Maren S. Fragala

The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates

Background. Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts. Methods. The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups. Results. The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [±6.1 SD] and in women 78.6 [±5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women. Conclusions. These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.

An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia

Background. Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia. Methods. The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed. Results. The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%). Conclusions. The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment.

Criteria for Clinically Relevant Weakness and Low Lean Mass and Their Longitudinal Association With Incident Mobility Impairment and Mortality: The Foundation for the National Institutes of Health (FNIH) Sarcopenia Project

Background. This analysis sought to determine the associations of the Foundation for the National Institutes of Health Sarcopenia Project criteria for weakness and low lean mass with likelihood for mobility impairment (gait speed ≤ 0.8 m/s) and mortality. Providing validity for these criteria is essential for research and clinical evaluation. Methods. Among 4,411 men and 1,869 women pooled from 6 cohort studies, 3-year likelihood for incident mobility impairment and mortality over 10 years were determined for individuals with weakness, low lean mass, and for those having both. Weakness was defined as low grip strength (<26kg men and <16kg women) and low grip strength-to-body mass index (BMI; kg/m2) ratio (<1.00 men and <0.56 women). Low lean mass (dual-energy x-ray absorptiometry) was categorized as low appendicular lean mass (ALM; <19.75kg men and <15.02kg women) and low ALM-to-BMI ratio (<0.789 men and <0.512 women). Results. Low grip strength (men: odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.34–3.99; women: OR = 1.99, 95% CI 1.23–3.21), low grip strength-to-BMI ratio (men: OR = 3.28, 95% CI 1.92–5.59; women: OR = 2.54, 95% CI 1.10–5.83) and low ALM-to-BMI ratio (men: OR = 1.58, 95% CI 1.12–2.25; women: OR = 1.81, 95% CI 1.14–2.87), but not low ALM, were associated with increased likelihood for incident mobility impairment. Weakness increased likelihood of mobility impairment regardless of low lean mass. Mortality risk patterns were inconsistent. Conclusions. These findings support our cut-points for low grip strength and low ALM-to-BMI ratio as candidate criteria for clinically relevant weakness and low lean mass. Further validation in other populations and for alternate relevant outcomes is needed.

Relationship between the number of repetitions and selected percentages of one repetition maximum in free weight exercises in trained and untrained men.

Resistance exercise intensity is commonly prescribed as a percent of 1 repetition maximum (1RM). However, the relationship between percent 1RM and the number of repetitions allowed remains poorly studied, especially using free weight exercises. The purpose of this study was to determine the maximal number of repetitions that trained (T) and untrained (UT) men can perform during free weight exercises at various percentages of 1RM. Eight T and 8 UT men were tested for 1RM strength. Then, subjects performed 1 set to failure at 60, 80, and 90% of 1RM in the back squat, bench press, and arm curl in a randomized, balanced design. There was a significant (p < 0.05) intensity × exercise interaction. More repetitions were performed during the back squat than the bench press or arm curl at 60% 1RM for T and UT. At 80 and 90% 1RM, there were significant differences between the back squat and other exercises; however, differences were much less pronounced. No differences in number of repetitions performed at a given exercise intensity were noted between T and UT (except during bench press at 90% 1RM). In conclusion, the number of repetitions performed at a given percent of 1RM is influenced by the amount of muscle mass used during the exercise, as more repetitions can be performed during the back squat than either the bench press or arm curl. Training status of the individual has a minimal impact on the number of repetitions performed at relative exercise intensity.

Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness

Background. Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s. Methods. In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment. Results. In men, a grip strength of 26–32 kg was classified as “intermediate” and less than 26 kg as “weak”; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.01–4.38) and 7.62 (95% CI 6.13–9.49), respectively. In women, a grip strength of 16–20 kg was classified as “intermediate” and less than 16 kg as “weak”; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.20–2.71) and 4.42 (95% CI 3.94–4.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure. Conclusions. Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function.

Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research

Purpose of reviewTo provide clinical investigators with an understanding of factors to consider when wishing to add cytokine and inflammatory marker measurements to their studies. Recent findingsInflammation involves complex and coordinated responses of the immune system to tissue damage. In the absence of tools to routinely assess inflammation within living tissues, measurements of humoral factors such as cytokines and other inflammatory mediators or markers can provide predictive clinical information and insights into disease mechanisms. Historically, enzyme-linked immunosorbent assays (ELISAs) became the gold standard, yet this approach of measuring a single protein in each sample limits the amount of information which can be obtained from limited amounts of human sample. In recent years, commercially available multiplex technologies which detect large numbers of proteins in a limited volume have provided investigators with opportunities to begin addressing the complexity of inflammatory responses. Nevertheless, great attention needs to be paid to many aspects of study design, sample collection, sample measurement and data analysis. These considerations are especially significant when using technologies for which experience remains limited. SummaryWhereas measurements of peripheral levels of inflammatory markers can add important mechanistic elements to human subject research, careful attention to conceptual and methodological considerations is essential, especially when using novel technologies.

Cutpoints for Low Appendicular Lean Mass That Identify Older Adults With Clinically Significant Weakness

Background. Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women). Methods. In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness. Results. In primary analyses, CART models identified cutpoints for low lean mass (ALM <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in men and ALMBMI <0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]). Conclusions. ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness.

EFFECTS OF A WHOLE BODY COMPRESSION GARMENT ON MARKERS OF RECOVERY AFTER A HEAVY RESISTANCE WORKOUT IN MEN AND WOMEN

Kraemer, WJ, Flanagan, SD, Comstock, BA, Fragala, MS, Earp, JE, Dunn-Lewis, C, Ho, J-Y, Thomas, GA, Solomon-Hill, G, Penwell, ZR, Powell, MD, Wolf, MR, Volek, JS, Denegar, CR, and Maresh, CM. Effects of a whole body compression garment on markers of recovery after a heavy resistance workout in men and women. J Strength Cond Res 24(3): 804-814, 2010-The primary purpose of this investigation was to evaluate the influence of a whole body compression garment on recovery from a typical heavy resistance training workout in resistance-trained men and women. Eleven men (mean ± SD: age, 23.0 ± 2.9 years) and 9 women (mean ± SD: age 23.1 ± 2.2 years) who were highly resistance trained gave informed consent to participate in the study. A within-group (each subject acted as their own control), balanced, and randomized treatment design was used. Nutritional intakes, activity, and behavioral patterns (e.g., no pain medications, ice, or long showers over the 24 hours) were replicated 2 days before each test separated by 72 hours. An 8-exercise whole body heavy resistance exercise protocol using barbells (3 sets of 8-10 repetition maximum, 2.0-to 2.5-minute rest) was performed after which the subject showered and put on a specific whole body compression garment one designed for women and one for men (CG) or just wore his/her normal noncompression clothing (CON). Subjects were then tested after 24 hours. Dependent measures included sleep quality, vitality rating, resting fatigue rating, muscle soreness, muscle swelling via ultrasound, reaction movement times, bench throw power, countermovement vertical jump power, and serum concentrations of creatine kinase (CK) measured from a blood sample obtained via venipuncture of an arm vein. We observed significant (p ≤ 0.05) differences between CG and CON conditions in both men and women for vitality (CG > CON), resting fatigue ratings (CG < CON), muscle soreness (CG < CON), ultrasound measure swelling (CG < CON), bench press throw (CG > CON), and CK (CG < CON). A whole body compression garment worn during the 24-hour recovery period after an intense heavy resistance training workout enhances various psychological, physiological, and a few performance markers of recovery compared with noncompressive control garment conditions. The use of compression appears to help in the recovery process after an intense heavy resistance training workout in men and women.

Influence of exercise order in a resistance-training exercise session.

The order of resistance exercises within a training session may have a vital impact on the quality of the constituent exercises performed. However, very few studies have documented the specific influence of exercise order. Therefore, the purpose of this study was to examine the effect of exercise order on back squat performance in the context of a whole-body workout. Nine resistance-trained male subjects (age: 24 ± 4 years, body mass: 81.5 ± 15.3 kg, resistance-training experience: 7 ± 4 years) performed the back squat exercise (4 sets at 85% of 1 repetition maximum) on 2 separate occasions in a balanced, crossover design. During one protocol, the squat exercise was performed first (protocol A); during the other protocol, it was performed after a whole-body resistance-exercise session (protocol B). Number of repetitions, average power, and rating of perceived exertion (RPE) were collected during each set of the squat exercise. All subjects performed significantly (p < 0.01) more repetitions during set 1 when they performed protocol A (8.0 ± 1.9 repetitions) compared with protocol B (5.4 ± 2.7 repetitions). The average power for each set was higher during protocol B compared with protocol A. There were no significant differences in RPE values between the 2 protocols. In conclusion, performing the barbell back squat first in an exercise session allowed the completion of more total repetitions. However, this study showed that performing the squat exercise after a whole-body workout session may result in greater power output if the squat is preceded by a power exercise (i.e., hang pull). This phenomenon may have been due to postactivation potentiation.

Effects of Stretching on Upper-body Muscular Performance

Torres, EM, Kraemer, WJ, Vingren, JL, Volek, JS, Hatfield, DL, Spiering, BA, Ho, JY, Fragala, MS, Thomas, GA, Anderson, JM, Häkkinen, K, and Maresh, CM. Effects of stretching on upper-body muscular performance. J Strength Cond Res 22: 1279-1285, 2008-The purpose of this investigation was to examine the influence of upper-body static stretching and dynamic stretching on upper-body muscular performance. Eleven healthy men, who were National Collegiate Athletic Association Division I track and field athletes (age, 19.6 ± 1.7 years; body mass, 93.7 ± 13.8 kg; height, 183.6 ± 4.6 cm; bench press 1 repetition maximum [1RM], 106.2 ± 23.0 kg), participated in this study. Over 4 sessions, subjects participated in 4 different stretching protocols (i.e., no stretching, static stretching, dynamic stretching, and combined static and dynamic stretching) in a balanced randomized order followed by 4 tests: 30% of 1 RM bench throw, isometric bench press, overhead medicine ball throw, and lateral medicine ball throw. Depending on the exercise, test peak power (Pmax), peak force (Fmax), peak acceleration (Amax), peak velocity (Vmax), and peak displacement (Dmax) were measured. There were no differences among stretch trials for Pmax, Fmax, Amax, Vmax, or Dmax for the bench throw or for Fmax for the isometric bench press. For the overhead medicine ball throw, there were no differences among stretch trials for Vmax or Dmax. For the lateral medicine ball throw, there was no difference in Vmax among stretch trials; however, Dmax was significantly larger (p ≤ 0.05) for the static and dynamic condition compared to the static-only condition. In general, there was no short-term effect of stretching on upper-body muscular performance in young adult male athletes, regardless of stretch mode, potentially due to the amount of rest used after stretching before the performances. Since throwing performance was largely unaffected by static or dynamic upper-body stretching, athletes competing in the field events could perform upper-body stretching, if enough time were allowed before the performance. However, prior studies on lower-body musculature have demonstrated dramatic negative effects on speed and power. Therefore, it is recommended that a dynamic warm-up be used for the entire warm-up.