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Heterogeneous exposure associations (HEAs) can be defined as differences in the association of an exposure with an outcome among subgroups that differ by a set of characteristics. In this article, we intend to foster discussion of HEAs in the epidemiologic literature and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association between systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989–1993), the Health, Aging, and Body Composition Study (1997–1998), and the Sacramento Area Latino Study on Aging (1998–1999). The test set included data from the National Health and Nutrition Examination Survey (1999–2002). The hazard ratios ranged from 1.25 (95% confidence interval: 1.13, 1.37) per 10-mm Hg increase in systolic blood pressure among men aged ≤67 years with diastolic blood pressure greater than 80 mm Hg to 1.00 (95% confidence interval: 0.96, 1.03) among women with creatinine concentration ≤0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations and guide the design of randomized controlled trials to control exposures in heterogeneous populations. [ABSTRACT FROM AUTHOR]

The US population aged 90 years or more is growing rapidly, and there are limited data on their health. The Cardiovascular Health Study is a prospective study of black and white adults aged ≥65 years recruited in 2 waves (1989–1990 and 1992–1993) from Medicare eligibility lists in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. We created a synthetic cohort of the 1,889 participants who had reached age 90 years at baseline or during follow-up through July 16, 2015. Participants entered the cohort at 90 years of age, and we evaluated their changes in health after age 90 years (median duration of follow-up, 3 years (interquartile range, 1.3–5)). Measures of health included cardiovascular events, cognitive function, depressive symptoms, prescription medications, self-rated health, and functional status. The mortality rate was high: 19.0 per 100 person-years (95% confidence interval : 17.8, 20.3) in women and 20.9 per 100 person-years (95% confidence interval: 19.2, 22.8) in men. Cognitive function and all measures of functional status declined with age; these changes were similar by sex. When we isolated period effects, we found that medication use increased over time. These estimates can help inform future research and can help health-care systems meet the needs of this growing population. [ABSTRACT FROM AUTHOR]

Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale proposed by Fried et al. has been the most widely used. We aimed to develop a continuous frailty scale that could overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (n = 4,243) and Health and Retirement Study (n = 7,600), both conducted in the United States. Frailty was conceptualized as a continuous construct, assessed by 5 measures used in the FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between the 5 indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across 2 cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and continued to be associated with outcomes among robust and prefrail persons classified by the FP scale. [ABSTRACT FROM AUTHOR]