Chair rise rate was calculated as the number of chair stands performed divided by the time to complete 10 chair stands. Participants unable to attempt the test were assigned the worst time (9 seconds/stand for every stand not done). Linear mixed effects models for repeated measures were used to estimate annualized rate of change (slope), and the difference between treatment groups (interaction between slope and treatment group). Negative annualized rate of change reflects decline over time, positive improvement over time.

All participants enrolled with any chair rise rate data available.

Conditional on the positive findings on the primary physical function, the IIS score will be calculated as 1/3 log [interleukin-6 (IL-6)] + 2/3 log [soluble tumor necrosis factor receptor 1 (sTNFR-1)] using specimens collected as part of the main study REPRIEVE, and used to evaluate mechanistic pathways through which pitavastatin affects physical function.

The specimen testing was not performed.

Paraspinal muscle (a back muscle) density was measured in Hounsfield units (HU, lower values indicate fattier muscle) from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE. HU are used to measure the radiation attenuation of muscle in CT scans. Muscle tissue was identified as voxels with attenuation of -190 HU (very low density muscle, the fattiest) to 100 HU (high density muscle, the leanest).

Participants who remained on study treatment at Month 24 (per-protocol set) and had data for this outcome available at both baseline and month 24.

Gait speed was calculated as 4 meters divided by the average time to complete the 4-meter walk. Participants unable to attempt the test were assigned the worst gait speed (0 meters/second). Linear mixed effects models for repeated measures were used to estimate annualized rate of change (slope), and the difference between treatment groups (interaction between slope and treatment group). Negative annualized rate of change reflects decline over time, positive improvement over time.

All participants enrolled with any gait speed data available.

Grip strength was calculated as the average of three measurements in the dominant hand by Jamar Hydraulic Hand Dynamometer. Participants unable to attempt the test were assigned the worst result (0 kg). Linear mixed effects models for repeated measures were used to estimate annualized rate of change (slope), and the difference between treatment groups (interaction between slope and treatment group). Negative annualized rate of change reflects decline over time, positive improvement over time.

All participants enrolled with any grip strength data available.

Physical function impairment according to balance was defined as inability to hold single-leg stand for 30 seconds. Annualized risk of impairment year-over-year (ratio of risk per year, compared to risk per previous year) was estimated using log-binomial regression models for repeated data using GEE (relative risk of >1 reflects an increase in risk compared to previous year, relative risk <1 a decrease in risk compared to previous year). GEE (generalized estimating equations) is a statistical method for analyzing repeated measures, such as measurements of the outcome in participants at multiple time points.

All participants enrolled with any balance data available.

Modified SPPB score (on scale from 0-worst to 3-best) was calculated as a sum of the following components each divided by the maximal possible performance: (1) chair rise rate (stands/second) divided by maximal performance of one stand/second; (2) proportion of total standing balance time calculated as the total time each of the semi-tandem, tandem and one-leg stand positions were held (maximum 30 seconds each) divided by 90 seconds; and (3) gait speed (meters/second) based on average of the 4-meter walk results divided by maximal performance of 2 meters/second. Linear mixed effects models for repeated measures were used to estimate annualized rate of change (slope), and the difference between treatment groups (interaction between slope and treatment group). Negative annualized rate of change reflects decline over time, positive improvement over time.

All participants enrolled with any mSPPB data available.

Physical function impairment according to composite Short Physical Performance Battery (SPPB, consisting of repeated chair stands, balance and gait speed tests) was defined as score <=10. In the absence of trend over time, average relative risk of impairment over follow-up time (ratio) was estimated using log-binomial regression models for repeated data using GEE (relative average risk of >1 reflects an increase in risk over follow-up time, relative average risk <1 a decrease in risk over follow-up time). GEE (generalized estimating equations) is a statistical method for analyzing repeated measures, such as measurements of the outcome in participants at multiple time points.

All participants enrolled with any SPPB data available.

Impairment was classified according to self-administered Duke Activity Status Index questionnaire score (on scale from 0-worst to 58.2-best) as no impairment (the max score of 58.2), some impairment (score of 34.7-<58.2), moderate impairment (9.95-<34.7) and severe impairment (0-<9.95).

All participants enrolled with DASI questionnaire completed at the given time point.

Frailty Phenotype was defined based on the following components: (1) weight loss (self-report of unintentional weight loss of 10 or more pounds in the prior year), (2) exhaustion (experiencing at least three to four times per week the feeling that "everything I do is an effort" or "sometimes I cannot get going", (3) low physical activity (being "limited a lot" in response to the Short Form 36 question "does your health limit you in vigorous activities such as running, lifting heavy objects, or participating in strenuous sports?", (4) slow gait by average of two 4-meter walk times, and (5) weak grip by average of three measurements on a handheld Jamar dynamometer. Participants were classified as non-frail if they had no components present, pre-frail with one or two components present, and frail with three or more components present.

All participants enrolled with frailty phenotype data available. (Data availability at baseline and 12 depends on timing of PREPARE enrollment relative to REPRIEVE enrollment.)

Self-reported physical activity evaluated by the questionnaire "Rapid Eating and Activity Assessment for Patients" (REAP) question 27: In an average week, how often do you do <30 minutes of physical activity 3 or more days a week?

All participants enrolled with REAP Question 27 data available.

Self-reported physical activity evaluated by the questionnaire "Rapid Eating and Activity Assessment for Patients" (REAP) question 28: In an average week, how often do you do watch >2 hours of TV or videos a day?

All participants enrolled with REAP Question 28 data available.

Pectoral (a chest muscle) density was measured in Hounsfield units (HU) from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE.

Participants who remained on study treatment at Month 24 (per-protocol set) and had data for this outcome available at both baseline and month 24.

Infraspinatus (an upper back muscle) density was measured in Hounsfield units (HU) from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE.

Participants who remained on study treatment at Month 24 (per-protocol set) and had data for this outcome available at both baseline and month 24.

Paraspinal muscle (a back muscle) area was measured from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE.

Participants who remained on study treatment at Month 24 (per-protocol set) and had data for this outcome available at both baseline and month 24.

Pectoral muscle (a chest muscle) area was measured from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE.

Participants who remained on study treatment at Month 24 (per-protocol set) and had data for this outcome available at both baseline and month 24.

Infraspinatus muscle (an upper back muscle) area was measured from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE.

Participants who remained on study treatment at Month 24 (per-protocol set) and had data for this outcome available at both baseline and month 24.

Conditional on the positive findings on the primary physical function, select biomarkers including each individual biomarker of the IIS (IL-6, sTNFR-1) as well as other biomarkers implicated in the pathogenesis of physical function impairment or those that may mediate the effects of statins on systemic inflammation will be used to evaluate mechanistic pathways through which pitavastatin affects physical function. The specific list of biomarkers of interest will be finalized closer to the time of analysis, incorporating the developments in the field over the few years from study development to completion.

The specimen testing was not done.