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Low muscle mass in HIV infected patients: prevalence, predictors and clinical implication: change in leg fat (surrogate for lipoatrophy) predicted low muscle mass, & low muscle mass predicts mortality; low muscle mass may be part of aging phenotype in HIV+
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle, WA
Guaraldi G1, Zona S1, Domingues da Silva Ana2, Orlando G1, Carli F1, Santoro A1, Crupi N1, Ligabue G1, Mussi C1, and Ferrucci L1
1University of Modena and Reggio Emilia, Italy - 2Hospital de Joaquim Urbano, Porto, Portugal - 2Research Branch National Institute on Aging (NIH), Baltimore, USA
in this study: "change in leg fat (surrogate for lipoatrophy) predicted low muscle mass, & low muscle mass predicts mortality...... The loss of both muscle mass and muscle strength defines sarcopenia, a geriatric syndrome associated with falls, hospitalization, institutionalization, disability and ultimately, mortality...... The anthropometric phenotype of HIV infected aging patients, with particular regards to skeletal muscle mass, will contribute to characterize the changing clinical picture of HIV disease from the pre-HAART era when wasting was the anthropometric paradigm of AIDS to the late-HAART era when sarcopenia may be the anthropometric paradigm of aging...... Fat Redistribution and Metabolic (FRAM) study found that, among HIV treated patients, 5-year mortality risks was associated with being in the highest tertile of VAT and with being in the lowest tertiles of leg or arm skeletal muscle mass, after the adjustment for other factors known to increase mortality."
Conclusion
· The main result of this study goes beyond the confirmation that FFMi is an independent predictor of all cause mortality, but rather supports the use of LMM (FFMi Z-score <-2 SD) as a biological entity that can be used in clinical setting to predict all cause mortality
· Prevalence of LLM [low muscle mass] (FFMi Z-score < -2 SD) was appreciable in all age strata qualifying this variable for clinical use.
· In a large sample (1877) of subjects we provide gender and age related percentile for FFMi.
· FFMi in absolute terms appeared to be constant across age groups, both in men and in women.
·· FFMi changes appear to be related to time between DXA and leg fat percent. Leg fat % is a surrogate for lipoatrophy. Its increase over time may describe the reversibility of lipoatrophy observed in the late HAART era
· During the period of observation 37 patients died. LLM is an independent predictor of all cause mortality
Main limitations
· This is an observational study. The methodology of our study implies the possibility that a survival bias may have occurred. We cannot exclude that patients with better prognosis were "selected out", especially in the more advanced age group categories.
ABSTRACT
Background
In HIV infected patients (pts), muscle mass measured as fat free mass index (FFMi=FFM/h2) in DXA has never been characterized in large epidemiological cohorts.
We aimed to: 1.describe the prevalence of Low muscle mass (LMM) using t and z-score, per age decades, defined as <-2 SD from the mean FFMi for Italian caucasian population, respectively for same age or in the age strata 30-39 years; 2.identify predictors of FFMi change 3.assess the association between FFMi and all cause mortality in a large HIV cohort.
Methods
Observational prospective study including all consecutive pts from 2005 to 2011 who underwent at least 2 DXA scans, performed 1 year apart. Univariate and multivariable longitudinal linear regressions were built to evaluate FFMI change associated factors. Covariates included in the models were: age, sex, BMI, physical activity, change in leg fat % (assessed with DXA), change in Visceral adipose tissue (VAT) and in Total adipose tissue of the abdomen (TAT) (assessed with abdominal CT), NRTI, NNRTI and PI cumulative exposure, CD4 nadir, CD4 recovery from nadir, VitD plasma level, time between DXA scans.
A Cox model was built to predict the impact of FFMi on all cause mortality after adjustment for age and sex.
Results
A total of 1877 HIV-infected patients (1239 men and 638 women). Median observation follow-up period was 3.5 years (IQR 2; 5). 96% of pts were on ART. During the follow up period 37 pts died.
BMI change and FFMI change appeared stable over time (ß=0.001, p=0.111; ß=0.001, p=0.070 respectively).
1. In men the prevalence of LMM using T and Z-score was 0.2% and 8.5%, respectively. In women the prevalence of LMM using t and z-score was 0% and 1.5%, respectively. The highest prevalence of LMM was detected in the 41-50 age group strata (T-score 0.5% and Z-score 16%).
2. Predictors of FFMi change were: age (ß=-0.01, p=0.005), change of leg fat% (as a surrogate for lipoatrophy recovery) (ß=-0.05, p<0.001), and time between DXA scans (ß=0.17, p=0.013).
3. FFMi was associated to all cause mortality (HR = 0.87; 95% CI 0.78-0.98) after adjustment for age and sex.
Discussion
Prevalence of LMM increases with age.
The highest prevalence was found in the 41-50 age group. Predictors of FFMi change appear to be associated with age, lipoatrophy recovery and time.
FFMi is associated with all cause mortality in HIV infected pts, suggesting that this biological entity can provide prognostic information, in HIV infected pts.
BACKGROUND
In the general population a 60 to 85% increase of fat mass, predominantly represented by visceral adiposity (VAT), is expected between 25 and 65 years of age; in the same period there is a 20% decline of skeletal muscle mass. These body composition changes are key determinants of ageing phenotype, being constant across all ethnicities.
The loss of both muscle mass and muscle strength defines sarcopenia, a geriatric syndrome associated with falls, hospitalization, institutionalization, disability and ultimately, mortality.
The anthropometric phenotype of HIV infected aging patients, with particular regards to skeletal muscle mass, will contribute to characterize the changing clinical picture of HIV disease from the pre-HAART era when wasting was the anthropometric paradigm of AIDS to the late-HAART era when sarcopenia may be the anthropometric paradigm of aging.
In clinical trials skeletal muscle mass is measured with DXA after adjustment for height. This define Fat free mass index (FFMi=FFM/h2), which allows a correction of the amount of lean mass by height (as BMI).
So far the clinical impact of low FFMi in HIV infected patients is still to be determined. Fat Redistribution and Metabolic (FRAM) study found that, among HIV treated patients, 5-year mortality risks was associated with being in the highest tertile of VAT and with being in the lowest tertiles of leg or arm skeletal muscle mass, after the adjustment for other factors known to increase mortality.
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