Is obesity predictive of cardiovascular dysfunction independent of cardiovascular risk factors?

INTRODUCTION: Obesity is thought to exert detrimental effects on the cardiovascular (CV) system. However, this relationship is impacted by the co-occurrence of CV risk factors, type 2 diabetes (T2DM) and overt disease. We examined the relationships between obesity, assessed by body mass index (BMI) and waist circumference (WC), and CV function in 102 subjects without overt CV disease. We hypothesized that obesity would be independently predictive of CV remodeling and functional differences, especially at peak exercise. METHODS: Brachial (bSBP) and central (cSBP) systolic pressure, carotid-to-femoral pulse wave velocity (PWVcf) augmentation index (AGI; by SphygmoCor), and carotid remodeling (B-mode ultrasound) were examined at rest. Further, peak exercise cardiac imaging (Doppler ultrasound) was performed to measure the coupling between the heart and arterial system. RESULTS: In backward elimination regression models, accounting for CV risk factors, neither BMI nor WC were predictors of carotid thickness or PWVcf; rather age, triglycerides and hypertension were the main determinants. However, BMI and WC predicted carotid cross-sectional area and lumen diameter. When examining the relationship between body size and SBP, BMI (ß=0.32) and WC (ß=0.25) were predictors of bSBP (P<0.05), whereas, BMI was the only predictor of cSBP (ß=0.22, P<0.05) indicating a differential relationship between cSBP, bSBP and body size. Further, BMI (ß=-0.26) and WC (ß=-0.27) were independent predictors of AGI (P<0.05). As for resting cardiac diastolic function, WC seemed to be a better predictor than BMI. However, both BMI and WC were inversely and independently related to arterial-elastance (net arterial load) and end-systolic elastance (cardiac contractility) at rest and peak exercise. CONCLUSION: These findings illustrate that obesity, without T2DM and overt CV disease, and after accounting for CV risk factors, is susceptible to pathophysiological adaptations that may predispose individuals to an increased risk of CV events.

Effects of downhill treadmill running on uncoupling protein 3 mRNA expression.

Eccentric biased exercise has been reported to elicit more muscle injury than concentric or isometric exercise and potentially generate increased oxidative stress one to two days post exercise. Increased oxidative stress has been shown to up-regulate the expression of UCP3 mRNA. The aim of this study was to investigate the effects of downhill running on skeletal muscle UCP3 mRNA expression. Twenty-four male Sprague Dawley rats were randomly assigned to run continuously for 30 minutes (30-C, n = 6), or run six 5-minute bouts separated by rest periods of 2 minutes (2-R, n = 6), 4 minutes (4-R, n = 6), and 6 minutes (6-R, n = 6) on a 16 degree declined treadmill at a speed of 16 m. min (-1). Sham control animals (n = 8) were placed in a treadmill chamber during the 30-minute run session. Semi-quantitative RT-PCR was conducted to evaluate UCP3 mRNA levels in the plantaris, a muscle used eccentrically during downhill running and tibialis anterior, a muscle which undergoes very little eccentric muscle contraction during this exercise. The level of gene expression was normalized to 18 S ribosomal mRNA expression from the same PCR product. Results are reported as mean +/- standard error. UCP3 of the plantaris muscles from 2-R animals (2.36 +/- 0.13) was significantly greater than UCP3 of the plantaris from control animals (1.72 +/- 0.13), p < 0.05. UCP3 of the tibialis anterior from the continuous group (1.51 +/- 0.17) was significantly less than the UCP3 of the tibialis anterior of the control group (2.09 +/- 1.4), p < 0.05. These data suggest that downhill treadmill running is associated with an increase in UCP3 mRNA expression in the plantaris muscle. These results indicate that exercise which is biased toward eccentric exercise may up-regulate UCP3 mRNA during the period post exercise when muscle damage and repair is elevated.