Inflammation and cardiovascular events in individuals with and without chronic kidney disease.

Inflammation and chronic kidney disease predict cardiovascular events. Here we evaluated markers of inflammation including fibrinogen, albumin and white blood cell count in individuals with and without stages 3-4 chronic kidney disease to assess inflammation as a risk factor for adverse events, the synergy between inflammation and chronic kidney disease, and the prognostic ability of these inflammatory markers relative to that of C-reactive protein. Using Atherosclerosis Risk in Communities and Cardiovascular Health Study data, inflammation was defined by worst quartile of at least 2 of these 3 markers. In Cox regression models, inflammation was assessed as a risk factor for a composite of cardiac events, stroke and mortality as well as components of this composite. Among 20 413 patients, inflammation was identified in 3594 and chronic kidney disease in 1649. In multivariable analyses, both inflammation and chronic kidney disease predicted all outcomes, but their interaction was non-significant. In 5597 patients with C-reactive protein levels, inflammation and elevated C-reactive protein had similar hazard ratios. When focusing only on individuals with the worst quartile of white cell count and albumin, results remained consistent.

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

OBJECTIVES: We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. METHODS: We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. RESULTS: Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. CONCLUSIONS: Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

Cause and management of heart failure in patients with chronic renal disease.

Heart failure occurs in 40% of patients with end-stage renal disease and is a major determinant of mortality. Heart failure occurs in patients with left ventricular systolic dysfunction (dilated left ventricle) as well as those with a normal resting ejection fraction (nondilated left ventricle). This report describes the cause of heart failure among patients with end-stage renal disease and the effect of heart failure on survival. We also discuss the impact of renal failure on the medical management of these patients.

Antithrombotic therapy for prosthetic valves: routine treatment and special considerations.

The use of prosthetic heart valves has increased over the past 3 decades. Antithrombotic agents remain the mainstay of therapy to prevent thromboembolic events caused by the presence of a prosthetic heart valve. We examine the risks of thromboembolic events as well as the risks and benefits of antithrombotic therapy in patients with mechanical and bioprosthetic heart valves. We also review the data regarding the use of antithrombotic therapy in special groups of patients, such as those with intracranial bleeding, pregnant women with prosthetic heart valves, and patients with prosthetic heart valves undergoing surgery.

Antithrombotic therapy for valve disease: native and prosthetic valves.

The use of antithrombotic agents to prevent thromboembolic events in patients with valvular heart disease is common. Recent studies using improved diagnostic techniques have allowed better elucidation of valvular abnormalities and re-evaluated the incidence and risk of thromboembolism. We review the recent literature examining the risk of thromboembolic events in various valvular abnormalities, and the use of different antithrombotic agents in the prevention of thromboembolic events. We also review the current recommended practice in both native valve abnormalities and prosthetic heart valves.

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.

Warfarin anticoagulation and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction.

OBJECTIVES: We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction. BACKGROUND: Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial. METHODS: We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome. RESULTS: On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology. CONCLUSIONS: In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.

The Angina-related Limitations at Work Questionnaire.

This report describes initial experience with a new self-report questionnaire, the 17 item Angina-related Limitations at Work Questionnaire. Forty employed individuals with chronic stable angina pectoris completed the questionnaire which retrospectively examined the subjects' difficulty in performing specific work activities during the preceding 4 week period. The questionnaire performed well in this study and there was initial evidence of its validity and reliability. More than one-half of the respondents (52.5%) indicated at least some difficulty in performing one or more of the 17 work items due to angina during the preceding 4 weeks, with the greatest difficulty experienced in physically exerting tasks, handling stressful situations and feeling a sense of accomplishment. In contrast, only one-quarter of the sample missed any work time. In tests of convergent validity, the degree of work limitation correlated significantly with SF-36 physical and mental health component scores and with self-reports of angina symptoms. The questionnaire had internal reliability, with item to total score correlations of 0.75 or higher for 14 of the 17 items. In summary, the Angina-related Limitations at Work Questionnaire offers promise for quantifying work limitations among individuals with chronic stable angina.

Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial.

OBJECTIVES: This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction. BACKGROUND: APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown. METHODS: We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome. RESULTS: APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users. CONCLUSIONS: In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Enhanced hepatic uptake of thallium-201 in patients with severe narrowing of the right coronary artery.

To assess the hepatic uptake of thallium-201 after exercise treadmill testing and to investigate whether hepatic uptake of thallium-201 may be a useful marker of right coronary artery (RCA) disease, 43 patients were studied: 17 with RCA disease (9 with 1-vessel disease, 8 with multivessel disease including the RCA), 8 with left coronary system disease alone, and 18 with a low probability (< 5%) of coronary disease. All subjects were studied with symptom-limited exercise and redistribution thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy. Two indexes of hepatic uptake were derived: a liver-to-heart ratio after stress, and a stress-to-rest hepatic ratio. The low-probability group had a liver/heart ratio of 0.48 +/- 0.02. In the group with RCA disease alone, liver/heart ratio was 1.29 +/- 0.20 (p < 0.005 vs low-probability group). Patients with multivessel coronary artery disease involving the RCA had a ratio of 1.19 +/- 0.16 (p < 0.005 vs low-probability group), and patients with only left coronary system disease had a liver/heart ratio of 0.87 +/- 0.15 (p < 0.05 vs low-probability group). The stress/rest ratio of the low-probability group was 0.83 +/- 0.04. Patients with RCA disease alone had a stress/rest ratio of 1.49 +/- 0.25 (p < 0.05 vs low-probability group), and patients with multivessel disease involving the RCA had a stress/rest ratio of 1.16 +/- 0.08 (p < 0.005 vs low-probability group).(ABSTRACT TRUNCATED AT 250 WORDS)

Familial lipoprotein disorders and premature coronary artery disease.

Significant risk factors for premature coronary heart disease include: (1) family history, (2) elevated low density lipoprotein (LDL) cholesterol level > or = 160 mg/dl, l, (3) decreased high density lipoprotein (HDL) cholesterol level < 35 mg/dl, l, (4) cigarette smoking, (5) high blood pressure and (6) diabetes mellitus. All of these risk factors are common in patients with premature heart disease. Common familial lipid disorders associated with premature heart disease include familial lipoprotein(a) excess, familial dyslipidemia (elevated triglycerides and decreased HDL cholesterol), familial combined hyperlipidemia (elevations of LDL cholesterol and triglycerides, and often decreased HDL cholesterol), familial hypoapobetalipoproteinemia (elevated apolipoprotein B levels), familial hypoalphalipoproteinemia (low HDL cholesterol levels), and familial hypercholesterolemia (elevated LDL cholesterol levels). All these disorders have been characterized using age and gender specific 90th and 10th percentile values from the normal population. The diagnosis and potential management of these disorders is reviewed.

Treatment of asymptomatic patients with left ventricular dysfunction.

Results of the SOLVD prevention trial and of the SAVE trial indicate that long-term treatment with ACE inhibitors in asymptomatic patients with LV systolic dysfunction prevents the progression to overt CHF and reduces hospitalizations for CHF. ACE inhibitors have been shown to reduce mortality in at least some subsets of asymptomatic patients with LV systolic dysfunction, notably those with recent myocardial infarction.

Utility of in vivo, intracardiac two-dimensional echocardiography in the assessment of myocardial risk area and myocardial dyssynergy during coronary occlusion and reperfusion.

We have previously reported the potential use of intracardiac echocardiography (ICE) in a variety of clinical settings, including detection of pericardial effusion, intracardiac masses, congenital cardiac defects, and during simulated balloon valvuloplasty. The utility of intracardiac ultrasound imaging of the left ventricle (LV) in patients with coronary disease needs to be further explored. We performed this study with the purpose of evaluating risk area and regional wall-motion abnormalities produced by ischemia using ICE. Ten episodes of ischemia were produced by transiently occluding the left anterior descending coronary artery in five dogs. ICE was performed with a modified 5-MHz transesophageal echocardiographic probe placed in the right atrium. Continuous short-axis images of the LV were obtained before, during, and after coronary occlusion. Risk area was defined using myocardial contrast echocardiography. In all cases, ICE provided high resolution images of the LV. Risk area and regional wall-motion abnormalities were readily detected. There was good correlation between the risk area (x) and extent of dyssynergy (y), defined by the equation y = 0.76x + 6.38 (r = 0.80, P less than 0.01). We conclude that ICE provides potentially useful information concerning regional LV dysfunction, and, when combined with myocardial contrast echocardiography, area at risk. This technique may be useful during interventional procedures once a catheter-based ultrasound transducer with adequate depth of field to provide images of the entire LV can be developed.

Direct angioplasty for acute myocardial infarction. A review of outcomes in clinical subsets.

PURPOSE: To review the usefulness of angioplasty done early in the course of an acute myocardial infarction without preceding thrombolytic therapy. DATA SOURCES: The English-language literature was searched from 1983 through October 1991 using MEDLINE; bibliographies from selected articles were searched by hand. STUDY SELECTION: Series reporting results for direct angioplasty without preceding thrombolytic therapy were reviewed. Twenty-three articles describing a total of 4368 patients were found. DATA EXTRACTION: After duplicate patient series were eliminated, weighted average short- and long-term mortality rates were calculated for the remaining 2073 patients in 10 series and for selected clinical subsets. RESULTS OF DATA SYNTHESIS: Average hospital mortality for patients with acute myocardial infarction having direct angioplasty was 8.3% (95% Cl, 7.1% to 9.5%). Patients in cardiogenic shock had the highest mortality (44.2%; Cl, 35.9% to 52.5%); patients with one-vessel disease had the lowest (1%; Cl, 0% to 2.3%). For patients in cardiogenic shock, data on direct angioplasty appeared superior to data for similar patients receiving thrombolytic therapy. Although few data exist, a survival advantage was also suggested for patients with a history of previous bypass surgery (hospital mortality, 11.1% [Cl, 4.4% to 17.8%]). CONCLUSIONS: Direct angioplasty has an overall mortality similar to that of thrombolytic therapy. Patients who may benefit more from mechanical revascularization than from thrombolytic therapy include those at increased risk for thrombolytic therapy (uncontrolled hypertension, recent major surgery, cerebrovascular accident, prolonged cardiopulmonary resuscitation, or bleeding diathesis), and those with cardiogenic shock. The efficacy in several other patient subsets (age greater than 65 years, previous coronary artery bypass grafting, prolonged delay before reperfusion) warrants further study.

Familial lipoprotein disorders in patients with premature coronary artery disease.

BACKGROUND: Genetic lipoprotein disorders have been associated with premature coronary artery disease (CAD). METHODS AND RESULTS: The prevalence of such disorders was determined in 102 kindreds (n = 603 subjects) in whom the proband had significant CAD documented by angiography before the age of 60 years. Fasting plasma cholesterol, triglyceride, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein (a) [Lp(a)] values above the 90th percentile and high density lipoprotein (HDL) cholesterol and apo A-I below the 10th percentile of age- and sex-specific norms were defined as abnormal. An abnormality was noted in 73.5% of probands compared with 38.2% in age-matched controls (p less than 0.001), with a low HDL cholesterol level (hypoalphalipoproteinemia) being the most common abnormality (39.2% of cases). In these kindreds, 54% had a defined phenotypic familial lipoprotein or apolipoprotein disorder. The following frequencies were observed: Lp(a) excess, 18.6% (includes 12.7% with no other dyslipidemias); hypertriglyceridemia with hypoalphalipoproteinemia, 14.7%; combined hyperlipidemia, 13.7% (11.7% with and 2.0% without hypoalphalipoproteinemia); hyperapobetalipoproteinemia (elevated apo B only), 5%; hypoalphalipoproteinemia, 4%; hypercholesterolemia (elevated LDL only), 3%; hypertriglyceridemia, 1%; decreased apo A-I only, 1%. Overall, 54% of the probands had a familial dyslipidemia; unclassifiable lipid disorders (spouse also affected) were found in 3%. No identifiable familial dyslipidemia was noted in 43% of kindreds of those; nearly half (45%) had a sporadic lipid disorder. Parent-offspring and proband-spouse correlations for these biochemical variables revealed that lipoprotein and apolipoprotein levels are in part genetically determined, with Lp(a) showing the highest degree of parent-offspring correlation. CONCLUSIONS: Our data indicate that more than half of patients with premature CAD have a familial lipoprotein disorder, with Lp(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and combined hyperlipidemia with hypoalphalipoproteinemia being the most common abnormalities.