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  18th CROI
Conference on Retroviruses
and Opportunistic Infections
Boston, MA
February 27 - March 2, 2011
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Low Limb Muscle, High Visceral Fat Double 5-Year Risk of Death in US Cohort
  18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Low arm muscle, low leg muscle, and high visceral fat all independently raised the risk of 5-year all-cause mortality in the FRAM study group of US patient with HIV [1]. The FRAM researchers stressed that their findings may mean physicians are underestimating mortality risk in people with HIV because most rely on body mass index--not limb or visceral girth--as a tool to predict declining overall health.
The FRAM study was originally designed to distinguish abnormal fat changes in people with HIV from those in the general US population. The study group remains a useful source of clinical data, especially those involving fat measurements, which played a central role in the initial study. FRAM investigators decided to calculate the impact of limb and visceral fat on death risk because earlier studies in general populations found correlations between abnormally low limb fat and mortality.
The initial FRAM group included 1183 people, 794 of whom were alive 5 years later and 128 of whom had died 5 years later. The remaining 261 study participants stopped returning for clinic visits, and the researchers did not know whether they were living or dead.
FRAM investigators divided study participants into three even groups (tertiles) with the lowest arm muscle mass, midrange arm muscle mass, and the highest arm muscle mass. They also created leg mass and visceral fat tertiles. Compared with the highest arm muscle tertile, the lowest tertile had significantly fewer African Americans (30% versus 47%), significantly lower diabetes prevalence (6% versus 15%), significantly more current smokers (51% versus 37%), significantly lower systolic and diastolic blood pressure, significantly lower waist circumference (85 versus 93 cm), and significantly lower body mass index (22 versus 27 kg/m2) (P < 0.0001 for all differences). Median age in the three tertiles was equivalent at 42 to 43 years.
Multivariate analysis that adjusted for inflammation, kidney disease, and other death risk factors determined that being in the higher limb muscle tertiles lowered the risk of all-cause mortality over 5 years, while being in the higher visceral fat tertiles raised the risk of death at the following odds ratios (OR) (and 95% confidence intervals):
Compared with lowest arm muscle tertile:
Being in the middle tertile lowered the death risk 41%: OR 0.59 (0.35 to 0.99) Being in the high tertile lowered the death risk 49%: OR 0.51 (0.25 to 1.04, not significant))
Compared with lowest arm muscle tertile:
Being in the high tertile lowered the risk of death 58%: OR 0.42 (0.21 to 0.84)
Compared with lowest arm muscle tertile:
Being in the middle tertile raised the risk of death 77%: OR 1.77 (1.03 to 3.03) Being in the high tertile more than doubled the risk of death: OR 2.12 (1.13 to 3.98)
In a population-level analysis, being in the low arm muscle tertile raised the risk of death 15.1%, which translates into an additional 2 deaths per 100 persons over 5 years. Being in the lowest leg tertile raised the population-level death risk 7.2%, which translates into an additional 1 death per 100 persons over 5 years. And being in the highest visceral fat tertile raised the population-level risk of death 6.5%.
The FRAM investigators did not know causes of death. But because people with low limb fat and high visceral fat were less active physically, had more compromised kidney function, and included more smokers, they suggested many deaths had non-AIDS causes. The researchers do not believe missing data from people who dropped out of follow-up skewed their results because further analysis assuming various outcomes in these people did not change the main findings.
The researchers proposed that "a substantial proportion of this mortality risk may be unrecognized because of the current reliance on body mass index to assess wasting in clinical practice." They urged colleagues to measure waist circumference and midarm circumference in people with HIV and to "be aware that patients with excess central fat may not necessarily have a low enough body mass index to alert [the physician] to their true level of risk."
1. Scherzer R, Heymsfield S, Lee D, et al. Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 76.