title: Protein concentration and mitochondrial content in the gastrocnemius predicts mortality rates in patients with peripheral arterial disease.
abstract: OBJECTIVE
  This study evaluated the hypothesis that protein concentration and mitochondrial content in gastrocnemius biopsies from patients with peripheral arterial disease (PAD) predict mortality rates.
  
  
  BACKGROUND
  PAD patients experience advancing myopathy characterized by mitochondrial dysfunction, myofiber degradation, and fibrosis in their ischemic legs, along with increased mortality rates.
  
  
  METHODS
  Samples from the gastrocnemius of PAD patients were used for all analyses. Protein concentration was normalized to muscle wet weight, and citrate synthase activity (standard measure of mitochondrial content in cells) was normalized to muscle wet weight and protein concentration. Protein and citrate synthase data were grouped into tertiles and 5-year, all-cause mortality for each tertile was determined with Kaplan-Meier curves and compared by the modified Peto-Peto test. A Cox-regression model for each variable controlled for the effects of clinical characteristics.
  
  
  RESULTS
  Of the 187 study participants, 46 died during a mean follow-up of 23.0 months. Five-year mortality rate was highest for patients in the lowest tertile of protein concentration. Mortality was lowest for patients in the middle tertile of citrate synthase activity when normalized to either muscle wet weight or protein concentration. The mortality hazard ratios (HRs) from the Cox analysis were statistically significant for protein concentration normalized to muscle wet weight (lowest vs middle tertile; HR = 2.93; P = 0.008) and citrate synthase normalized to protein concentration (lowest vs middle tertile; HR = 4.68; P = 0.003; and lowest vs highest tertile; HR = 2.36; P = 0.027).
  
  
  CONCLUSIONS
  Survival analysis of a contemporaneous population of PAD patients identifies protein and mitochondrial content of their gastrocnemius as predictors of mortality rate.
authors.affiliation: Departments of *Surgery and †Biostatistics, University of Nebraska Medical Center, Omaha, NE ‡Department of Surgery and VA Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE.
authors.forename: J R
authors.initials: JR
authors.lastname: Thompson
authors.forename: S A
authors.initials: SA
authors.lastname: Swanson
authors.forename: G
authors.initials: G
authors.lastname: Haynatzki
authors.forename: P
authors.initials: P
authors.lastname: Koutakis
authors.forename: J M
authors.initials: JM
authors.lastname: Johanning
authors.forename: P R
authors.initials: PR
authors.lastname: Reppert
authors.forename: E
authors.initials: E
authors.lastname: Papoutsi
authors.forename: D
authors.initials: D
authors.lastname: Miserlis
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: G P
authors.initials: GP
authors.lastname: Casale
authors.forename: I I
authors.initials: II
authors.lastname: Pipinos
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D005260:Female; D006801:Humans; D007484:Iowa; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism* / Q000401:mortality; D009329:Nebraska; D058729:Peripheral Arterial Disease / Q000378:metabolism* / Q000401:mortality*; D011237:Predictive Value of Tests; D015996:Survival Rate
chemical_list: D009124:Muscle Proteins