Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group

BACKGROUND: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population. METHODS: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group. RESULTS: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients. CONCLUSIONS: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.     

Association of risk factor variables and coronary artery disease documented with angiography

Stepwise linear discrimination was used to analyze risk factors in 431 consecutive patients who underwent coronary angiography to determine which variables were most closely associated with coronary artery disease. Twenty-one risk factors were considered: total plasma cholesterol and triglycerides; the cholesterol and triglyceride content of high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low density lipoproteins (VLDL); and the percentage of total cholesterol and triglycerides in each fraction. Age, smoking history, family history, hypertension, diabetes mellitus and relative weight were also considered. Coronary artery disease was assessed using three standard grading scores. There were significant differences in risk factors between males and females. In males, LDL cholesterol and age were selected by multivariate analysis. In females, the ratio of HDL cholesterol to total cholesterol, as well as relative weight, family history, age and smoking were selected. The discriminating value of HDL cholesterol as the percentage of total cholesterol was significantly greater than that of HDL cholesterol itself. Despite highly significant associations between risk factors and the presence of coronary artery disease, the discrimination did not provide sufficient separation of the groups to give results that are useful diagnostically in individual patients.     

Peripheral artery disease and cardiovascular risk factors in the elderly. The Honolulu Heart Program

Peripheral vascular disease as measured by the ankle/brachial blood pressure index (ABI) is associated with increased risk of mortality and morbidity. Few sources of data on the relationship of risk factors to ABI are available for the elderly, especially those > 80 years of age, and minority populations. ABI measurements from the Honolulu Heart Program's fourth reexamination of 3450 ambulatory, elderly Japanese American men indicate that the prevalence of an abnormal ABI, defined as a ratio of < 0.9, was 13.6%, increasing from 8.0% in those 71 to 74 years of age to 27.4% in those 85 to 93 years. Associations that were U or J shaped were present for a number or risk factors (higher rates of abnormality [ABI < 0.9] in those in the lowest and highest risk factor quintiles) in a cross-sectional analysis. Risk factors measured at baseline were also predictive of an abnormal ABI 25 years later, even after adjustment for multiple risk factors. The odds ratio (OR) for an ABI < 0.9 at the 80th percentile of cholesterol compared with that at the 20th percentile was 1.4; the OR for 1-hour postload glucose was 1.3, and for alcohol intake 1.2. The OR associated with hypertension was 1.8 and that for smoking, 2.9 (P < .05 for all ORs). These findings are consistent with ABI being a marker for generalized atherosclerotic disease in old and very old Japanese American men.     

Association between white blood cell count and risk factors of coronary artery disease

BACKGROUND: Epidemiologic studies have shown a correlation between white blood cell (WBC) count and risk of developing myocardial infarction. Aim of this study is to assess the association between WBC and the other risk factors of coronary heart disease in a southern Italian population. METHODS: Baseline data for the 1091 subjects (522 males and 569 females) enrolled in the "Montecorvino Rovella Project" were used to study factors associated with leukocytes. RESULTS: WBC count was significantly higher in smokers (8711.1 +/- 1892 cells/dl) than in ex-smokers (6720 +/- 1608 cells/dl) and in those who never smoked (6674 +/- 1608 cells/dl). By multiple linear regression analysis, WBC count showed a positive association with triglycerides (p < 0.01), cholesterol (p < 0.05) fasting glucose levels (p < 0.01) and diastolic blood pressure (p < 0.05). CONCLUSIONS: In this southern Italian population, elevated WBC count has been associated with other risk factors of coronary artery disease, particularly smoking, and has identified a high risk atherogenic profile. Even if the independency of the role of WBC is still under investigation, WBC count should be taken into account in establishing the coronary risk of apparently healthy people.     

Effects of antihypertensive drugs on coronary artery disease risk: a meta-analysis

1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical significance of these effects and the extent to which they persist during long-term therapy is uncertain. 2. We performed a meta-analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a beta-blocker with beta 2-adrenoceptor intrinsic sympathomimetic activity), enalapril, nifedipine and doxazosin on plasma cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure (BP). 3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations. 4. While there were no differences in antihypertensive efficacy between the drugs, atenolol significantly (P < 0.05) reduced HDL-C and increased total cholesterol, LDL-C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine. 5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 years for celiprolol). 6. The improvement in Framingham equation point scores (systolic BP formula) was significantly (P < 0.05) less for atenolol (-0.54; confidence intervals (CI) -0.29-(-0.78)) than for celiprolol (-1.69; CI -0.68-2.70), doxazosin (-1.67; CI -1.11-(-2.23)), enalapril (-1.43; CI 0.23-(-3.07)) and nifedipine (-1.91; CI -1.22-(-2.59)). Similar results were obtained for the Framingham diastolic BP formula. 7. These results suggest that the adverse effects of atenolol ]on plasma lipids do not improve with prolonged therapy and are theoretically great enough to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect plasma lipids. However it must be emphasized that these are theoretical effects. In order to determine the actual differences between these drugs on CAD end points, studies using these end points are required.     

Lipoprotein(a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease

An interaction between high plasma lipoprotein(a) [Lp(a)], unfavorable plasma lipids, and other risk factors may lead to very high risk for premature CAD. Plasma Lp(a), lipids, and other coronary risk factors were examined in 170 cases with early familial CAD and 165 control subjects to test this hypothesis. In univariate analysis, relative odds for CAD were 2.95 (P < .001) for plasma Lp(a) above 40 mg/dL. Nearly all the risk associated with elevated Lp(a) was found to be restricted to persons with historically elevated plasma total cholesterol (6.72 mmol/L [260 mg/dL] or higher) or with a total/HDL cholesterol ratio > 5.8. Nonlipid risk factors were also found to at least multiply the risk associated with Lp(a). When Lp(a) was over 40 mg/dL and plasma total/HDL cholesterol > 5.8, relative odds for CAD were 25 (P = .0001) in multiple logistic regression. If two or more nonlipid risk factors were also present (including hypertension, diabetes, cigarette smoking, high total homocysteine, or low serum bilirubin), relative odds were 122 (P < 1 x 10(-12)). The ability of nonlipid risk factors to increase risk associated with Lp(a) was dependent on at least a mildly elevated total/HDL cholesterol ratio. In conclusion, high Lp(a) was found to greatly increase risk only if the total/HDL cholesterol ratio was at least mildly elevated, an effect exaggerated by other risk factors. Aggressive lipid lowering in those with elevated Lp(a) therefore appears indicated.     

Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease

Although first suggested at the turn of the 20th century, there is a renewed interest in the infectious theory of atherosclerosis. Studies done in many laboratories around the world over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia, particularly in the early stages of reperfusion. It is also being recognized that the traditional risk factors, such as smoking, dyslipidemia, hypertension and diabetes mellitus, do not explain the presence of coronary atherosclerosis in a large proportion of patients. We believe that in certain genetically susceptible people, infection with very common organisms, such as Chlamydia pneumoniae or cytomegalovirus, may lead to a localized infection and a chronic inflammatory reaction. Persistence of infection may relate to the degree of inflammation and severity of atherosclerosis. Early trials with appropriate antibiotic agents in some patients with a recent history of acute myocardial infarction have led to very salutary results. If patients with an infectious basis of atherosclerosis can be identified, a therapy directed at eradication of the offending organism may be appropriate.     

The risk of coronary artery surgery in women: a matched comparison using preoperative severity of illness scoring

OBJECTIVE: To evaluate the effect of gender on outcomes of coronary artery bypass surgery using a weighted preoperative severity of illness scoring system. DESIGN: Retrospective database review. SETTING: Tertiary care teaching hospital. PARTICIPANTS: The patient population consisted of 2,800 consecutive coronary artery bypass graft (CABG) patients (658 women, 2,142 men), with or without concurrent procedures, operated on between January 1, 1993 and March 31, 1994. MEASUREMENTS AND MAIN RESULTS: Patients were stratified for severity of illness using a 13-element scoring system. The distribution of severity of illness scores and severity of illness-stratified morbidity, hospital mortality, and intensive care unit (ICU) length of stay were compared by chi-square and Fischer's exact test where appropriate. Median duration of intubation and median duration of ICU length of stay were examined by the median test. Female versus male unadjusted mortality (4.9% v 3.0%), total morbidity (15.0% v 9.2%), and average initial ICU length of stay (92.62% v 60.56 hours) were statistically different. Female patients also had significantly more of the following postoperative morbidities: central nervous system complications (focal neurologic deficits, patients > or = 65 years 3.20% v 1.54%; global neurologic deficits, patients > or = 65 years 2.75% v 1.25%), duration of perioperative ventilation that includes the intubation time in the operating room until extubation in the ICU (average = 77.36 hours v 49.20 hours; median = 21.87 v 20.26 hours), and average initial ICU length of stay (average = 92.62 hours v 60.56 hours; median = 42.33 hours v 27.91 hours). However, distribution of severity scores was also different. Women had significantly more preoperative risk factors (p < 0.05): age 65 to 74 years (45.1% v 36.6%), age > or = 75 years (21.3% v 11.9%), chronic obstructive pulmonary disease (10.8% v 6.4%), hematocrit less than 34% (21.9% v 5.5%), diabetes (34.8% v 21.8%), weight less than 65 kg (37.4% v 6.2%), and operative mitral valve insufficiency (9.6% v 6.0%). Stratified by severity, no statistically significant gender differences were found for mortality, morbidity, or ICU length of stay. CONCLUSIONS: Gender does not appear to be an independent risk factor for perioperative morbidity, mortality, or excessive ICU length of stay when patients are stratified by preoperative risk in this severity of illness scoring system.     

A quantitative analysis of the relationship between the Cook-Medley Hostility Scale and traditional coronary artery disease risk factors.

One possible explanation for the association between Cook-Medley Hostility Scale (Ho Scale; W. W. Cook & D. M. Medley, 1954) scores and premature coronary artery disease (CAD) morbidity and mortality is that hostile persons also have elevations on CAD risk factors. Meta-analyses with fixed and random-effects models were used to evaluate the relationship between Ho Scale scores and CAD risk factors in the empirical literature. Ho Scale scores were significantly related to body mass index, waist-to-hip ratio, insulin resistance, lipid ratio, triglycerides, glucose, socioeconomic status (SES), alcohol consumption, and smoking. Although there was also heterogeneity among study outcomes, the results of conservative random effects models provide confidence in the obtained relationships. On the basis of available evidence, researchers might give attention to obesity, insulin resistance, damaging health behaviors, and SES as potential contributing factors in understanding the association between Ho Scale scores and CAD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions

BACKGROUND: Target lesion calcium is a marker for significant coronary artery disease and a determinant of the success of transcatheter therapy. METHODS AND RESULTS: Eleven hundred fifty-five native vessel target lesions in 1117 patients were studied by intravascular ultrasound (IVUS) and coronary angiography. The presence, magnitude, location, and distribution of IVUS calcium were analyzed and compared with the detection and classification (none/mild, moderate, and severe) by angiography. Angiography detected calcium in 440 of 1155 lesions (38%): 306 (26%) moderate calcium and 134 (12%) severe. IVUS detected lesion calcium in 841 of 1155 (73%, P < .0001 versus angiography). The mean arc of lesion calcium measured 115 +/- 110 degrees; the mean length measured 3.5 +/- 3.7 mm. Target lesion calcium was only superficial in 48%, only deep in 28%, and both superficial and deep in 24%. The mean arc of superficial calcium measured 85 +/- 108 degrees; the mean length measured 2.4 +/- 3.4 mm. Three hundred seventy-three of 1155 reference segments (32%) contained calcium (P < .0001 compared with lesion site). The mean arc of reference calcium measured 42 +/- 80 degrees; the mean length measured 1.7 +/- 3.6 mm. Only 44 (4%) had reference calcium in the absence of lesion calcium. Angiographic detection and classification of calcium depended on arcs, lengths, location, and distribution of lesion and reference segment calcium. By discriminant analysis, the classification function for predicting angiographic calcium included the arc of target lesion calcium, the arc of superficial calcium, the length of reference segment calcium, and the location of calcium within the lesion. This model correctly predicted the angiographic detection of calcification in 74.4% of lesions and the angiographic classification (none/moderate/severe) of calcium in 62.8% of lesions. CONCLUSIONS: IVUS detected calcium in > 70% of lesions, significantly more often than standard angiography. Although angiography is moderately sensitive for the detection of extensive lesion calcium (sensitivity, 60% and 85% for three- and four-quadrant calcium, respectively), it is less sensitive for the presence of milder degrees.     

Coronary prone behaviour pattern and risk of coronary heart disease: a case-control study

A pair-matched case-control study was carried out at Govt. Medical College Hospital, Nagpur, to investigate association between coronary prone behaviour pattern (CPBP) and coronary heart disease (CHD). The study included 186 cases of CHD and equal number of controls matched for age, sex and socioeconomic status. CPBP identified to be significantly associated with CHD (OR = 3.23, 95% CI 1.73-6.02). The estimates of attributable risk proportion (ARP) and population attributable risk proportion i(PARP) were calculated to the 69.04 (42.19-83.38) and 16.93 (6.25-31.45) respectively. This study thus identified CPBP as a significant risk factor of CHD in this population.     

Profile of some risk factors for coronary heart disease in a developing country: Nigeria

We examined visual evoked potentials and pattern electroretinograms in a patient with Tolosa-Hunt syndrome associated with optic nerve involvement. The 82-year-old woman developed unilateral painful ophthalmoplegia and visual loss in the right eye. Magnetic resonance imaging showed an abnormal soft-tissue area in the right cavernous sinus and the right orbital apex. Symptoms responded rapidly to treatment with corticosteroid. Visual evoked potentials to flash and pattern stimuli were both remarkably reduced and delayed in the right eye in the acute stage; however they improved to almost normal after steroid therapy. The pattern electroretinogram recorded in the acute stage was normal bilaterally. These results indicate that optic nerve involvement in Tolosa-Hunt syndrome can be mild and reversible.     

Low fat intake and coronary artery disease in a population with higher prevalence of coronary artery disease: the Indian paradox

OBJECTIVE: To determine the association between saturated fat intake and prevalence of coronary artery disease (CAD) and coronary risk factors. DESIGN AND SETTING: Total community cross sectional survey of 20 urban streets out of 196 streets, in the city of Moradabad in north India. SUBJECTS AND METHODS: Adult population between 25 to 64 years inclusive comprised of 1806 subjects (904 men, 902 women) were divided into three groups according to level of saturated fat intake as assessed by 7-day dietary intake records (very low < 7%, low 7 to 10%, high > 10% energy (en) per day). RESULTS: We examined the relationship between CAD risk and levels of % en from fat intake. Low (7 to 10% en/day) and high (> 10% en/day) saturated fat were positively and significantly associated with higher prevalence of CAD. The prevalence of coronary risk factors (hypertension, hypercholesterolemia, obesity and sedentary lifestyle) were significantly higher among subjects with low and high saturated fat intake compared to subjects with very low (< 7%) saturated fat intake. Logistic regression analysis with adjustment for age showed that hypercholesterolemia (OR: men 0.89, women 0.68), hypertension (men 0.92, women 0.56), physical activity (men 0.80, women 0.36), obesity (men 0.82, women 0.88) and smoking (0.70 men) were significant risk factors of CAD. Low and high saturated fat intake were associated with more prestigious occupations, higher and middle income status and better educational levels compared to very low saturated fat intake. CONCLUSIONS: The prevalence of CAD and coronary risk factors was higher in urban Indians with low and high saturated fat intake than those with lower saturated fat intake. These findings suggest that the saturated fat intake should be < 7% en/day for prevention of CAD in Indians.     

Homocysteinaemia after methionine overload as a coronary artery disease risk factor: importance of age and homocysteine levels

BACKGROUND: Homocysteinaemia is now accepted as an independent risk factor for coronary artery disease (CAD). Our goal was to study the influence of age plasma homocysteine level on the CAD risk attributable to homocysteinaemia. METHODS: We studied a group of 98 patients under 55 years of age who had suffered a myocardial infarction 3-12 months before the study. The patients were matched by sex and age with a group of 98 controls without vascular disease. We measured the plasma homocysteine levels 6h after a methionine overload of 0.1 g/kg body weight in patients and controls. Afterwards, the odds ratio for homocysteinaemia was determined by homocysteine level, and that for hyperhomocysteinaemia (homocysteine level > 34 mumol/l) by age group. RESULTS: After methionine loading, the homocysteine odds ratio varied from 0.47 (homocysteine level < 23 mumol/l) to 2.88 (homocysteine level > 34 mumol/l). In patients under the age of 46 the odds ratio for hyperhomocysteinaemia was 18.6. In patients between 46 and 55 years of age the odds ratio for hyperhomocysteinaemia was 1.2. CONCLUSIONS: Low homocysteine levels are protective against CAD, and the higher the homocysteine level the higher the coronary risk appears to be. This clearly means that heterozygosity for cystathionine beta synthase deficiency alone is not enough to explain the vascular risk associated with homocysteinaemia. Hyperhomocysteinemia was shown to be a significant risk factor only in patients under the age of 46 years old.     

Cardiac natriuretic peptides for diagnosis and risk stratification in heart failure: influences of left ventricular dysfunction and coronary artery disease on cardiac hormonal activation

BACKGROUND: Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice. METHODS: We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40). RESULTS: Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group. CONCLUSION: Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.     

Assessing the outcomes of coronary artery bypass graft surgery: how many risk factors are enough? Steering Committee of the Cardiac Care Network of Ontario

OBJECTIVES: We sought to determine whether more comprehensive risk-adjustment models have a significant impact on hospital risk-adjusted mortality rates after coronary artery bypass graft surgery (CABG) in Ontario, Canada. BACKGROUND: The Working Group Panel on the Collaborative CABG Database Project has categorized 44 clinical variables into 7 core, 13 level 1 and 24 level 2 variables, to reflect their relative importance in determining short-term mortality after CABG. METHODS: Using clinical data for all 5,517 patients undergoing isolated CABG in Ontario in 1993, we developed 12 increasingly comprehensive risk-adjustment models using logistic regression analysis of 6 of the Panel's core variables and 6 of the Panel's level 1 variables. We studied how the risk-adjusted mortality rates of the nine cardiac surgery hospitals in Ontario changed as more variables were included in these models. RESULTS: Incorporating six of the core variables in a risk-adjustment model led to a model with an area under the receiver operating characteristic (ROC) curve of 0.77. The ROC curve area slightly improved to 0.79 with the inclusion of six additional level 1 variables (p = 0.063). Hospital risk-adjusted mortality rates and relative rankings stabilized after adjusting for six core variables. Adding an additional six level 1 variables to a risk-adjustment model had minimal impact on overall results. CONCLUSIONS: A small number of core variables appear to be sufficient for fairly comparing risk-adjusted mortality rates after CABG across hospitals in Ontario. For efficient interprovider comparisons, risk-adjustment models for CABG could be simplified so that only essential variables are included in these models.