The spokane heart study: weibull regression and coronary artery disease

Coronary artery calcium is a marker of coronary artery disease and measures the progression of atherosclerosis. It is measured by electron beam computed tomography, and the measured amount of coronary artery calcium is highly skewed to the right and left censored. The distribution of coronary artery calcium appears to be Weibull. We propose a Weibull regression model and we analyze the data using these techniques. Our analysis is based on data from the Spokane Heart Study, which is a cohort of about a thousand subjects that are assessed every two years for coronary artery calcium and risk factors of coronary artery disease. The major focus of the heart study is to determine the natural history of atherosclerosis in its early phase, and we analyze the data as a cross-sectional study with 859 subjects. We would also like to highlight the use of Weibull regression techniques in situations like this, where we have extreme right skewed data. Our main emphasis will be on examining the effect of the traditional risk factors of age, gender, lipid profile (cholesterol and HDL), patient history of lipid abnormality, hypertension, and smoking, and other family history risks on coronary artery calcium. We found that the most important factors influencing the disease were age, sex, and patient history of smoking and lipid abnormality.     

Estimation of the marginal survival time in the presence of dependent competing risks using inverse probability of censoring weighted (IPCW) methods

In medical studies, there is interest in inferring the marginal distribution of a survival time subject to competing risks. The Kyushu Lipid Intervention Study (KLIS) was a clinical study for hypercholesterolemia, where pravastatin treatment was compared with conventional treatment. The primary endpoint was time to events of coronary heart disease (CHD). In this study, however, some subjects died from causes other than CHD or were censored due to loss to follow-up. Because the treatments were targeted to reduce CHD events, the investigators were interested in the effect of the treatment on CHD events in the absence of causes of death or events other than CHD. In this paper, we present a method for estimating treatment group-specific marginal survival curves of time-to-event data in the presence of dependent competing risks. The proposed method is a straightforward extension of the Inverse Probability of Censoring Weighted (IPCW) method to settings with more than one reason for censoring. The results of our analysis showed that the IPCW marginal incidence for CHD was almost the same as the lower bound for which subjects with competing events were assumed to be censored at the end of all follow-up. This result provided reassurance that the results in KLIS were robust to competing risks.     

Stratified proportional subdistribution hazards model with covariate-adjusted censoring weight for case-cohort studies

The case-cohort study design is widely used to reduce cost when collecting expensive covariates in large cohort studies with survival or competing risks outcomes. A case-cohort study dataset consists of two parts: (a) a random sample and (b) all cases or failures from a specific cause of interest. Clinicians often assess covariate effects on competing risks outcomes. The proportional subdistribution hazards model directly evaluates the effect of a covariate on the cumulative incidence function under the non-covariate-dependent censoring assumption for the full cohort study. However, the non-covariate-dependent censoring assumption is often violated in many biomedical studies. In this article, we propose a proportional subdistribution hazards model for case-cohort studies with stratified data with covariate-adjusted censoring weight. We further propose an efficient estimator when extra information from the other causes is available under case-cohort studies. The proposed estimators are shown to be consistent and asymptotically normal. Simulation studies show (a) the proposed estimator is unbiased when the censoring distribution depends on covariates and (b) the proposed efficient estimator gains estimation efficiency when using extra information from the other causes. We analyze a bone marrow transplant dataset and a coronary heart disease dataset using the proposed method.     

A spatial structural equation model with an application to area health needs

Indices of population ‘health need’ are often used to distribute health resources or assess equity in service provision. This article describes a spatial structural equation model incorporating multiple indicators of need and multiple population health risks that affect need (analogous to multiple indicators–multiple causes models). More specifically, the multiple indicator component of the model involves health outcomes such as hospital admissions or mortality, whereas the multiple risk component models the impact on the need for area social and demographic indicators, which proxy population-level risk factors for different diseases. The latent need construct is allowed (under a Bayesian approach) to be spatially correlated, though the prior assumed for need allows a mix of spatially structured and unstructured influences. A case study considers variations in need for coronary heart disease (CHD) care over 625 small areas in London, using recent mortality and hospitalization data (the ‘indicators’) and measures of general ill-health, income and unemployment, which proxy variations in population risk for CHD.     

Confidence interval estimation of the difference between paired AUCs based on combined biomarkers

In many diagnostic studies, multiple diagnostic tests are performed on each subject or multiple disease markers are available. Commonly, the information should be combined to improve the diagnostic accuracy. We consider the problem of comparing the discriminatory abilities between two groups of biomarkers. Specifically, this article focuses on confidence interval estimation of the difference between paired AUCs based on optimally combined markers under the assumption of multivariate normality. Simulation studies demonstrate that the proposed generalized variable approach provides confidence intervals with satisfying coverage probabilities at finite sample sizes. The proposed method can also easily provide P-values for hypothesis testing. Application to analysis of a subset of data from a study on coronary heart disease illustrates the utility of the method in practice.     

Combined survival analysis of cardiac patients by a Cox PH model and a Markov chain

The control and treatment of dyslipidemia is a major public health challenge, particularly for patients with coronary heart diseases. In this paper we propose a framework for survival analysis of patients who had a major cardiac event, focusing on assessment of the effect of changing LDL-cholesterol level and statins consumption on survival. This framework includes a Cox PH model and a Markov chain, and combines their results into reinforced conclusions regarding the factors that affect survival time. We prospectively studied 2,277 cardiac patients, and the results show high congruence between the Markov model and the PH model; both evidence that diabetes, history of stroke, peripheral vascular disease and smoking significantly increase hazard rate and reduce survival time. On the other hand, statin consumption is correlated with a lower hazard rate and longer survival time in both models. The role of such a framework in understanding the therapeutic behavior of patients and implementing effective secondary and primary prevention of heart diseases is discussed here.     

Inference for the Dependent Competing Risks Model with Masked Causes of Failure

The competing risks model is useful in settings in which individuals/units may die/fail for different reasons. The cause specific hazard rates are taken to be piecewise constant functions. A complication arises when some of the failures are masked within a group of possible causes. Traditionally, statistical inference is performed under the assumption that the failure causes act independently on each item. In this paper we propose an EM-based approach which allows for dependent competing risks and produces estimators for the sub-distribution functions. We also discuss identifiability of parameters if none of the masked items have their cause of failure clarified in a second stage analysis (e.g. autopsy). The procedures proposed are illustrated with two datasets.     

Survival models with two phases and length biased sampling

A survival model is presented in which all patients go through a first phase of disease; some then die and the remainder progress to a second phase of disease. The data observed are the path taken and the total sojourn time in the system but not the time, if ever, at which the second phase is entered. The sojourn time in each phase is assumed to be exponentially distributed with possibly different rates for the two phases. Themodel describes serious diseases that progress through one or two phases, and can be extended to multiple phases. The model is extended to account for several length-biased sampling situations. Censoring is considered in all models. Maximum like lihood estimates for the parameters involved exist, are consistent and are a symptotically normal. One of the proposed models is applied to data from the Veterans Administration involving a study of coronary arterial occlusive disease.     

Communicating risk—coronary risk scores

Summary. Cardiovascular disease, particularly heart attack and stroke, is the major cause of death in adults in Europe. The underlying atherosclerosis which causes cardiovascular disease is difficult to treat or reverse, and this has led to intense interest in strategies to prevent its development. The major causes of cardiovascular disease—a high fat diet, tobacco smoking and high blood pressure—are now well known. Control of these risk factors has been shown to reduce the risk of heart attack or stroke. It is now possible with simple information (age, sex, blood pressure level, cholesterol level and information on smoking) to predict the risk of heart attack or stroke fairly accurately. The challenge for the future is to make the information available on risk prediction and on how to reduce risk accessible to lay people, so that they may choose, if they wish, to adopt a life style that will reduce their risk. Such a life style involves healthy food choices, avoidance of overweight, the promotion of leisure exercise and complete avoidance of tobacco. Drug treatments can be extremely effective in controlling both blood pressure and cholesterol levels, but they should be seen as an adjunct to life style measures rather than a primary means of achieving prevention. Practical prevention will only be achieved through dynamic partnerships between the medical profession, Government, voluntary bodies, teaching institutions, insurance companies and paramedical bodies. An outline about how cardiac societies can participate in this process is appended.     

Bayesian hierarchical duration model for repeated events: an application to behavioral observations

This article presents a continuous-time Bayesian model for analyzing durations of behavior displays in social interactions. Duration data of social interactions are often complex because of repeated behaviors (events) at individual or group (e.g. dyad) level, multiple behaviors (multistates), and several choices of exit from a current event (competing risks). A multilevel, multistate model is proposed to adequately characterize the behavioral processes. The model incorporates dyad-specific and transition-specific random effects to account for heterogeneity among dyads and interdependence among competing risks. The proposed method is applied to child–parent observational data derived from the School Transitions Project to assess the relation of emotional expression in child–parent interaction to risk for early and persisting child conduct problems.     

Testing for linearity in generalized linear models using kernel smoothing

A test statistic proposed by Li (1999) for testing the adequacy of heteroscedastic nonlinear regression models using nonparametric kernel smoothers is applied to testing for linearity in generalized linear models. Simulation results for models with centered gamma and inverse Gaussian errors are presented to illustrate the performance of the resulting test compared with log-likelihood ratio tests for specific parametric alternatives. The test is applied to a data set of coronary heart disease status (Hosmer and Lemeshow, (1990).     

Geographic distribution of cardiovascular comorbidities in South Africa: a national cross-sectional analysis

Objectives: We sought to estimate the spatial coexistence of hypertension, coronary heart disease (CHD), stroke and hypercholesterolaemia in South Africa. Design: Cross-sectional. Setting: Sub-Saharan Africa and South Africa. Participants: Data were from 13,827 adults (mean±SD age 39±18 years, 58.4% women) interviewed in the 1998 South African Health and Demographic Survey. Interventions: N/A. Primary and secondary outcome measures: We used multivariate spatial disease models to estimate district-level shared and disease-specific spatial risk components, controlling for known individual risk factors. Results: In univariate analysis, observed prevalence of hypertension and CHD is was high in the south-western parts, and low in the north east. Stroke and high blood cholesterol prevalence appeared to be evenly distributed across the country. In multivariate analysis (adjusting for age, gender, ethnicity, education, urban-dwelling, smoking, alcohol consumption and obesity), hypertension and stroke prevalence were highly concentrated in the south-western parts, whilst CHD and hypercholesterolaemia were highly prevalent in central and top north-eastern corridor, respectively. The shared component, which we took to represent nutrition and other lifestyle factors not accounted for in the model, had a larger effect on cardiovascular disease prevalence in the south-western areas of the country. It appeared to have greater effect on hypertension and CHD. Conclusion: This study suggests a clear geographic distribution of cardiovascular disease in South Africa, driven possibly by shared lifestyle behaviours. These findings might be useful for public health resource allocation in low-income settings.     

Reliability acceptance sampling plans for the Weibull distribution under accelerated Type-I censoring

Type-I censored reliability acceptance sampling plans (RASPs) are developed for the Weibull lifetime distribution with unknown shape and scale parameters such that the producer and consumer risks are satisfied. It is assumed that the life test is conducted at an accelerated condition for which the acceleration factor (AF) is known, and each item is continuously monitored for failure. Sensitivity analyses are also conducted to assess the effect of the uncertainty in the assumed AF on the actual producer and consumer risks, and a method is developed for constructing RASPs that can accommodate the uncertainty in AF.     

Accelerated failure time models for the analysis of competing risks

Competing risks are common in clinical cancer research, as patients are subject to multiple potential failure outcomes, such as death from the cancer itself or from complications arising from the disease. In the analysis of competing risks, several regression methods are available for the evaluation of the relationship between covariates and cause-specific failures, many of which are based on Cox’s proportional hazards model. Although a great deal of research has been conducted on estimating competing risks, less attention has been devoted to linear regression modeling, which is often referred to as the accelerated failure time (AFT) model in survival literature. In this article, we address the use and interpretation of linear regression analysis with regard to the competing risks problem. We introduce two types of AFT modeling framework, where the influence of a covariate can be evaluated in relation to either a cause-specific hazard function, referred to as cause-specific AFT (CS-AFT) modeling in this study, or the cumulative incidence function of a particular failure type, referred to as crude-risk AFT (CR-AFT) modeling. Simulation studies illustrate that, as in hazard-based competing risks analysis, these two models can produce substantially different effects, depending on the relationship between the covariates and both the failure type of principal interest and competing failure types. We apply the AFT methods to data from non-Hodgkin lymphoma patients, where the dataset is characterized by two competing events, disease relapse and death without relapse, and non-proportionality. We demonstrate how the data can be analyzed and interpreted, using linear competing risks regression models.     

Multivariate logistic regression for familial aggregation in age at disease onset

Familial aggregation studies seek to identify diseases that cluster in families. These studies are often carried out as a first step in the search for hereditary factors affecting the risk of disease. It is necessary to account for age at disease onset to avoid potential misclassification of family members who are disease-free at the time of study participation or who die before developing disease. This is especially true for late-onset diseases, such as prostate cancer or Alzheimer's disease. We propose a discrete time model that accounts for the age at disease onset and allows the familial association to vary with age and to be modified by covariates, such as pedigree relationship. The parameters of the model have interpretations as conditional log-odds and log-odds ratios, which can be viewed as discrete time conditional cross hazard ratios. These interpretations are appealing for cancer risk assessment. Properties of this model are explored in simulation studies, and the method is applied to a large family study of cancer conducted by the National Cancer Institute-sponsored Cancer Genetics Network (CGN).     

Design of a time-truncated double sampling plan for a general life distribution

A double sampling plan based on truncated life tests is proposed and designed under a general life distribution. The design parameters such as sample sizes and acceptance numbers for the first and the second samples are determined so as to minimize the average sample number subject to satisfying the consumer's and producer's risks at the respectively specified quality levels. The resultant tables can be used regardless of the underlying distribution as long as the reliability requirements are specified at two risks. In addition, Gamma and Weibull distributions are particularly considered to report the design parameters according to the quality levels in terms of the mean ratios.     

An additive Cox model for coronary heart disease study

Existing models for coronary heart disease study use a set of common risk factors to predict the survival time of the disease, via the standard Cox regression model. For complex relationships between the survival time and risk factors, the linear regression specification in the existing Cox model is not flexible enough to accounts for such relationships. Also, the risk factors are actually risky only when they fall in some risk ranges. For more flexibility in modelling and characterize the risk factors more accurately, we study a semi-parametric additive Cox model, using basis splines and LASSO technique. The proposed model is evaluated by simulation studies and is used for the analysis of a real data in the Strong Heart Study.     

Observational studies,clinical trials,and the women’s health initiative

The complementary roles fulfilled by observational studies and randomized controlled trials in the population science research agenda is illustrated using results from the Women’s Health Initiative (WHI). Comparative and joint analyses of clinical trial and observational study data can enhance observational study design and analysis choices, and can augment randomized trial implications. These concepts are described in the context of findings from the WHI randomized trials of postmenopausal hormone therapy and of a low-fat dietary pattern, especially in relation to coronary heart disease, stroke, and breast cancer. The role of biomarkers of exposure and outcome, including high-dimensional genomic and proteomic biomarkers, in the elucidation of disease associations, will also be discussed in these same contexts.     

A Method for Analyzing Disease-Specific Mortality with Missing Cause of Death Information

In this paper, we examine a method for analyzing competing risks data where the failure type of interest is missing or incomplete, but where there is an intermediate event, and only patients who experience the intermediate event can die of the cause of interest. In some applications, a method called “log-rank subtraction” has been applied to these problems. There has been no systematic study of this methodology, though. We investigate the statistical properties of the method and further propose a modified method by including a weight function in the construction of the test statistic to correct for potential biases. A class of tests is then proposed for comparing the disease-specific mortality in the two groups. The tests are based on comparing the difference of weighted log-rank scores for the failure type of interest. We derive the asymptotic properties for the modified test procedure. Simulation studies indicate that the tests are unbiased and have reasonable power. The results are also illustrated with data from a breast cancer study.     

Accelerating the premiums for annuities,life annuities and life insurance

Abstract

Since it is well-known that it is inevitable to avoid the risks and changes in personal earnings, the types of annuities, life annuities, life insurance and their payment types are important for individuals, customers and financial institutions. In this study the types of annuities, life annuities and life insurance are discussed and some original payment models have been proposed considering both the annuity-due and annuity-immediate situations in increasing and decreasing case of payments. These suggested payment models that have been proposed have brought innovation to the literature in terms of being original.