiencing a recent myocardial infarction with compromised ventricular functioning, patients at baseline generally neither appeared depressed nor focused on symptoms. The baseline findings support the inclusion of the quality of life ancillary study in the overall SAVE trial because of the independent contribution likely to be achieved in terms of evaluating both disease progression and treatment efficacy.

Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril.

BACKGROUND: Left ventricular enlargement after myocardial infarction increases the likelihood of an adverse outcome. In an echocardiographic substudy of the Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril would attenuate progressive left ventricular enlargement in patients with left ventricular dysfunction after acute myocardial infarction and, if so, whether this would be associated with improved clinical outcome. METHODS AND RESULTS: Two-dimensional transthoracic echocardiograms were obtained in 512 patients at a mean of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420 survivors. Left ventricular size was assessed as left ventricular cavity areas at end diastole and end systole and left ventricular function as percent change in cavity area from end diastole to end systole. Patients were randomly assigned to placebo or captopril, and the incidence of adverse cardiovascular events consisting of cardiovascular death, heart failure requiring either hospitalization or open-label angiotensin-converting enzyme inhibitor therapy, and recurrent infarction were determined over a follow-up period averaging 3.0 +/- 0.6 years. Irrespective of treatment assignment, baseline left ventricular systolic area and percent change in area were strong predictors of cardiovascular mortality and adverse cardiovascular events. At 1 year, left ventricular end-diastolic and end-systolic areas were larger in the placebo than in the captopril group (P = .038, P = .015, respectively), and percent change in cavity area was greater in the captopril group (P = .005). One hundred eleven of the 420 1-year survivors with 1-year echo measurements (26.4%) experienced a major adverse cardiovascular event, and these patients had more than a threefold greater increase in left ventricular cavity areas than those with an uncomplicated course. Sixty-nine patients with adverse cardiovascular events were in the placebo group compared with 42 patients in the captopril-treated group (a risk reduction of 35%, P = .010). CONCLUSIONS: Two-dimensional echocardiography provides important and independent prognostic information in patients after infarction. Left ventricular enlargement and function after infarction are associated with the development of adverse cardiac events. Attenuation of ventricular enlargement with captopril in these patients was associated with a reduction in adverse events. This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome.

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.

LDL molecular size as risk factor in coronary artery disease.

Sera of 65 fasting human subjects--32 patients with coronary artery disease (CAD) aged 42-80 years and 33 healthy individuals--were tested for determination of nine lipid-related laboratory parameters, including protein-enriched LDL (low density lipoprotein cholesterol (LDL apo B) which is proportional to the amount of cholesterol per LDL particle. Three of the investigated parameters: protein-enriched LDL, HDL cholesterol and apo B level differed significantly in the two groups (corrected P < 0.001, P < 0.009 and P < 0.009, respectively). Discriminant analysis revealed that protein-enriched LDL, LDL cholesterol, apo B and fasting triglyceride levels, but not HDL cholesterol, were the major discriminating factors for CAD in this study. Pearson correlation coefficients were calculated to describe the association between this size-related parameter and those which in both groups seem to be most strongly associated with it: apo B/A-I ratio (i), triglyceride (ii) and LDL/HDL ratio (iii). The analysis was done separately in the two groups. In the patients with CAD the influence of these three parameters were less decisive in the determination of the protein-enriched LDL than in the controls (corr. coeff.: (i) -0.155 vs -0.358; (ii) -0.624 vs -0.791; (iii) -0163 vs -0.471). In healthy volunteers the size-reducing effect of the same parameters was more profound, and at high values of LDL/HDL ratio, apo B/apo A-I ratio and triglyceride no distinction in LDL particle size can be made any longer between CAD patients and controls. Thus the improvement of the atherogenic profile does not seem to result in the reduction of risk for CAD in terms of LDL size and composition.

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.

Right ventricular infarction: two-dimensional echocardiographic evaluation.

Seventeen patients with predominant right ventricular infarction (RVMI) were studied with two-dimensional echocardiography (2DE). On initial 2DE all had abnormal wall motion (AWM), defined as akinesis plus dyskinesis, in the inferior right ventricle (RV), inferior interventricular septum, and inferior left ventricle (LV). The extent of RV vs LV AWM in short-axis sections at mitral, chordal, and papillary levels was 58% vs 29%, 56% vs 38%, and 59% vs 38%, respectively. The calculated topographic extent of AWM was greater in the RV than in the LV (58% vs 36%, p less than 0.05), and the RV/LV ratio (1.65) exceeded (p less than 0.001) unity. Peak creatine phosphokinase levels correlated significantly (p less than 0.001) with the topographic extent of LV AWM (r = 0.79) or RV + LV AWM (r = 0.75). Although all patients had RV dilatation, eight also had LV dilatation. Serial studies detected the cause of mechanical complications (n = 13), mural echo densities suggesting thrombi (LV in six and RV in seven), and persistent AWM in survivors. Thus, 2DE provided diagnostic data, and assessment of RV and LV AWM confirmed predominant RV involvement.