IMPACT OF SIX MONTHS OF EXERCISE TRAINING ON SUBCLINICAL INFLAMMATION AND ENDOTHELIAL FUNCTION

Abstract

Purpose: Evidence has accumulated to show that elevated subclinical inflammation and impaired endothelial function has been associated with higher risk of cardiovascular disease (CVD). Despite data on these emerging risk factors, scant attention has been paid to: (1) the interactions of inflammation with endothelial function in relatively healthy African Americans; and (2) the efficacy of non-pharmacologic treatment modalities, such as exercise training, on inflammation and endothelial function. The aim of study 1 was to assess the levels of inflammatory markers, to assess the endothelial function in asymptomatic African Americans. The aim of study 2 was to determine the effects of six-months of exercise training on inflammatory markers and endothelial function in the same cohort. Methods: We recruited 79 African Americans who were sedentary, non-diabetic, non-smoking, and free of CV and renal disease. Before and after 6-month AEXT intervention, inflammatory markers (CRP, TNF-a and IL-6) were measured. Right brachial artery diameter was assessed at rest, during flow-mediated dilation (FMD), and after nitroglycerin-mediated dilation (NMD). Peak dilation was calculated as a measure of FMD and NMD, and the FMD/NMD ratio was calculated as a measure of endothelial function normalized by smooth muscle function. Fasted blood samples were obtained and were analyzed for the metabolic profile. Results: In study 1, the mean CRP for the group was 3.3 ± 0.3 mg/L which falls in the high-risk CRP category as per AHA/CDC guidelines. When divided into tertiles for CRP, low-risk (CRP 3 mg/L); VO2max was significantly higher in the low-risk category compared to average-risk category (P =0.004), and significantly higher in the low-risk category compared to high-risk category (P <0.001). Further, Cardiorespiratory fitness was significantly correlated with CRP (Figure. 1; r = -0.456, P <0.001) and BMI (r = -0.362, P = 0.002). CRP was correlated with BMI (r = 0.424, P <0.001). In a multivariable regression model that included age, gender, BMI, CVD risk factors (total cholesterol, triglycerides, HDL lipoprotein, LDL lipoprotein, plasma glucose, BP, and CRP), the following variables were significantly associated with fitness: fitness [B-coeff = -0.434 ± 0.05 (SE), P <0.001] independently predicted CRP. Fitness explained 22% of variance in CRP levels. In study 2, 6-month AEXT intervention significantly increased VO2max, (P=0.001), indicating that the prescribed exercise program may have been sufficient to elicit improvements in cardiovascular fitness. Significant reductions were observed for CRP (P =0.014). On repeated measures ANCOVA, the mean CRP values were significantly different (F (1,32) =6.703, P=0.014) between before vs. after training (Mean ± SEM; 3.1 ± 0.4 mg/L vs. 2.4 ± 0.4 mg/L), after adjusting for changed variables (BMI, mean BP and VO2max) as covariates. For endothelial measures, significant increase in endothelial function were observed for %FMDpeak (P =0.043) [Figure. 22] and FMD/NMD Ratio (P =0.047) increased post-AEXT. On repeated measures ANCOVA, the mean %FMD was statistically significantly different (F (1,16) =5.582, P=0.031) between before vs. after training (Mean ± SEM; 6.4 ± 2.6% vs. 9.4 ± 2.1%), after adjusting for changed variables (BMI, total-cholesterol and C-reactive protein) as covariates. Conclusions: The results from study 1 provide evidence of the prevalence of high levels of inflammation in the putatively healthy cohort of African Americans. When the group was categorized into tertiles for CRP and the cardio-metabolic, clinical and vascular profiles assessed, statistically significant differences, and rising trends were observed for CRP, body weight, BMI, BBF%, VO2max, SBP and DBP among the three CRP categories indicating a subclinical high cardiovascular risk profile in this cohort of putatively healthy population. Study 2, showed statistically significant improvements in inflammatory marker (CRP) and vascular measures (%FMDpeak, FMD/NMD Ratio and IMT); metabolic profile (triglycerides and FBS); clinical parameters (weight, BMI); cardiorespiratory fitness (VO2max). As we hypothesized, a marked reduction in CRP (-13.5%) post-AEXT was noticed, independent of change in(BMI, MAP and VO2max). Further, baseline CRP and BMI predicted change in CRP on regression analysis. Next, a marked increase in vascular measures, %FMDpeak (23.9%), FMD/NMD Ratio (25.4%) and IMT (-7.4%) were noticed independent of Ä(BMI, total cholesterol, MAP and VO2max). This may suggest: 1) the dominant anti-inflammatory role of exercise training. 2) that long-term exercise training improves clinical vascular measures in our cohort.