Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study.

BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults. METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09). CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.

Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort.

BACKGROUND: Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. OBJECTIVE: We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. METHODS: A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. RESULTS: We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze.

Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts.

CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.

Umbilical cord plasma 25-hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study.

BACKGROUND: Recent studies have reported conflicting data on the association between maternal intake of vitamin D during pregnancy and asthma. OBJECTIVE: To assess the influence of prenatal vitamin D status on immune function at birth. METHODS: In an inner-city birth cohort of 568 newborns, 520 of whom had at least one atopic parent, we measured the umbilical cord (UC) plasma concentration of 25-hydroxyvitamin D (25(OH)D) and the cytokine responses of UC blood mononuclear cells (UCMCs) to stimuli including phytohaemagglutinin (PHA), lipopolysaccharide (LPS), and peptidoglycan. In a subset, the UCMC expression of regulatory T cell markers and the suppressive activity of CD4(+) CD25(+) UCMCs were measured. Results The 25th, 50th, and 75th percentiles of UC plasma 25(OH)D level were 15.0, 20.2, and 25.6 ng/mL, respectively. Most cytokine responses of UCMC were not correlated with UC 25(OH)D concentration; however, IFN-γ release after LPS stimulation was weakly positively correlated with UC 25(OH)D concentration (r=0.11, P=0.01). PHA responses were not significantly correlated with 25(OH)D concentration. The UC plasma 25(OH)D concentration was inversely related to the number of CD25(+) (r=-0.20, P=0.06), CD25(Bright) (r=-0.21, P=0.05), and CD25(+) FoxP3 (r=-0.29, P=0.06) cells as a proportion of CD4(+) T cells in UC blood (r=-0.26, P=0.04) but not to the suppressive activity of CD4(+) CD25(+) cells (r=0.17, P=0.22). CONCLUSION AND CLINICAL RELEVANCE: UC 25(OH)D concentration was not correlated with most UCMC cytokine responses to multiple stimuli. There was a suggestion of a weakly positive correlation with IFN-γ release after LPS stimulation. The proportions of CD25(+) , CD25(Bright) , and CD25(+) FoxP3 cells to total CD4(+) T cells were inversely correlated with UC 25(OH)D concentration. Our findings suggest that higher vitamin D levels at birth may be associated with a lower number of T-regulatory cells. Vitamin D status in utero may influence immune regulation in early life.

TSLP polymorphisms are associated with asthma in a sex-specific fashion.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. METHODS: We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). MAIN RESULTS: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. CONCLUSIONS: TSLP variants are associated with asthma in a sex-specific fashion.

Use of the internal mammary artery graft and in-hospital mortality and other adverse outcomes associated with coronary artery bypass surgery.

BACKGROUND: There is clear evidence that patients having coronary artery bypass graft surgeries with an internal mammary artery (IMA) have better long-term survival. Some studies have suggested a short-term protective effect as well but, because older and sicker patients are less likely to receive an IMA graft, there has been concern that the apparent protective effect of the IMA on short-term mortality has been confounded by other risk factors. This study was intended to examine the independent effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors. METHODS AND RESULTS: We studied the use of the left IMA (LIMA) in 21 873 consecutive, isolated, first-time coronary artery bypass graft procedures from 1992 through 1999. A total of 87% of the patients received a LIMA graft. LIMA graft use was associated with a significantly decreased risk of mortality. The crude odds ratio for death (LIMA versus no LIMA) was 0.26 (95% confidence intervals, 0.22, 0.31; P:<0.001). LIMA grafts were protective across all major patient and disease subgroups. The odds ratios by subgroup ranged from 0.13 to 0.48. After adjustment for all major risk factors, the odds ratio for death was 0.40 (95% confidence intervals, 0.33, 0.48; P:<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiring surgery were also less in the LIMA group, although not significantly so. CONCLUSIONS: These data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a strong protective effect on perioperative mortality.

Risks of morbidity and mortality in dialysis patients undergoing coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Although dialysis patients are undergoing CABG with increasing frequency, large studies specifically comparing patient characteristics and procedure-related risks in this population have not been performed. METHODS AND RESULTS: We conducted a regional prospective cohort study of 15,500 consecutive patients undergoing CABG in northern New England from 1992 to 1997. We used multiple logistic regression analysis to examine associations between preoperative dialysis-dependent renal failure and postoperative events and to adjust for potentially confounding variables. The 279 dialysis-dependent renal failure patients (1.8%) were 4.4 times more likely to experience in-hospital mortality than were other CABG patients (12.2% versus 3.0%, respectively; P:<0.001). Dialysis-dependent renal failure patients were older and had more comorbidities and more severe cardiac disease than did other CABG patients. After adjusting for these factors in multivariate analysis, however, dialysis-dependent renal failure patients remained 3.1 times more likely to die after CABG (adjusted odds ratio [OR] 3.1, 95% CI 2.1 to 4.7; P:<0.001). Dialysis-dependent renal failure patients compared with other CABG patients also had a substantially increased risk of postoperative mediastinitis (3.6% versus 1.2%, respectively; adjusted OR 2.4, 95% CI 1.2 to 4.7; P:=0.011) and postoperative stroke (4.3% versus 1.7%, respectively; adjusted OR 2. 1, 95% CI 1.1 to 3.9; P:=0.016), even after controlling for potentially confounding variables. Risks of reexploration for bleeding were similar for patients with and without dialysis-dependent renal failure. CONCLUSIONS: Preoperative dialysis-dependent renal failure is a strong independent risk factor for in-hospital mortality and mediastinitis after CABG.

Identification of variables needed to risk adjust outcomes of coronary interventions: evidence-based guidelines for efficient data collection.

OBJECTIVES: Our objectives were to identify and define a minimum set of variables for interventional cardiology that carried the most statistical weight for predicting adverse outcomes. Though "gaming" cannot be completely avoided, variables were to be as objective as possible and reproducible and had to be predictive of outcome in current databases. BACKGROUND: Outcomes of percutaneous coronary interventions depend on patient risk characteristics and disease severity and acuity. Comparing results of interventions has been difficult because definitions of similar variables differ in databases, and variables are not uniformly tracked. Identifying the best predictor variables and standardizing their definitions are a first step in developing a universal stratification instrument. METHODS: A list of empirically derived variables was first tested in eight cardiac databases (158,273 cases). Three end points (in-hospital death, in-hospital coronary artery bypass graft surgery, Q wave myocardial infarction) were chosen for analysis. Univariate and multivariate regression models were used to quantify the predictive value of the variable in each database. The variables were then defined by consensus by a panel of experts. RESULTS: In all databases patient demographics were similar, but disease severity varied greatly. The most powerful predictors of adverse outcome were measures of hemodynamic instability, disease severity, demographics and comorbid conditions in both univariate and multivariate analyses. CONCLUSIONS: Our analysis identified 29 variables that have the strongest statistical association with adverse outcomes after coronary interventions. These variables were also objectively defined. Incorporation of these variables into every cardiac dataset will provide uniform standards for data collected. Comparisons of outcomes among physicians, institutions and databases will therefore be more meaningful.

Identification of preoperative variables needed for risk adjustment of short-term mortality after coronary artery bypass graft surgery. The Working Group Panel on the Cooperative CABG Database Project.

OBJECTIVES: The purpose of this consensus effort was to define and prioritize the importance of a set of clinical variables useful for monitoring and improving the short-term mortality of patients undergoing coronary artery bypass graft surgery (CABG). BACKGROUND: Despite widespread use of data bases to monitor the outcome of patients undergoing CABG, no consistent set of clinical variables has been defined for risk adjustment of observed outcomes for baseline differences in disease severity among patients. METHODS: Experts with a background in epidemiology, biostatistics and clinical care with an interest in assessing outcomes of CABG derived from previous work with professional societies, government or academic institutions volunteered to participate in this unsponsored consensus process. Two meetings of this ad hoc working group were required to define and prioritize clinical variables into core, level 1 or level 2 groupings to reflect their importance for relating to short-term mortality after CABG. Definitions of these 44 variables were simple and specific to enhance objectivity of the 7 core, 13 level 1 and 24 level 2 variables. Core and level 1 variables were evaluated using data from five existing data bases, and core variables only were examined in an additional two data bases to confirm the consensus opinion of the relative prognostic power of each variable. RESULTS: Multivariable logistic regression models of the seven core variables showed all to be predictive of bypass surgery mortality in some of the seven existing data sets. Variables relating to acuteness, age and previous operation proved to be the most important in all data sets tested. Variables describing coronary anatomy appeared to be least significant. Models including both the 7 core and 13 level 1 variables in five of the seven data sets showed the core variables to reflect 45% to 83% of the predictive information. However, some level 1 variables were stronger than some core variables in some data sets. CONCLUSIONS: A relatively small number of clinical variables provide a large amount of prognostic information in patients undergoing CABG.

Validation of risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty mortality on an independent data set.

OBJECTIVES: We sought to validate recently proposed risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty (PTCA) mortality on an independent data set of high risk patients undergoing PTCA. BACKGROUND: Risk adjustment models for PTCA mortality have recently been reported, but external validation on independent data sets and on high risk patient groups is lacking. METHODS: Between July 1, 1994 and June 1, 1996, 1,476 consecutive procedures were performed on a high risk patient group characterized by a high incidence of cardiogenic shock (3.3%) and acute myocardial infarction (14.3%). Predictors of in-hospital mortality were identified using multivariate logistic regression analysis. Two external models of in-hospital mortality, one developed by the Northern New England Cardiovascular Disease Study Group (model NNE) and the other by the Cleveland Clinic (model CC), were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: In this patient group, an overall in-hospital mortality rate of 3.4% was observed. Multivariate regression analysis identified risk factors for death in the hospital that were similar to the risk factors identified by the two external models. When fitted to the data set, both external models had an area under the ROC curve >0.85, indicating overall excellent model discrimination, and both models were accurate in predicting mortality in different patient subgroups. There was a trend toward a greater ability to predict mortality for model NNE as compared with model CC, but the difference was not significant. CONCLUSIONS: Predictive models for PTCA mortality yield comparable results when applied to patient groups other than the one on which the original model was developed. The accuracy of the two models tested in adjusting for the relatively high mortality rate observed in this patient group supports their application in quality assessment or quality improvement efforts.

Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to assess survival among patients with diabetes and multivessel coronary artery disease (MVD) after percutaneous coronary intervention (PCI) and after coronary artery bypass grafting surgery (CABG). BACKGROUND: The Bypass Angioplasty Revascularization Investigation (BARI) demonstrated that diabetics with MVD survive longer after initial CABG than after initial PCI. Other randomized trials or observational databases have not conclusively reproduced this result. METHODS: A large, regional database was linked to the National Death Index to assess five-year mortality. Of 7,159 consecutive patients with diabetes who underwent coronary revascularization in northern New England during 1992 to 1996, 2,766 (38.6%) were similar to those randomized in the BARI trial. Percutaneous coronary intervention was the initial revascularization strategy in 736 patients and CABG in 2,030. Cox proportional hazards regression was used to calculate risk-adjusted hazard ratios (HR) and 95% confidence intervals (CI 95%). RESULTS: Patients who underwent PCI were younger, had higher ejection fractions and less extensive coronary disease. After adjusting for differences in baseline clinical characteristics, patients with diabetes treated with PCI had significantly greater mortality relative to those undergoing CABG (HR = 1.49; CI 95%: 1.02 to 2.17; p = 0.037). Mortality risk tended to increase more among 1,251 patients with 3VD (HR = 2.02; CI 95%: 1.04 to 3.91; p = 0.038) than among 1,515 patients with 2VD (HR = 1.33; CI 95%: 0.84 to 2.1; p = 0.21). CONCLUSIONS: In this analysis of a large regional contemporary database of patients with diabetes selected to be similar to those enrolled in the BARI trial, five-year mortality was significantly increased after initial PCI. This supports the BARI conclusion on initial revascularization of patients with diabetes and MVD.

Survival analysis and risk factors for mortality in transplantation and staged surgery for hypoplastic left heart syndrome.

OBJECTIVES: We compared survival in treatment strategies and determined risk factors for one-year mortality for hypoplastic left heart syndrome (HLHS) using intention-to-treat analysis. BACKGROUND: Staged revision of the native heart and transplantation as treatments for HLHS have been compared in treatment-received analyses, which can bias results. METHODS: Data on 231 infants with HLHS, born between 1989 and 1994 and intended for surgery, were collected from four pediatric cardiac surgical centers. Status at last contact for survival analysis and mortality at one year for risk factor analysis were the outcome measures. RESULTS: Survival curves showed improved survival for patients intended for transplantation over patients intended for staged surgery. One-year survival was 61% for transplantation and 42% for staged surgery (p < 0.01); five-year survival was 55% and 38%, respectively (p < 0.01). Survival curves adjusted for preoperative differences were also significantly different (p < 0.001). Waiting-list mortality accounted for 63% of first-year deaths in the transplantation group. Mortality with stage 1 surgery accounted for 86% of that strategy's first-year mortality. Birth weight <3 kg (odds ratio [OR] 2.4), highest creatinine > or =2 mg/dL (OR 4.7), restrictive atrial septal defect (OR 2.7) and, in staged surgery, atresia of one (OR 4.2) or both (OR 11.0) left-sided valves produced a higher risk for one-year mortality. CONCLUSIONS: Transplantation produced significantly higher survival at all ages up to seven years. Patients with atresia of one or both valves do poorly in staged surgery and have significantly higher survival with transplantation. This information may be useful in directing patients to the better strategy for them.

A comparison of treatment strategies for hypoplastic left heart syndrome using decision analysis.

OBJECTIVES: We sought to identify the optimal treatment strategy for hypoplastic left heart syndrome (HLHS). BACKGROUND: Surgical treatment of HLHS involves either transplantation (Tx) or staged palliation of the native heart. Identifying the best treatment for HLHS requires integrating individual patient risk factors and center-specific data. METHODS: Decision analysis is a modeling technique used to compare six strategies: staged surgery; Tx; stage 1 surgery as an interim to Tx; and listing for transplant for one, two, or three months before performing staged surgery if a donor is unavailable. Probabilities were derived from current literature and a dataset of 231 patients with HLHS born between 1989 and 1994. The goal was to maximize first-year survival. RESULTS: If a donor is available within one month, Tx is the optimal choice, given baseline probabilities; if no donor is found by the end of one month, stage 1 surgery should be performed. When survival and organ donation probabilities were varied, staged surgery was the optimal choice for centers with organ donation rates < 10% in three months and with stage 1 mortality <20%. Waiting one month on the transplant list optimized survival when the three-month organ donation rate was > or =30%. Performing stage 1 surgery before listing, or performing stage 1 surgery after an unsuccessful two- or three-month wait for transplant, were almost never optimal choices. CONCLUSIONS: The best strategy for centers that treat patients with HLHS should be guided by local organ availability, stage 1 surgical mortality and patient risk factors.

Changing outcomes in percutaneous coronary interventions: a study of 34,752 procedures in northern New England, 1990 to 1997. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to evaluate the changing outcomes of percutaneous coronary interventions (PCIs) in recent years. BACKGROUND: The field of interventional cardiology has seen considerable growth in recent years, both in the number of patients undergoing procedures and in the development of new technology. In view of recent changes, we evaluated the experience of a large, regional registry of PCIs and outcomes over time. METHODS: Data were collected from 1990 to 1997 on 34,752 consecutive PCIs performed at all hospitals in Maine (two), New Hampshire (two) and Vermont (one) supporting these procedures, and one hospital in Massachusetts. Univariate and multivariate regression analyses were used to control for case mix. Clinical success was defined as at least one lesion dilated to <50% residual stenosis and no adverse outcomes. In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction and mortality. RESULTS: Over time, the population undergoing PCIs tended to be older with increasing comorbidity. After adjustment for case mix, clinical success continued to improve from a low of 88.2% in earlier years to a peak of 91.9% in recent years (p trend <0.001). The rate of emergency CABG after PCI fell in recent years from a peak of 2.3% to 1.3% (p trend <0.001). Mortality rates decreased slightly from 1.2% to 1.1% (p trend 0.007). CONCLUSIONS: There has been a significant improvement in clinical outcomes for patients undergoing PCIs in northern New England, including a significant decline in the need for emergency CABG.

Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994-1996. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: Using recent data, we sought to identify risk factors associated with in-hospital mortality among patients undergoing percutaneous coronary interventions. BACKGROUND: The ability to accurately predict the risk of an adverse outcome is important in clinical decision making and for risk adjustment when assessing quality of care. Most clinical prediction rules for percutaneous coronary intervention (PCI) were developed using data collected before the broader use of new interventional devices. METHODS: Data were collected on 15,331 consecutive hospital admissions by six clinical centers. Logistic regression analysis was used to predict the risk of in-hospital mortality. RESULTS: Variables associated with an increased risk of in-hospital mortality included older age, congestive heart failure, peripheral or cerebrovascular disease, increased creatinine levels, lowered ejection fraction, treatment of cardiogenic shock, treatment of an acute myocardial infarction, urgent priority, emergent priority, preprocedure insertion of an intraaortic balloon pump and PCI of a type C lesion. The receiver operating characteristic area for the predicted probability of death was 0.88, indicating a good ability to discriminate. The rule was well calibrated, predicting accurately at all levels of risk. Bootstrapping demonstrated that the estimate was stable and performed well among different patient subsets. CONCLUSIONS: In the current era of interventional cardiology, accurate calculation of the risk of in-hospital mortality after a percutaneous coronary intervention is feasible and may be useful for patient counseling and for quality improvement purposes.

Operator volume and outcomes in 12,998 percutaneous coronary interventions. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to determine whether there is a relation between operator volume and outcomes for percutaneous coronary interventions (PCIs). BACKGROUND: A 1993 American College of Cardiology/American Heart Association task force stated that cardiologists should perform > or = 75 procedures/year to maintain competency in PCIs; however, there were limited data available to support this statement. METHODS: Data were collected from 1990 through 1993 on 12,988 PCIs (12,118 consecutive hospital admissions) performed by 31 cardiologists at two hospitals in New Hampshire and two in Maine and one hospital in Massachusetts supporting these procedures. Operators were categorized into terciles based on annualized volume of procedures. Univariate and multivariate regression analyses were used to control for case-mix. Successful outcomes included angiographic success (all lesions attempted dilated to < 50% residual stenosis) and clinical success (at least one lesion dilated to < 50% residual stenosis and no adverse outcomes). In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction (MI) and death. RESULTS: After adjustment for case-mix, higher angiographic (low, middle and high terciles: 84.7%, 86.1% and 90.3%, p-trend 0.006) and clinical success rates (85.8%, 88.0% and 90.7%, p-trend 0.025), with fewer referrals to CABG (4.54%, 3.75% and 2.49%, p-trend <0.001), were seen as operator volume increased. There was a trend toward higher MI rates for high volume operators (2.00%, 1.98% and 2.57%, p-trend 0.06); all terciles had similar in-hospital mortality rates (1.09%, 0.96% and 1.05%, p-trend 0.8). CONCLUSIONS: There is a significant relation between operator volume and outcomes in PCIs. Efforts should be directed toward understanding why high volume operators are more successful and encounter fewer adverse outcomes.

Occupation and risk of nonfatal myocardial infarction.

BACKGROUND: While some analytic studies have suggested that individuals in occupations representing higher compared with lower socioeconomic status have a decreased risk of coronary heart disease, it is unclear whether occupation itself has an etiologic role in the development of coronary heart disease or whether differences in as yet uncontrolled coronary risk factors may account for these differences in risk. METHODS: White-collar vs blue-collar occupation and risk of coronary heart disease was evaluated among 230 male patients hospitalized for a first myocardial infarction and 222 control subjects of the same age, sex, and neighborhood of residence. Information on coronary risk factors was obtained from home interviews, and blood specimens were drawn to test lipid and lipoprotein levels. Usual occupation was dichotomized into white-collar and blue-collar occupation according to the Edwards' classification. RESULTS: The relative risk of myocardial infarction of white-collar compared with blue-collar workers was 0.74 (95% confidence interval, 0.46 to 1.19) after controlling for age, cigarette smoking, family history of premature myocardial infarction, history of treatment for high blood pressure, body mass index, history of diabetes, alcohol consumption, type A personality, leisure-time physical activity, total calories, and percentage of calories consumed as saturated fat. However, there was no residual association after control for high-density lipoprotein cholesterol yielding a relative risk of 0.98 (95% confidence interval, 0.59 to 1.63). CONCLUSIONS: These results suggest that white-collar occupation per se does not appear to protect from coronary heart disease. Any apparent protective effect on myocardial infarction that has been previously observed in white-collar compared with blue-collar workers may be attributable to differences in high-density lipoprotein cholesterol levels.

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

Calcium and phosphorus supplementation of iron-fortified infant formula: no effect on iron status of healthy full-term infants.

One objective of this clinical trial was to determine whether calcium and phosphorus supplementation of infant formula affects the iron status of healthy full-term infants. One hundred three infants were randomly assigned to receive iron-fortified, cow milk-based infant formula (465 mg Ca and 317 mg P/L) or the same formula with added calcium glycerophosphate (1800 mg Ca and 1390 mg P/L) for 9 mo. Reported calcium intake for supplemented infants was about four times that of control infants, ranging from a mean of 1741 mg/d at baseline to 1563 mg/d at 9 mo. There was no difference by treatment group in mean or median change from baseline of serum ferritin, total-iron-binding capacity, erythrocyte protoporphyrin, or hematocrit at 4 and 9 mo after enrollment. Incidence of iron deficiency was similar for both groups and no infant developed iron deficiency anemia during the trial. This study indicates that the well-documented inhibitory effect of calcium and phosphorus on iron absorption is not clinically important in infants fed iron-fortified infant formula.

Randomized trial of calcium glycerophosphate-supplemented infant formula to prevent lead absorption.

BACKGROUND: Although additional dietary calcium is recommended frequently to reduce the risk of lead poisoning, its role in preventing lead absorption has not been evaluated clinically. OBJECTIVE: The objective was to determine the safety and to estimate the size of the effect of calcium- and phosphorus-supplemented infant formula in preventing lead absorption. DESIGN: One hundred three infants aged 3.5-6 mo were randomly assigned to receive iron-fortified infant formula (465 mg Ca and 317 mg P/L) or the same formula with added calcium glycerophosphate (1800 mg Ca and 1390 mg P/L) for 9 mo. RESULTS: There was no significant difference between groups in the mean ratio of urinary calcium to creatinine, serum calcium and phosphorus, or change in iron status (serum ferritin, total iron binding capacity). At month 4, the median (+/-SD) increase from baseline in blood lead concentration for the supplemented group was 57% of the increase for the control group (0.04 +/- 0.09 compared with 0.07 +/- 0.10 micromol/L; P = 0.039). This effect was attenuated during the latter half of the trial, with an overall median increase in blood lead concentration from baseline to month 9 of 0.12 +/- 0.13 micromol/L for the control group and 0.10 +/- 0.18 micromol/L for the supplemented group (P = 0.284). CONCLUSIONS: Supplementation did not have a measurable effect on urinary calcium excretion, calcium homeostasis, or iron status. The significant effect on blood lead concentrations during the first 4 mo was in the direction expected; however, because this was not sustained throughout the 9-mo period we cannot conclude that the calcium glycerophosphate supplement prevented lead absorption in this population.