SUMMARY: HIV positive people who lose muscle in their arms and legs while gaining abdominal fat are at increased risk of death, according to findings from the FRAM study presented at CROI 2011.

By Liz Highleyman

Unintended weight loss and loss of lean muscle mass are known risk factors for mortality in people with a variety of disease conditions. Although there have been many studies of body fat changes among people with HIV, less is known about changes in muscle mass.

Rebecca Scherzer from the University of California at San Francisco presented data this month at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) from an analysis of changes in muscle, subcutaneous fat, and abdominal or central fat, which reflects visceral fat around the internal organs.

The investigators performed whole-body magnetic resonance imaging (MRI) on nearly 1200 HIV positive participants in the ongoing FRAM study (Fat Redistribution and Metabolic Change in HIV Infection). About two-thirds were men, about 50% were white, about 40% were African-America, and the average age was slightly over 40 years. The mean body mass index (BMI) was about 25, just at the threshold for classification as "overweight."

Results

	Over 5 years of follow-up, decreased muscle mass in the arms and legs was a strong predictor of all-cause mortality.
	Increased abdominal fat also strongly predicted mortality.
	These associations held up after controlling for potential confounding factors including demographics, cardiovascular risk, CD4 cell count, HIV viral load, kidney disease, and inflammation biomarkers.
	After controlling for such factors, people in the lowest tertile (third) of arm muscle mass had a 2-fold higher risk of death than those in the highest tertile (odds ratio 0.51 for highest vs lowest).
	People in the lowest leg muscle tertile approached twice the risk of death (OR 0.42 highest vs lowest), but being in the middle tertile conferred no added risk.
	Participants in the highest abdominal/visceral fat tertile also had about double the risk of death (OR 2.1 highest vs lowest).
	Being in the lowest arm muscle mass tertile was calculated to account for 15.1% of excess mortality among people with HIV -- about 2 additional deaths over 5 years.
	Being in the lowest leg muscle tertile accounted for 7.2% of excess mortality, or 1 additional death.
	Being in the highest abdominal fat tertile accounted for 6.5% of excess mortality.
	Loss of fat in the arms and legs (peripheral lipoatrophy), however, was not significantly associated with higher mortality.

Based on these findings, the FRAM investigators concluded, "Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals."

But measuring BMI may underestimate this risk, Scherzer explained at a CROI press conference. BMI -- calculated as body weight divided by height squared -- is often used as a surrogate measure for body fat, but people who have both excess abdominal fat and reduced limb muscle mass may have a BMI within the normal range.

"BMI is a flawed measure that can classify people with a lot of muscle as obese," she said. Conversely, "people with large bellies may not have a high enough BMI to alert [us] to risk status" if they also have low limb muscle mass.

Instead of relying on BMI, she recommended, clinicians should measure waist circumference as a simple indicator of visceral fat, as well as mid-arm muscle mass, which can be estimated using mid-arm circumference and triceps skin-fold thickness.

Investigator affiliations: Univ of California, San Francisco, CA; San Francisco VAMC, San Francisco, CA; Pennington Biomed Research Ctr, Baton Rouge, LA; Univ of California, San Diego, CA; Univ College Dublin School of Medicine and Med Sci, Dublin, Ireland.

3/22/11

Reference
R Scherzer, S Heymsfield, D Lee, 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 (CROI 2011). Boston. February 27-March 2, 2011. Abstract 36.