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Background: Accurate assessment of atherosclerotic cardiovascular disease (ASCVD) risk across heterogeneous populations is needed for effective primary prevention. Little is known about the performance of standard cardiovascular risk factors in older adults., Objective: To evaluate the performance of the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) risk model, as well as the underlying cardiovascular risk factors, among adults older than 65 years., Design and Setting: Retrospective cohort derived from a regional referral system's electronic medical records., Participants: A total of 25 349 patients who were 65 years or older at study baseline (date of the first outpatient lipid panel taken between 2007 and 2010)., Measurements: Exposures of interest were traditional cardiovascular risk factors, as defined by inclusion in the PCE model. The primary outcome was major ASCVD events, defined as a composite of myocardial infarctions, stroke, and cardiovascular death., Results: The PCE and internally estimated models produced similar risk distributions for white men aged 65 to 74 years. For all other groups, PCE predictions were generally lower than those of the internal models, particularly for African Americans. Discrimination of the PCE was poor for all age groups, with concordance index (95% confidence interval) estimates of 0.62 (0.60-0.64), 0.56 (0.54-0.57), and 0.52 (0.49-0.54) among patients aged 65 to 74, 75 to 84, and 85 years and older, respectively. Reestimating relationships within these age groups resulted in better calibration but negligible improvements in discrimination. Blood pressure, total cholesterol, and diabetes either were not associated at all or had inverse associations in the older age groups., Conclusion: Traditional clinical risk factors for cardiovascular disease failed to accurately characterize risk in a contemporary population of Medicare-aged patients. Among those aged 85 years and older, some traditional risk factors were not associated with ASCVD events. Better risk models are needed to appropriately inform treatment decision making for the growing population of older adults. J Am Geriatr Soc 68:754-761, 2020., (© 2020 The American Geriatrics Society.)

Importance: Immune dysregulation can increase the risk of infection, malignant neoplasms, and cardiovascular disease, but improved methods are needed to identify and quantify immunologic hazard in the general population., Objective: To determine whether lymphopenia is associated with reduced survival in outpatients., Design, Setting, and Participants: This retrospective cohort study of the National Health and Nutrition Examination Survey (NHANES) included participants enrolled from January 1, 1999, to December 31, 2010, a large outpatient sample representative of the US adult population. Associations were evaluated between lymphopenia and other immunohematologic (IH) markers, clinical features, and survival during 12 years of follow-up, completed on December 31, 2011. Spearman correlations, Cox proportional hazards regression models, and Kaplan-Meier curves were used in univariable and multivariable models, allowing for nonlinear associations with bivariate cubic polynomials. Data were analyzed from September 1, 2018, through July 24, 2019., Exposures: Absolute lymphocyte counts (ALC), red blood cell distribution width (RDW), and C-reactive protein (CRP) level., Main Outcomes and Measures: All-cause survival., Results: Among the 31 178 participants, the median (interquartile range) age at baseline was 45 (30-63) years, 16 093 (51.6%) were women, 16 260 (52.2%) were nonwhite, and overall 12-year rate of survival was 82.8%. Relative lymphopenia (≤1500/μL) and severe lymphopenia (≤1000/μL) were observed in 20.1% and 3.0%, respectively, of this general population and were associated with increased risk of mortality (age- and sex-adjusted hazard ratios [HRs], 1.3 [95% CI, 1.2-1.4] and 1.8 [95% CI, 1.6-2.1], respectively) due to cardiovascular and noncardiovascular causes. Lymphopenia was also associated with worse survival in multivariable models, including traditional clinical risk factors, and this risk intensified when accompanied by bone marrow dysregulation (elevated RDW) and/or inflammation (elevated CRP level). Ten-year mortality ranged from 3.8% to 62.1% based on lymphopenia status, tertile of CRP level, and tertile of RDW. A high-risk IH profile was nearly twice as common as type 2 diabetes (19.3% and 10.0% of participants, respectively) and associated with a 3-fold risk of mortality (HR, 3.2; 95% CI, 2.6-4.0). Individuals aged 70 to 79 years with low IH risk had a better 10-year survival (74.1%) than those who were a decade younger with a high-risk IH profile (68.9%)., Conclusions and Relevance: These findings suggest that lymphopenia is associated with reduced survival independently of and additive to traditional risk factors, especially when accompanied by altered erythropoiesis and/or heightened inflammation. Immune risk may be analyzed as a multidimensional entity derived from routine tests, facilitating precision medicine and population health interventions.