Showing papers by "Christopher J. O'Donnell published in 2003"

Mitral Annular Calcification Predicts Cardiovascular Morbidity and Mortality The Framingham Heart Study

Abstract: Background— Mitral annular calcification (MAC) has been associated with stroke in longitudinal, community-based cohorts and cardiovascular disease (CVD) outcomes in many small retrospective studies. Prospective data are limited on the relation of MAC with CVD morbidity and mortality. Methods and Results— We examined the association between MAC assessed by M-mode echocardiography and the incidence of CVD, CVD death, and all-cause death over 16 years of follow-up in the Framingham Heart Study subjects who attended a routine examination between 1979 and 1981. Cox proportional hazards models were used to estimate hazard ratios (HRs) associated with the presence of MAC for each outcome. Of 1197(445 male, 752 female) subjects who had adequate echocardiographic assessment, 14% had MAC. There were 307 incident CVD events and 621 deaths. In multivariable adjusted analyses, MAC was associated with an increased risk of incident CVD (HR, 1.5; 95% CI, 1.1, 2.0), CVD death (HR, 1.6; 95% CI, 1.1, 2.3), and all-cause death (HR, 1.3; 95% CI, 1.04, 1.6). For each 1-mm increase in MAC, the risk of incident CVD, CVD death, and all-cause death increased by ≈10%. Conclusions— The independent association of MAC with incident CVD and CVD death underscores that cardiac calcification is a marker of increased CVD risk.

Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans.

Abstract: The chemokine receptor CX3CR1 is a proinflammatory leukocyte receptor specific for the chemokine fractalkine (FKN or CX3CL1). In two retrospective studies, CX3CR1 has been implicated in the pathogenesis of atherosclerotic cardiovascular disease (CVD) based on statistical association of a common receptor variant named CX3CR1-M280 with lower prevalence of atherosclerosis, coronary endothelial dysfunction, and acute coronary syndromes. However, the general significance of CX3CR1-M280 and its putative mechanism of action have not previously been defined. Here we show that FKN-dependent cell-cell adhesion under conditions of physiologic shear is severely reduced in cells expressing CX3CR1-M280. This was associated with marked reduction in the kinetics of FKN binding as well as reduced FKN-induced chemotaxis of primary leukocytes from donors homozygous for CX3CR1-M280. We also show that CX3CR1-M280 is independently associated with a lower risk of CVD (adjusted odds ratio, 0.60, P = 0.008) in the Offspring Cohort of the Framingham Heart Study, a long-term prospective study of the risks and natural history of this disease. These data provide mechanism-based and consistent epidemiologic evidence that CX3CR1 may be involved in the pathogenesis of CVD in humans, possibly by supporting leukocyte entry into the coronary artery wall. Moreover, they suggest that CX3CR1-M280 is a genetic risk factor for CVD.

Genetic and Environmental Contributions to Atherosclerosis Phenotypes in Men and Women: Heritability of Carotid Intima-Media Thickness in the Framingham Heart Study

Abstract: Background and Purpose— Carotid intima-media thickness (IMT) is a quantitative measure of subclinical atherosclerosis that is predictive of subsequent myocardial infarction and stroke. There is controversy regarding the proportion of variability in IMT explained by genetic factors. Thus, it is uncertain whether carotid IMT is a heritable trait that can be used in genetic studies. Methods— From 1996 to 1998, we measured carotid IMT in 906 men (mean age, 56.7 years) and 980 women (mean age, 57.4 years) from 586 extended families (1630 sib pairs) in the Framingham Offspring cohort. B-mode carotid ultrasonography was used to define mean and maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA). Correlation coefficients were calculated in pairs of siblings. Variance component methods were used to estimate heritability with crude, age- and sex-adjusted, and multivariable-adjusted normalized deviates. Results— Multivariable-adjusted correlation coefficients for mean CCA and ICA IMT wer...

Carotid intima-media thickness is associated with premature parental coronary heart disease: the Framingham Heart Study.

Abstract: Background— A family history of coronary heart disease (CHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. We hypothesized that an important mediator of the familial predisposition to CHD is subclinical atherosclerosis, which is detectable by noninvasive imaging. Methods and Results— We studied 1662 subjects (mean age 57, 51% women) in the Framingham Offspring Study who underwent carotid ultrasonography and had both biological parents in the original (parental) cohort. Parental CHD events were validated prospectively by a physician endpoint committee. The associations of carotid intima-media thickness (IMT) with premature parental CHD (occurring before age 60) and any parental CHD (no age restriction) were examined in age- and multivariable-adjusted analyses. Age-adjusted mean internal carotid IMT was higher in subjects who had at least one parent with premature CHD than in those without a validated parental ...

Metafrontier Functions for the Study of Interregional Productivity Differences

Abstract: The paper uses the concept of metafrontier functions to study regional differences in production technologies. The paper has three components. The first deals with the analytical framework necessary for the definition of metafrontier functions. The second component studies the properties of the metafrontier estimated using nonparametric data envelopment analysis (DEA). The third component focuses on the estimation of metafrontiers within the parametric framework of stochastic frontier analysis (SFA). The empirical application of the models uses cross-country agricultural sector data. The DEA and SFA metafrontiers are presented and discussed.

Evidence for a Gene Influencing Serum Bilirubin on Chromosome 2q Telomere: A Genomewide Scan in the Framingham Study

Abstract: There is an inverse relationship between serum bilirubin concentrations and risk of coronary artery disease. The strength of the association is similar to that of smoking, systolic blood pressure, and HDL cholesterol. We carried out a genomewide scan in a Framingham Heart Study. Our study sample consisted of 330 families with 1,394 sibling pairs, 681 cousin pairs, and 89 avuncular pairs. Using variance-component methods, the heritability was estimated to be 49%±6%, and the genome scan demonstrated significant evidence of linkage of serum bilirubin to chromosome 2q, with a LOD score of 3.8 at location 243 cM. The peak multipoint LOD score is located 1 cM away from the uridine diphosphate glycosyltransferase 1 (UGT1A1) gene. UGT1A1 catalyzes the conjugation of bilirubin with glucuronic acid and thus enhances bilirubin elimination; therefore, it is an important candidate gene for serum bilirubin. Gilbert syndrome, a hyperbilirubinemic syndrome, has a population frequency of 2%–19% and is mainly due to a TA insertion at the promoter region of UGT1A1. Only one other region in the genome produced a multipoint LOD score >1 (LOD = 1.3). Our findings suggest that UGT1A1 may be a major gene controlling serum bilirubin levels in the population.

Metafrontier Functions for the Study of Inter-regional Productivity Differences

Abstract: The paper uses the concept of metafrontier functions to study regional differences in production technologies. The paper has three components. The first deals with the analytical framework necessary for the definition of metafrontier functions. The second component studies the properties of the metafrontier estimated using nonparametric data envelopment analysis (DEA). The third component focuses on the estimation of metafrontiers within the parametric framework of stochastic frontier analysis (SFA). The empirical application of the models uses cross-country agricultural sector data. The DEA and SFA metafrontiers are presented and discussed.

Predictors of long-term mortality after hospitalization for primary unstable angina pectoris and non-ST-elevation myocardial infarction.

Abstract: Data are sparse regarding long-term outcomes after hospitalization for unstable angina pectoris (UAP) and non–ST-elevation myocardial infarction (NSTEMI), as defined by contemporary criteria. We extended follow-up in a preexisting database of unselected patients with primary UAP and NSTEMI admitted by way of the emergency department from 1991 to 1992. Stepwise Cox models were used to identify multivariate predictors of long-term mortality. There were 275 patients (mean age 66 ± 12 years, 33% women) who survived to hospital discharge; 134 patients (49%) died during follow-up (median 9.4 years). Significant multivariate predictors of long-term mortality were: age (hazard ratio [HR] per decade 1.7, 95% confidence interval [CI] 1.4 to 1.9); prior MI (HR 1.7, 95% CI 1.2 to 2.5); diabetes (HR 1.7, 95% CI 1.2 to 2.4); congestive heart failure (HR 2.2, 95% CI 1.5 to 3.4); elevated creatinine (HR 2.5, 95% CI 1.7 to 3.8); elevated leukocyte count (HR 1.7, 95% CI 1.1 to 2.5); systolic blood pressure

Imposing Observation-Varying Equality Constraints Using Generalised Restricted Least Squares

Abstract: Linear equality restrictions derived from economic theory are frequently observation-varying. Except in special cases, Restricted Least Squares (RLS) cannot be used to impose such restrictions without either underconstraining or overconstraining the parameter space. We solve the problem by developing a new estimator that collapses to RLS in cases where the restrictions are observation-invariant. We derive some theoretical properties of our so-called Generalised Restricted Least Squares (GRLS) estimator, and conduct a simulation experiment involving the estimation of a constant returns to scale production function. We find that GRLS significantly outperforms RLS in both small and large samples.

A Bayesian Approach To Imposing Curvature On Distance Functions

Abstract: The estimated parameters of output distance functions frequently violate the monotonicity, quasiconvexity and convexity constraints implied by economic theory, leading to estimated elasticities and shadow prices that are incorrectly signed, and ultimately to perverse conclusions concerning the effects of input and output changes on productivity growth and relative efficiency levels. We show how a Bayesian approach can be used to impose these constraints on the parameters of a translog output distance function. Implementing the approach involves the use of a Gibbs sampler with data augmentation. A Metropolis-Hastings algorithm is also used within the Gibbs to simulate observations from truncated pdfs. Our methods are developed for the case where panel data is available and technical inefficiency effects are assumed to be time-invariant. Two models i?½ a fixed effects model and a random effects model i?½ are developed and applied to panel data on 17 European railways. We observe significant changes in estimated elasticities and shadow price ratios when regularity restrictions are imposed

Testing for Market Power in the Australian Grains and Oilseeds Industries: Further Results

Abstract: Recent empirical studies have found significant evidence of departures from competition in the input side of the bread, breakfast cereal and margarine end-product markets In this study we specify a general duality model of profit maximisation that allows for imperfect competition in the input and output markets of the grains and oilseeds industries The model allows for variable-proportions technologies and can be regarded as a generalisation of several models appearing in the agricultural economics and industrial organisation literatures Aggregate Australian data are used to implement the model for thirteen grains and oilseeds products handled by seven groups of agents The model is estimated in a Bayesian framework Results are reported in terms of (characteristics of) estimated probability distributions for demand and supply elasticities and indexes of market power

Testing for market power in the Australian grains and oilseeds industries: further results

Abstract: Recent empirical studies have found significant evidence of departures from competition in the input side of the bread, breakfast cereal and margarine end-product markets. In this study we specify a general duality model of profit maximisation that allows for imperfect competition in the input and output markets of the grains and oilseeds industries. The model allows for variable-proportions technologies and can be regarded as a generalisation of several models appearing in the agricultural economics and industrial organisation literatures. Aggregate Australian data are used to implement the model for thirteen grains and oilseeds products handled by seven groups of agents. The model is estimated in a Bayesian framework. Results are reported in terms of (characteristics of) estimated probability distributions for demand and supply elasticities and indexes of market power.

Does Excluding Cross-commodity Interactions Matter? Beef and Lamb in Australia

Abstract: Australian broadacre agriculture is typified by strong cross-commodity relationships, where sheep and cattle grazing enterprises compete for pasture and both compete with wheat and other crops for land. Further, some commodities produced by multi-product farms are also used in the production of final products that are substitutes in demand, such as beef and lamb. Economic analyses of the beef market, for example, should also include consideration of the market for the related product, lamb. In this paper the effects of exogenous demand and supply shifters on the wholesale-farm price ratio in two closely related industries, beef and lamb, are examined in a Gardner type of model and the effects of excluding consideration of the cross-commodity interactions is measured. Parameter values were chosen based on previous empirical estimates and the judgement of the authors. Due to uncertainty about many of these parameters, a stochastic approach to sensitivity analysis was adopted where an appropriate probability distribution for each of the unknown parameters was chosen and 5,000 values from each of these distributions were drawn to construct estimated frequency distributions of results. It was found that the value for the general equilibrium elasticity of the beef wholesale to farm price ratio with respect to an exogenous demand shift was slightly larger with lamb cross-commodity effects imposed than without. Therefore the inclusion of cross-commodity relationships increases the responsiveness of the beef/cattle price ratio to the demand shift, but only slightly. The results further suggest that the demand and supply cross-price effects are additive rather than counteracting. Therefore incorrectly excluding the cross-commodity effects may result in large errors.