Cardiovascular (CV) disease risk is increased in rheumatoid arthritis (RA) and is the leading cause of mortality. Improved CV risk stratification tools in RA could enhance use of preventative care and Show more
Cardiovascular (CV) disease risk is increased in rheumatoid arthritis (RA) and is the leading cause of mortality. Improved CV risk stratification tools in RA could enhance use of preventative care and improve outcomes. We previously studied biomarkers of CV disease - adiponectin, hsCRP, Lp(a), osteoprotegerin (OPG), high-sensitivity cardiac troponin T (hsTnT), serum amyloid A (SAA), YKL-40, soluble TNF receptor1 (sTNFR1) -- that were associated with CV risk. In the current study, these biomarkers were tested in an unrelated external cohort of RA patients followed at a single academic medical center without a history of CV events. CV events were identified through Medicare and Medicaid administrative data or through medical record review of self-reported events.Biomarkers were assessed at cohort entry among a nested cohort of cases and controls, matched 1:1 on sex and age. Analyses were conducted using conditional logistic regression. We examined whether the candidate biomarkers added to clinical CV risk factors improved model prediction, using the area under the curve (AUC) as well as the net reclassification index (NRI). From a cohort of 1,345 eligible patients with RA, we identified 123 patients with confirmed CV events. Cases and matched controls were typical of RA: median age 63 years, 77% women, RA disease duration 11 years, 72% seropositive, 85% used a biologic or conventional disease modifying anti-rheumatic drug, 58% non-steroidal anti-inflammatory drugs, and 30% oral glucocorticoids. From the candidate biomarkers, LASSO regression selected hsTnT and sTNFR1 as associated with CV events. The AUC for models that included only clinical risk factors was 0.758 (95% CI 0.689-0.829); after adding hsTnT and sTNFR1, the AUC increased to 0.802 (95% CI 0.718-0.998). The NRI of the model with biomarkers was 16.3%, with improvement only observed in patients who did not have CV events during follow-up. Adding selected biomarkers to clinical risk factors enhances the discrimination of models predicting CV events among patients with RA. These risk models require prospective testing to see if they have value in clinical practice decision-making regarding preventative care. Show less
We have previously identified predator odor as a potent stimulus activating thermogenesis in skeletal muscle in rats. As this may prove relevant for energy balance and weight loss, the current study i Show more
We have previously identified predator odor as a potent stimulus activating thermogenesis in skeletal muscle in rats. As this may prove relevant for energy balance and weight loss, the current study investigated whether skeletal muscle thermogenesis was altered with negative energy balance, obesity propensity seen in association with low intrinsic aerobic fitness, and monogenic obesity. First, weight loss subsequent to 3 wk of 50% calorie restriction suppressed the muscle thermogenic response to predator odor. Next, we compared rats bred based on artificial selection for intrinsic aerobic fitness - high- and low-capacity runners (HCR, LCR) - that display robust leanness and obesity propensity, respectively. Aerobically fit HCR showed enhanced predator odor-induced muscle thermogenesis relative to the less-fit LCR. This contrasted with the profound monogenic obesity displayed by rats homozygous for a loss of function mutation in Show less