Maximum Likelihood Estimation for Semiparametric Regression Models with Interval-Censored Multi-State Data

Interval-censored multi-state data arise in many studies of chronic diseases, where the health status of a subject can be characterized by a finite number of disease states and the transition between any two states is only known to occur over a broad time interval. We formulate the effects of potentially time-dependent covariates on multi-state processes through semiparametric proportional intensity models with random effects. We adopt nonparametric maximum likelihood estimation (NPMLE) under general interval censoring and develop a stable expectation-maximization (EM) algorithm. We show that the resulting parameter estimators are consistent and that the finite-dimensional components are asymptotically normal with a covariance matrix that attains the semiparametric efficiency bound and can be consistently estimated through profile likelihood. In addition, we demonstrate through extensive simulation studies that the proposed numerical and inferential procedures perform well in realistic settings. Finally, we provide an application to a major epidemiologic cohort study.Comment: 49 page

Associations Between the Serum Metabolome and All-Cause Mortality Among African Americans in the Atherosclerosis Risk in Communities (ARIC) Study

Early and accurate identification of people at high risk of premature death may assist in the targeting of preventive therapies in order to improve overall health. To identify novel biomarkers for all-cause mortality, we performed untargeted metabolomics in the Atherosclerosis Risk in Communities (ARIC) Study. We included 1,887 eligible ARIC African Americans, and 671 deaths occurred during a median follow-up period of 22.5 years (1987–2011). Chromatography and mass spectroscopy identified and quantitated 204 serum metabolites, and Cox proportional hazards models were used to analyze the longitudinal associations with all-cause and cardiovascular mortality. Nine metabolites, including cotinine, mannose, glycocholate, pregnendiol disulfate, α-hydroxyisovalerate, N-acetylalanine, andro-steroid monosulfate 2, uridine, and γ-glutamyl-leucine, showed independent associations with all-cause mortality, with an average risk change of 18% per standard-deviation increase in metabolite level (P < 1.23 × 10−4). A metabolite risk score, created on the basis of the weighted levels of the identified metabolites, improved the predictive ability of all-cause mortality over traditional risk factors (bias-corrected Harrell's C statistic 0.752 vs. 0.730). Mannose and glycocholate were associated with cardiovascular mortality (P < 1.23 × 10−4), but predictive ability was not improved beyond the traditional risk factors. This metabolomic analysis revealed potential novel biomarkers for all-cause mortality beyond the traditional risk factors

Association of Educational Attainment With Lifetime Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities Study

Estimates of lifetime risk may help raise awareness of the extent to which educational inequalities are associated with risk of cardiovascular disease (CVD). To estimate lifetime risks of CVD according to categories of educational attainment. Participants were followed from 1987 through December 31, 2013. All CVD events (coronary heart disease, heart failure, and stroke) were confirmed by physician review and International Classification of Diseases codes. A total of 13 948 whites and African Americans who were 45 to 64 years old and free of CVD at baseline were included from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota). The data analysis was performed from June 7 to August 31, 2016. Educational attainment. We used a life table approach to estimate lifetime risks of CVD from age 45 through 85 years according to educational attainment. We adjusted for competing risks of death from underlying causes other than CVD. The sample of 13 948 participants was 56% female and 27% African American. During 269 210 person-years of follow-up, we documented 4512 CVD events and 2401 non-CVD deaths. Educational attainment displayed an inverse dose-response relation with cumulative risk of CVD, which became evident in middle age, with the most striking gap between those not completing vs completing high school. In men, lifetime risks of CVD were 59.0% (95% CI, 54.0%-64.1%) for grade school, 52.5% (95% CI, 47.7%-56.8%) for high school education without graduation, 50.9% (95% CI, 47.3%-53.9%) for high school graduation, 47.2% (95% CI, 41.5%-52.5%) for vocational school, 46.4% (95% CI, 42.8%-49.6%) for college with or without graduation, and 42.2% (95% CI, 36.6%-47.0%) for graduate/professional school; in women, 50.8% (95% CI, 45.7%-55.8%), 49.3% (95% CI, 45.1%-53.1%), 36.3% (95% CI, 33.4%-39.1%), 32.2% (95% CI, 26.0%-37.3%), 32.8% (95% CI, 29.1%-35.9%), and 28.0% (95% CI, 21.9%-33.3%), respectively. Educational attainment was inversely associated with CVD even within categories of family income, income change, occupation, or parental educational level. More than 1 in 2 individuals with less than high school education had a lifetime CVD event. Educational attainment was inversely associated with the lifetime risk of CVD, regardless of other important socioeconomic characteristics. Our findings emphasize the need for further efforts to reduce CVD inequalities related to educational disparities

Recent Findings in the Genetics of Blood Pressure and Hypertension Traits

We provide an overview of ongoing discovery efforts in the genetics of blood pressure (BP) and hypertension (HTN) traits. Two large genome-wide association meta-analyses of individuals of European descent were recently published, revealing ~13 new loci for BP traits. Only two of these loci harbor genes in a pathway known to affect BP (CYP17A1 and NPPA/NPPB). Functional variants in these loci are still unknown. Few genome-wide association studies (GWAS) of complex diseases have been published from non-European populations. The study of populations with different evolutionary history and linkage disequilibrium (LD) structure, such as individuals of African ancestry, may provide an opportunity to further narrow these regions to identify the causal gene(s). Several collaborative efforts toward discovery of low-frequency variants and copy number variation for BP traits are currently underway. As evidence for new loci for complex diseases accumulates the assessment of the epidemiologic architecture of these variants in populations assumes higher priority. The impact of public health–relevant contexts such as diet, physical activity, psychosocial factors, and aging has not been examined for most common variants associated with BP

Dietary intake and peripheral arterial disease incidence in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Peripheral arterial disease (PAD) is a costly source of morbidity and mortality among older persons in the United States. Dietary intake plays a role in the development of atherosclerotic cardiovascular disease; however, few studies have examined the relation of food intake or dietary patterns with PAD

Do all components of the metabolic syndrome cluster together in U.S. Hispanics/Latinos? Results from the Hispanic Community Health study/Study of Latinos

Metabolic syndrome (MetS), the clustering of several risk factors for cardiovascular disease, is highly prevalent in Hispanics/Latinos. We tested whether all components significantly loaded on the syndrome in Hispanics/Latinos and whether their contribution differed by sex and Hispanic ancestry. We also examined associations of metabolic syndrome with prevalent diabetes and coronary heart disease (CHD) in Hispanics/Latinos

Correlates of Segmental Pulse Wave Velocity in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Carotid-femoral PWV (cfPWV) is a well-established measure of central arterial stiffness, while brachial-ankle PWV (baPWV) is being used more frequently in East Asian countries. Few studies have simultaneously characterized the distributions and correlates of segment-specific PWV measures and their associations with cardiovascular risk factors

Carotid Intima-Media Thickness and Incident ESRD: The Atherosclerosis Risk in Communities (ARIC) Study

Carotid intima-media thickness has been reported to predict kidney function decline. However, whether carotid intima-media thickness is associated with a hard kidney end point, ESRD, has not been investigated

Television, physical activity, diet, and body weight status: the ARIC cohort

<p>Abstract</p> <p>Background</p> <p>Television (TV) watching is the most common leisure activity in the United States. Few studies of adults have described the relationship between TV and health behaviors such as physical activity, diet, and body weight status.</p> <p>Methods</p> <p>Extant data from the Atherosclerosis Risk in Communities (ARIC) Study were analyzed to assess the association of TV with physical activity, diet, and body mass index (BMI) among 15,574 adults at baseline (1986–89) and 12,678 adults six years later. Television, physical activity, and diet were collected with questionnaires and BMI was measured at both time points. Based on baseline TV exposure, adults were categorized into high, medium, and low TV exposure. Linear and logistic regression models were adjusted for gender, age, race-center, smoking, education, and general health.</p> <p>Results</p> <p>Relative to participants who had low TV exposure, those with high TV exposure were more likely to be less physically active and have a poorer dietary profile at baseline and six-years later. Participants with high TV exposure at baseline had a 40% and 31% greater odds of being considered insufficiently active at baseline (1.40, 95% CI 1.26, 1.55), and six years later (1.31, 95% CI 1.18, 1.46). At baseline, high TV exposure was also associated with a 20% to 30% greater odds of being above the median for servings of salty snacks (1.37, 95% CI 1.24, 1.51), sweets (1.26, 95% CI 1.15, 1.38), and sweetened drinks (1.29, 95% CI 1.17, 1.42), and below the median for fruit and vegetable servings (1.36, 95% CI 1.24, 1.50). Higher TV exposure was also cross-sectionally associated with a greater odds for being overweight or obese (1.43, 95% CI 1.29, 1.58). Similar associations were observed between baseline TV exposure and six-year physical activity and diet, but were not observed with BMI after six years follow-up.</p> <p>Conclusion</p> <p>These results support the hypothesis that time spent watching TV is associated with deleterious effects on physical activity, diet, and BMI.</p

National Kriging Exposure Estimation: Liao et al. Respond

Szpiro et al. suggest that our findings Liao et al. (2006) do not adequately support using national-scale, log-normal ordinary kriging to estimate daily mean concentrations of PM10 (particulate matter with aerodynamic diameter ≤ 10 µm) at unmonitored locations in the contiguous United States. They posit that the absence of the cross-validation SE prevents evaluating the validity of kriging estimation, as we implemented in this context, and the comparability of both regionalversus national-scale kriging and manually modified versus semiautomated, defaultcalculated semivariograms