Coronary Artery Calcification and Family History of Myocardial Infarction in the Dallas Heart Study

ObjectivesThis study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD).BackgroundFH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for.MethodsAmong 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC.ResultsThe mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile.ConclusionsFH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile.     

Validation and Comparison of the Long-Term Prognostic Capability of the SYNTAX Score-II Among 1,528 Consecutive Patients Who Underwent Left Main Percutaneous Coronary Intervention

ObjectivesThis study sought to evaluate the long-term prognostic capacity of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II (SS-II) and compare it with other risk scores among patients undergoing left main percutaneous coronary intervention (LM-PCI).BackgroundRecently, the SS-II was developed in an attempt to individualize and help the decision-making process between PCI and coronary artery bypass graft (CABG) surgery in the management of complex coronary artery disease (CAD). However, there is a paucity of data regarding the utility of SS-II in patients undergoing LM-PCI.MethodsData from 1,528 consecutive patients from a single center undergoing unprotected LM-PCI were prospectively collected. The SS-II and other scores were then derived using patients’ baseline clinical characteristics. Patients were stratified according to tertiles of SS-II for PCI: SS-II ≤21 (n = 508), SS-II >21 and ≤28 (n = 480), and >28 (n = 540). Predictive capability for long-term mortality was compared between angiographic scores and scores combining both angiographic and clinical variables.ResultsAt a mean follow-up of 4.4 years, mortality in the first, second, and third SS-II tertiles was 1.8%, 3.5%, and 9.4%, respectively (p < 0.0001). Multivariate analysis showed SS-II to be a strong independent predictor of mortality (hazard ratio: 1.76, 95% confidence interval: 1.10 to 2.82; p = 0.02) after LM-PCI. When compared with the angiographic SS, scores combining both clinical and angiographic variables, such as the SS-II, were superior in terms of long-term prognostication.ConclusionsResults of this large series of consecutive patients who underwent unprotected LM-PCI suggested that the SS-II has better long-term prognostic power in terms of mortality compared with the original purely angiographic SS.     

Timing of climate variability and grassland productivity

Future climates are forecast to include greater precipitation variability and more frequent heat waves, but the degree to which the timing of climate variability impacts ecosystems is uncertain. In a temperate, humid grassland, we examined the seasonal impacts of climate variability on 27 y of grass productivity. Drought and high-intensity precipitation reduced grass productivity only during a 110-d period, whereas high temperatures reduced productivity only during 25 d in July. The effects of drought and heat waves declined over the season and had no detectable impact on grass productivity in August. If these patterns are general across ecosystems, predictions of ecosystem response to climate change will have to account not only for the magnitude of climate variability but also for its timing.     

Variable selection for discrete survival model with frailty in presence of left truncation and right censoring: Studying association of environmental toxicants on time-to-pregnancy

Understanding the association between mixtures of environmental toxicants and time-to-pregnancy (TTP) is an important scientific question as sufficient evidence has emerged about the impact of individual toxicants on reproductive health and that individuals are exposed to a whole host of toxicants rather than an individual toxicant. Assessing mixtures of chemical effects on TTP poses significant statistical challenges, namely (i) TTP being a discrete survival outcome, typically subject to left truncation and right censoring, (ii) chemical exposures being strongly correlated, (iii) appropriate transformation to account for some lipid-binding chemicals, (iv) non-linear effects of some chemicals, and (v) high percentage of concentration below the limit of detection (LOD) for some chemicals. We propose a discrete frailty modeling framework (named Discnet) that allows selection of correlated covariates while appropriately addressing the methodological issues mentioned above. Discnet is shown to have better and stable false negative and false positive rates compared to alternative methods in various simulation settings. We did a detailed analysis of the pre-conception endocrine disrupting chemicals and TTP from the LIFE study and found that older females, female exposure to cotinine (smoking), DDT conferred a delay in getting pregnant, which was consistent across various approaches to account for LOD as well as non-linear associations.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

Prognostic Value of Initial Left Ventricular Remodeling in Patients With Reperfused STEMI

ObjectivesThis study sought to establish the best definition of left ventricular adverse remodeling (LVAR) to predict outcomes and determine whether its assessment adds prognostic information to that obtained by early cardiac magnetic resonance (CMR).BackgroundLVAR, usually defined as an increase in left ventricular end-diastolic volume (LVEDV) is the main cause of heart failure after an ST-segment elevated myocardial infarction; however, the role of assessment of LVAR in predicting cardiovascular events remains controversial.MethodsPatients with ST-segment elevated myocardial infarction who received percutaneous coronary intervention within 6 h of symptom onset were included (n = 498). CMR was performed during hospitalization (6.2 ± 2.6 days) and after 6 months (6.1 ± 1.8 months). The optimal threshold values of the LVEDV increase and the LV ejection fraction decrease associated with the primary endpoint were ascertained. Primary outcome was a composite of cardiovascular mortality, hospitalization for heart failure, or ventricular arrhythmia.ResultsThe study was completed by 374 patients. Forty-nine patients presented the primary endpoint during follow-up (72.9 ± 42.8 months). Values that maximized the ability to identify patients with and without outcomes were a relative rise in LVEDV of 15% (hazard ratio [HR]: 2.1; p = 0.007) and a relative fall in LV ejection fraction of 3% (HR: 2.5; p = 0.001). However, the predictive model (using C-statistic analysis) failed to demonstrate that direct observation of LVAR at 6 months adds information to data from early CMR in predicting outcomes (C-statistic: 0.723 vs. 0.795).ConclusionsThe definition of LVAR that best predicts adverse cardiovascular events should consider both the increase in LVEDV and the reduction in LV ejection fraction. However, assessment of LVAR does not improve information provided by the early CMR.