Abdominal obesity, blood glucose and apolipoprotein B levels are the best predictors of the incidence of hypercholesterolemia (2001–2006) among healthy adults: the ATTICA Study

<p>Abstract</p> <p>Objective</p> <p>In this work we evaluated the 5-year incidence of hypercholesterolemia, in a sample of cardiovascular disease free adult men and women from Greece. We also evaluated the association of several socio-demographic, dietary and lifestyle habits on the incidence of this disorder.</p> <p>Methods</p> <p>1514 men and 1528 women (>18 y) without any clinical evidence of cardiovascular disease, living in Attica area, Greece, were enrolled in the ATTICA study from May 2001 to December 2002. The sampling was random, multi-stage, and included information about various socio-demographic, lifestyle (diet, exercise, smoking etc), biological (lipids, and inflammatory markers), and clinical characteristics of the participants. In 2006, a group of experts performed the 5-year follow-up through telephone calls or personal visits (941 of the 3042 (31%) participants were lost to follow-up). Hypercholesterolemia, among people who had normal blood lipids at initial examination, was defined as fasting total cholesterol levels > 200 mg/dl or use of lipids lowering agents (NCEP ATPIII).</p> <p>Results</p> <p>The 5-year incidence of hypercholesterolemia was 23.7% (n = 127) in men and 17.7% (n = 110) in women (p for gender differences < 0.001). Multi-adjusted logistic regression analysis which revealed that increased age (odds ratio = 1.05, p < 0.001), waist circumference (odds ratio = 1.02, p = 0.03), fasting blood glucose (odds ratio = 1.01, p = 0.08) and apolipoprotein B (odds ratio = 1.02, p = 0.001) levels, were the most significant baseline predictors of developing hypercholesterolemia within a 5-year period.</p> <p>Conclusion</p> <p>Incidence of hypercholesterolemia was high in both genders, emphasizing the burden of this disorder at population level. Aging, increased waist circumference, fasting blood glucose and apolipoprotein B levels were the most significant baseline predictors of hypercholesterolemia.</p

Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma

Burn trauma results in prolonged hypermetabolism and skeletal muscle wasting. How hypermetabolism contributes to muscle wasting in burn patients remains unknown. We hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to muscle cachexia postburn. Patients (n = 14) with burns covering >30% of their total body surface area were studied. Controls (n = 13) were young healthy adults. We found that burn patients were profoundly hypermetabolic at both the skeletal muscle and systemic levels, indicating increased oxygen consumption by mitochondria. In skeletal muscle of burn patients, concurrent activation of mTORC1 signaling and elevation in the fractional synthetic rate paralleled increased levels of proteasomes and elevated fractional breakdown rate. Burn patients had greater levels of oxidative stress markers as well as higher expression of mtUPR-related genes and proteins, suggesting that burns increased mitochondrial stress and protein damage. Indeed, upregulation of cytoprotective genes suggests hypermetabolism-induced oxidative stress postburn. In parallel to mtUPR activation postburn, mitochondrial-specific proteases (LONP1 and CLPP) and mitochondrial translocases (TIM23, TIM17B, and TOM40) were upregulated, suggesting increased mitochondrial protein degradation and transport of preprotein, respectively. Our data demonstrate that proteolysis occurs in both the cytosolic and mitochondrial compartments of skeletal muscle in severely burned patients. Increased mitochondrial protein turnover may be associated with increased protein damage due to hypermetabolism-induced oxidative stress and activation of mtUPR. Our results suggest a novel role for the mitochondria in burn-induced cachexia