Physical Function: Overview Definition: ability to perform physical activities without assistance. Dependent on: physical fitness (strength & stamina) functional ability (coordination, balance) Measured by: 1.)performance-based tests: “functional performance” lab-based, objective Grip strength, timed walking 2.) self report Ability within home environment and social context

Make 4 bar graphs for gair speed and chair stand, check how cutoffs defined Functional Performance Predicts Mortality and Hospitalization In HIV Negative Elderly Adults Health, Aging and Body Composition Study, N= 3,079, aged 70-79 Cesari M, JAGS, 2009

Comparison of Functional Performance in HIV + vs Healthy Men N= 346 (Lindle RS, J Appl Physiol 1997) mean age, 52; median= same, 30-81 Oursler, KK, 2006

Functional Performance (N=56) Correlates with VACS Risk Index Score table score_cat, contents( mean _6MWm mean gpdomin mean AGE ) ------------------------------------------------------- 1,<30; | 2,30-49; | 3, | 50-64;4, | 65+ | mean(_6MWm) mean(gpdomin) mean(AGE) ----------+-------------------------------------------- 1 | 564.2402 43.14394 49.33329 2 | 517.9187 39.61806 54.76199 3 | 519.8364 33.61111 54.93251 4 | 437.5912 37.05556 60.34977 for VO2peak, r= -0.31, p=0.02 Lowest quartile of grip strength associated with 7.5 point higher median score than highest quartile Decrease of 50 meters associated with 33 point increase in score

Mild anemia is associated with reduced 6-MWD add data values and p values, walking speed ref . ttest vo2_kg if study==1, by( hct35) ----------------------------------------------------------------------------- Group | Obs Mean Std. Err. Std. Dev. [95% Conf. Interval] ---------+-------------------------------------------------------------------- 0 | 49 21.09306 .8028699 5.620089 19.47878 22.70734 1 | 9 17.35556 2.060752 6.182255 12.60345 22.10766 combined | 58 20.5131 .7636782 5.816 18.98386 22.04234 diff | 3.737506 2.068514 -.4062251 7.881236 ------------------------------------------------------------------------------ Pr(T < t) = 0.9619 Pr(|T| > |t|) = 0.0762 Pr(T > t) = 0.0381 . ttest _6MWm if study==1, by( hct35) 0 | 49 543.6201 10.84777 75.93439 521.8092 565.431 1 | 9 465.5651 26.52529 79.57588 404.3976 526.7325 combined | 58 531.5081 10.63263 80.97572 510.2167 552.7996 diff | 78.05506 27.73056 22.50408 133.6061 Ha: diff < 0 Ha: diff != 0 Ha: diff > 0 Pr(T < t) = 0.9966 Pr(|T| > |t|) = 0.0067 Pr(T > t) = 0.0034

Comparison of Survey Items

Self-reported Function in MACS 1994-1996 Hiv neg: hiv + 42 yrs(37-47) 39 (35-45) median (range) white 89% 83% jacobson and fried looked at self -reported measures… they found that hiv infected more likley to have each one of the characteristics of fraily than hiv negative men , and when frailty was defined as presence of 3 or more characteristics, 10 fold increase in the hiv-infected men since wasting can be important manifestation of AIDS, separate models that excluded subjects with weight loss, and still found that hiv-infected had 4 fold increased risk frailty prevalence- Increased by duration of HIV infection Increased by age, OR 1.6 (1.2, 2.2) 55 yo men with HIV for < 4 years have an est. prevalence of frailty of 3.4% = 65+ yo men without HIV * age, ethnicity, education Total number frail: HIV-infected (n=245) vs. HIV-negative men (n=1905) Update ref Check time parameters &if have survival Desquilbert, Jacobson, Fried, et al, in press, J Gerontology Med Sci

Self-reported Physical Function in VACS: Limitations and Mean VACS Index Score by Item HIV + Only, N= 2772 Yes Slowly No

VACS Physical Function Score Sum of 12 survey items Transformed to 100 scale Ceiling effect: 1/3 subjects no limitations % Histogram for HIV + N= 2772

VACS Physical Function Score Sum of 12 survey items Transformed to 100 scale Ceiling effect: 1/3 subjects no limitations  Three groups: Severe limitations base on Lowest quintile (<67) % Histogram for HIV + N= 2772

VACS Physical Function Score Sum of 12 survey items Transformed to 100 scale Ceiling effect: 1/3 subjects no limitations  Three groups: Severe limitations base on Lowest quintile (<67) Intermediate limitations (68-99) % Histogram for HIV + N= 2772

VACS Physical Function Score Sum of 12 survey items Transformed to 100 scale Ceiling effect: 1/3 subjects no limitations  Three groups: Severe limitations base on Lowest quintile (<67) Intermediate limitations (68-99) No limitations (=100) % Histogram for HIV + N= 2772

Level of Function Associated with VACS Index VACS Risk Index Score 40 35 30 25 20 15 Small note on distribution, cut off of 67 in this limited dataset (hiv = only and those with the vacs index score available, actually is 23%, not 20% N =3280 BACS-8 HIV + function group N =2772 for sub-set with index available 10 5 severe limitations intermediate limitations no limitations N = 650 N = 1094 N = 1028 need p value?

intermediate limitations no limitations intermediate limitations severe limitations HR= 1.8 (1.4,2.2) HR= 3.0 (2.4,3.8) 2,<67, | 0, censured; 1, died 20%centile | 0 1 | Total -----------+----------------------+---------- 0 | 1,021 123 | 1,144 1 | 997 225 | 1,222 2 | 529 212 | 741 Total | 2,547 560 | 3,107 . xi: stcox i.functlevel if HIV==1 i.functlevel _Ifunctleve_0-2 (naturally coded; _Ifunctleve_0 omitted) failure _d: death analysis time _t: time_yrs Refining estimates: Iteration 0: log likelihood = -4327.727 Cox regression -- Breslow method for ties No. of subjects = 3101 Number of obs = 3101 No. of failures = 560 Time at risk = 14292.49315 LR chi2(2) = 99.85 Log likelihood = -4327.727 Prob > chi2 = 0.0000 ------------------------------------------------------------------------------ _t | Haz. Ratio Std. Err. z P>|z| [95% Conf. Interval] -------------+---------------------------------------------------------------- _Ifunctlev~1 | 1.788661 .2005984 5.18 0.000 1.435707 2.228385 _Ifunctlev~2 | 3.018998 .3422996 9.75 0.000 2.417419 3.77028 adjusted for agebl, sex, raceg level01 1.6 (1.3, 2.0) level02 2.7 (2.2, 3.4)

HIV and Pulmonary Disease Together Severely Affect Function 65 70 75 80 85 90 35 40 45 50 55 60 Function Score HIV- Pulm- HIV+ Pulm- HIV- Pulm+ HIV+ Pulm+ Age (yr)

Take Home Points Self-reported measures need to: have wider dynamic range Functional performance measures need to: measure different parameters endurance rather than slowing lower extremity muscle wasting + central obesity ? be adapted for impact of specific comobidities anemia, lung disease, diastolic dysfunction

Ongoing Physical Function Research in VACS Change in function score over time Cardiac and pulmonary predictors of performance in 6 MWD INHALE (PI, Crothers) VACS ABC (PI, Freidberg) Proposal to study relationship of cardiac function and exercise performance

Reference slides

6MWD appears to be sensitive measure of exercise capacity add data values and p values, r value b/w 2 . ttest vo2_kg if study==1, by( hct35) ----------------------------------------------------------------------------- Group | Obs Mean Std. Err. Std. Dev. [95% Conf. Interval] ---------+-------------------------------------------------------------------- 0 | 49 21.09306 .8028699 5.620089 19.47878 22.70734 1 | 9 17.35556 2.060752 6.182255 12.60345 22.10766 combined | 58 20.5131 .7636782 5.816 18.98386 22.04234 diff | 3.737506 2.068514 -.4062251 7.881236 ------------------------------------------------------------------------------ Pr(T < t) = 0.9619 Pr(|T| > |t|) = 0.0762 Pr(T > t) = 0.0381 . ttest _6MWm if study==1, by( hct35) 0 | 49 543.6201 10.84777 75.93439 521.8092 565.431 1 | 9 465.5651 26.52529 79.57588 404.3976 526.7325 combined | 58 531.5081 10.63263 80.97572 510.2167 552.7996 diff | 78.05506 27.73056 22.50408 133.6061 Ha: diff < 0 Ha: diff != 0 Ha: diff > 0 Pr(T < t) = 0.9966 Pr(|T| > |t|) = 0.0067 Pr(T > t) = 0.0034

Change in Physical Function with Aging: a Moving Target VO2peak (ml/kg/min) Aerobic Capacity Injury Age (yrs) 50 60 70 80 Rehabilitation Nursing Home Death Normal Aging 40 30 Recovery 20 Chronic Disability  HIV   Stroke CHF

Implications for Life Expectancy Beyond Survival: Implications for Life Expectancy Adapted from theory of compression of morbidity theory from James F. Fries Stanford University, Palo Alto, California Fries, NEJM 1980 (his theory - ave period disabled life will decrease) Oursler, 2007

Frailty Phenotype in Elderly HIV uninfected Relatively uncommon. Among 70-79yo: 12% of Cardiovascular Health Study (CHS) 11.3% of WHAS (Women’s Health and Aging Study) I & II cohort A Clinical Syndrome, present if 3/5 +: Exhaustion (self- report) Slowed walking speed (4-8 m walk) Low activity (self-report) Weakness (lowest quintile grip strength) Weight loss (self-report and measured) Check refs Fried L, et al. J of Gerontology, 2001 Newman, et al. J of Gerontology, 2001 Bandeen-Roche et al. , J of Gerontology, 2006

Mean VACS Index Score by Survey Item

Self reported physical limitations VACS 8 (N =3280) Yes Slowly No Response