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Does the impact of intensive lifestyle intervention on cardiovascular disease risk vary according to frailty as measured via deficit accumulation?
Simpson FR, Pajewski NM, Beavers KM, Kritchevsky S, McCaffery J, Nicklas BJ, Wing RR, Bertoni A, Ingram F, Ojeranti D, Espeland MA, for the Indices for Accelerated Aging in Obesity and Diabetes Ancillary Study of the Action for Health in Diabetes (Look AHEAD) Trial
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 2021 Feb;76(2):339-345
clinical trial
5/10 [Eligibility criteria: Yes; Random allocation: Yes; Concealed allocation: No; Baseline comparability: Yes; Blind subjects: No; Blind therapists: No; Blind assessors: No; Adequate follow-up: No; Intention-to-treat analysis: Yes; Between-group comparisons: Yes; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

BACKGROUND: Individuals are often counseled to use behavioral weight loss strategies to reduce risk for cardiovascular disease (CVD). We examined whether any benefits for CVD risk from weight loss intervention extend uniformly to individuals across a range of underlying health states. METHODS: The time until first occurrence of a composite of fatal and nonfatal myocardial infarction and stroke, hospitalized angina, or CVD death was analyzed from 8 to 11 years of follow-up of 4,859 adults who were overweight or obese, aged 45 to 76 years with type 2 diabetes. Individuals had been randomly assigned to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Participants were grouped by intervention assignment and a frailty index (FI) based on deficit accumulation, ordered from fewer (first tertile) to more (third tertile) deficits. RESULTS: Baseline FI scores were unrelated to intervention-induced weight losses and increased physical activity. The relative effectiveness of ILI on CVD incidence was inversely related to baseline FI in a graded fashion (p = 0.01), with relative benefit (hazard ratio 0.73 (95% CI 0.55 to 0.98)) for individuals in the first FI tertile to no benefit (hazard ratio 1.15 (0.94 to 1.42)) among those in the third FI tertile. This graded relationship was not seen for individuals ordered by age tertile (p = 0.52), and was stronger among participants aged 45 to 59 years (three-way interaction p = 0.04). CONCLUSIONS: In overweight/obese adults with diabetes, multidomain lifestyle interventions may be most effective in reducing CVD if administered before individuals have accrued many age-related health deficits. However, these exploratory analyses require confirmation by other studies. CLINICAL TRIAL REGISTRATION: NCT00017953.
Copyright the Gerontological Society of America. Reproduced by permission of the publisher.

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