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.

A model for cardiopulmonary bypass redesign.

INTRODUCTION: A portion of patients undergoing cardiac surgery may develop focal and/or subtle brain injuries secondary to cardiac surgery. There is evidence that, in some cases, these injuries may be related to cardiopulmonary bypass (CPB). Embolism and hypoperfusion are the dominant mechanisms for focal neurologic injuries among coronary artery bypass graft (CABG) surgery patients. Recent studies suggest that these mechanisms may also produce the more prevalent subtle neurological deficits. The aim of our current work is to obtain a thorough understanding of the processes of care associated with the production of embolic activity, cerebral hypoperfusion, and hemodynamic aberrations that often occur during CPB. METHODS: We developed a system for simultaneous recording of physiologic parameters, embolic activity in the CPB circuit and in the cerebral arteries, and near infrared regional cerebral oxyhemoglobin saturation (NIRS) during cardiac surgery. All data were synchronized with a video recording of the surgical procedure. Periods of embolic activity and NIRS were subsequently related to surgical and CPB processes of care through a systematic review of the patient's surgical case video. RESULTS: To date, we have enrolled 47 patients undergoing coronary and/or valvular procedures. We have observed wide variation across patients in detected cerebral embolic counts, NIRS and physiologic parameters. We have identified increased embolic counts in the CPB circuit related to specific processes and events such as the method of venous drainage, the entrainment of air in the venous line, the injection of medications into the CPB circuit and blood sampling from the CPB circuit. A portion of detected changes in NIRS were related to periods of hypotension and positioning of the heart during the construction of distal coronary artery grafts on the posterior coronary artery vessels. SUMMARY: Use of this model provides the surgical team with detailed information regarding the contribution of CPB to the creation of precursors of neurological injury. This system provides meaningful data to guide the surgical team in the redesign of the CPB system and associated techniques.

Morbidities in patients with hypoplastic left heart syndrome.

We sought to document morbidities and growth for patients with hypoplastic left heart syndrome (HLHS) to inform the initial surgical decision and understand healthcare needs. Data were obtained on 137 patients with HLHS, born between 1989 and 1994, who survived staged surgery ( n = 62) or transplantation ( n = 75) and had follow-up information available from four pediatric cardiac surgical centers. In patients with HLHS older than 1 year of age at follow-up, 93% experienced at least one major postsurgical morbidity. Morbidities depended on the surgery received. Hypertension, renal compromise, and abnormal infections were more common in transplanted patients than staged surgery patients. Staged surgery patients used more anticongestive medications and experienced more morbidities requiring interventional catheterization than did transplanted patients. Rejection was common for transplanted patients. On average these children spent 23 days per year in the hospital. Patients with HLHS were small for their age; 43% of staged surgery patients weighed below the third percentile at last information, compared to 19% of transplanted patients ( p = 0.003). The median height percentile was the 10th in both groups. Normal activity level was reported in more transplanted patients (90%) than staged surgery patients (49%; p < 0.001). Trade-offs between mortality and morbidity outcomes can help inform the initial surgical decision.

In-hospital outcomes of off-pump versus on-pump coronary artery bypass procedures: a multicenter experience.

BACKGROUND: Concern about the possible adverse effects of the cardiopulmonary bypass (CPB) pump and advances in retractors and operative techniques to access all coronary segments have resulted in increased interest in off-pump coronary artery bypass (OPCAB) procedures. Four of the Northern New England Cardiovascular Disease Study Group centers initiated OPCAB programs in 1998. We compared the preoperative risk profiles and in-hospital outcomes of patients done off-pump with those done by conventional coronary artery bypass (CCAB) with CPB. METHODS: Between 1998 and 2000, 1,741 OPCAB and 6,126 CCAB procedures were performed at these four medical centers. Minimally invasive direct coronary artery bypass grafting procedures were excluded. Data were available for patient and disease risk factors, extent of coronary disease and adverse in-hospital outcomes. RESULTS: The OPCAB and CCAB groups were somewhat different in their preoperative patient and disease characteristics. The OPCAB patients were more likely to be female and to have peripheral vascular disease. The CCAB patients were more likely to have an ejection fraction less than 0.40 and be urgent or emergent at operation. However, overall predicted risk of in-hospital mortality, based on preoperative factors, was similar in the OPCAB and CCAB groups; the mean predicted risk was 2.6% (p = 0.567). Crude rates of mortality (2.54% OPCAB versus 2.57%, CCAB), intraoperative or postoperative stroke (1.33% versus 1.82%), mediastinitis (1.10% versus 1.37%), and return to the operating room for bleeding (3.46% versus 2.93%) did not differ significantly. The OPCAB patients did have a statistically significant reduction in the need for intraoperative or postoperative intraaortic balloon pump support (2.31% versus 3.41%; p = 0.023) and in the incidence of postoperative atrial fibrillation (21.21% versus 26.31%; p < 0.001). Adjustment for preoperative risk factors and extent of coronary disease did not substantially change the crude results. Median postoperative length of stay was significantly shorter (5 days versus 6 days, p < 0.001) for OPCAB patients than for CCAB patients. CONCLUSIONS: This multicenter study showed that patients having OPCAB are not exposed to a greater risk of short-term adverse outcomes. These data also provided evidence that patients having OPCAB have significantly lower need for intraoperative or postoperative intraaortic balloon pump, lower rates of postoperative atrial fibrillation, and a shorter length of stay.

Heritability of longitudinal change in lung function. The Framingham study.

There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV(1), FVC, and FEV(1)/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV(1), FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene-environment interactions.

Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study.

The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.

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.

Effects of physical interventions on house dust mite allergen levels in carpet, bed, and upholstery dust in low-income, urban homes.

House dust mite allergen exposure is a postulated risk factor for allergic sensitization, asthma development, and asthma morbidity; however, practical and effective methods to mitigate these allergens from low-income, urban home environments remain elusive. The purpose of this study was to assess the feasibility and effectiveness of physical interventions to mitigate house dust mite allergens in this setting. Homes with high levels of house dust mite allergen (Der f 1 + Der p 1 > or = 10 microg/g dust by enzyme-linked immunosorbent assay) in the bed, bedroom carpet, and/or upholstered furniture were enrolled in the study. Carpets and upholstered furniture were subjected to a single treatment of either dry steam cleaning plus vacuuming (carpet only) or intensive vacuuming alone. Bed interventions consisted of complete encasement of the mattress, box spring, and pillows plus either weekly professional or in-home laundering of nonencased bedding. Dust samples were collected at baseline and again at 3 days (carpet and upholstery only) and 2, 4, and 8 weeks posttreatment. We compared pretreatment mean allergen concentrations and loads to posttreatment values and performed between-group analyses after adjusting for differences in the pretreatment means. Both dry steam cleaning plus vacuuming and vacuuming alone resulted in a significant reduction in carpet house dust mite allergen concentration and load (p < 0.05). Levels approached pretreatment values by 4 weeks posttreatment in the intensive vacuuming group, whereas steam cleaning plus vacuuming effected a decrease that persisted for up to 8 weeks. Significant decreases in bed house dust mite allergen concentration and load were obtained in response to encasement and either professional or in-home laundering (p < 0.001). Between-group analysis revealed significantly less postintervention house dust mite allergen load in professionally laundered compared to home-laundered beds (p < 0.05). Intensive vacuuming and dry steam cleaning both caused a significant reduction in allergen concentration and load in upholstered furniture samples (p < 0.005). Based on these data, we conclude that physical interventions offer practical, effective means of reducing house dust mite allergen levels in low-income, urban home environments.

Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.

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.

Improved in-hospital mortality in women undergoing coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Few studies have examined the changes in in-hospital mortality for women over time. We describe the changing case mix and mortality for women undergoing coronary artery bypass grafting (CABG) from 1987 to 1997 in northern New England. METHODS: Data were collected on 8,029 women and 21,139 men undergoing isolated CABG. The study consisted of three time periods (1987 to 1989, 1990 to 1992, and 1993 to 1997) to account for regional efforts to improve quality of care that occurred during 1990 to 1992. RESULTS: Compared with 1987 to 1989, women undergoing CABG in 1993 to 1997 were older, had poorer ventricular function, and more often required urgent or emergency operations. The crude and adjusted mortality rates for both women and men decreased significantly over time. The absolute magnitude of the change in adjusted rates was greater for women (3.1%) than for men (1.5%). Although women represented only 28% of the study population, the decrease in their mortality accounted for 44% of the total decrease in adjusted mortality during the study period. CONCLUSIONS: Over the last decade there has been a marked decrease in CABG mortality for women, despite a worsening case mix.

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.

Aortic valve replacement: current clinical practice and opportunities for quality improvement.

This is a review of the current clinical practice and opportunities for quality improvement in aortic valve replacement surgery. The topics include trends and regional variation in procedure rates, and changes in the use of aortic valve replacement among the elderly. Recent developments guiding the choice of prosthetic valves and trends in in-hospital mortality rates for aortic valve surgery are summarized. Lastly, a discussion of topics relevant to clinical practice improvement including the implementation of clinical practice guidelines, the need for consensus on risk adjustment, better understanding of volume-outcome effects, and the opportunities for comprehensive assessment of aortic valve surgery.

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.

Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.

Predicting the risk of death from heart failure after coronary artery bypass graft surgery.

UNLABELLED: Heart failure is the most common cause of death among coronary artery bypass graft (CABG) patients. In addition, most variation in observed mortality rates for CABG surgery is explained by fatal heart failure. The purpose of this study was to develop a clinical risk assessment tool so that clinicians can rapidly and easily assess the risk of fatal heart failure while caring for individual patients. Using prospective data for 8,641 CABG patients, we used logistic regression analysis to predict the risk of fatal heart failure. In multivariate analysis, female sex, prior CABG surgery, ejection fraction <40%, urgent or emergency surgery, advanced age (70-79 yr and >80 yr), peripheral vascular disease, diabetes, dialysis-dependent renal failure and three-vessel coronary disease were significant predictors of fatal postoperative heart failure. A clinical risk assessment tool was developed from this logistic regression model, which had good discriminating characteristics (receiver operating characteristic clinical source = 0.75, 95% confidence interval: 0.71, 0.78). IMPLICATIONS: In contrast to previous cardiac surgical scoring systems that predicted total mortality, we developed a clinical risk assessment tool that evaluates risk of fatal heart failure. This distinction is relevant for quality improvement initiatives, because most of the variation in CABG mortality rates is explained by postoperative heart failure.