Multiple morbidity complicates clinical decision-making and health policy. The prevention, diagnosis, and treatment of multiple diseases are burdensome, expensive, and potentially contradictory or harmful. Treating one disease may make other(s) worse. Furthermore, individuals with multiple diseases have varying health outcome priorities. Resolving these challenges and conflicts is difficult without a common metric to compare, contrast, and/or combine across diseases. The goal of this line of investigation, beginning with this exploratory study, will be to provide evidence supporting universal health outcomes as the unifying focus and common metric across chronic diseases. The purpose of this exploratory study is to determine whether disease-specific outcomes represent intermediates outcomes that mediate the effect of individual diseases on universal health outcomes. The primary aim is to determine, for individual chronic diseases, whether and to what extent disease-specific outcomes represent intermediate outcomes between the disease and one or more universal health outcomes. We will test the hypothesis that >50% of the effect of each of 4 diseases on one or more universal outcomes is mediated through the disease-specific outcomes. The secondary aim is to determine, for the combination of coexisting diseases, whether and to what extent disease-specific outcomes mediate the effect of the combination of coexisting diseases on universal health outcomes (this aim extends the primary aim by considering all 4 diseases together). We will address these aims in two longitudinal cohorts of older adults, the Women's Health and Aging Study I and ll and Cardiovascular Health Study. The chronic diseases include: heart failure, dementia, chronic lung disease, and arthritis. The universal outcome domains include: 1) Basic, instrumental, and social- productive activities of daily living;2) psychological functioning;3) cognitive functioning;4) symptom and impairment burden;and 5) survival /death. Finding that disease-specific outcomes map unto a universal set of health outcomes would support universal health outcomes as a common metric across diseases. If verified in future definitive studies, results of this line of investigation could ultimately inform clinical decision-making, research, and health policy. PUBLIC HEALTH RELEVANCE: The prevention, diagnosis, and treatment of multiple diseases are burdensome, expensive, and potentially contradictory or harmful. Resolving these challenges and conflicts is difficult without a common metric to compare, contrast, and/or combine across diseases. If disease-specific outcomes map unto a universal set of health outcomes, then these universal health outcomes could serve as common metrics across diseases that could inform clinical decision-making, research, quality assurance, and health policy.