Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.

ABSTRACT Despite significant advancements in drug therapy, cardiovascular disease (CVD) is still the leading cause of death in the United States. Given this, research has begun to seek out alternative approaches to reduce CVD risk. One of these alternative approaches is Vitamin D supplementation. Current research has shown a link between Vitamin D status and CVD risk in both healthy and diseased populations. Among the possible mechanisms is a positive effect of Vitamin D on vascular endothelial function, which can be measured with noninvasive techniques such as flow-mediated dilation (FMD) of conduit vessels using high-resolution ultrasound. This dissertation is comprised of two studies. The first examines whether Vitamin D supplementation can improve FMD in older adults within a time period (two weeks) associated with peak increases in plasma Vitamin D concentrations after a single-dose supplementation. The second examines the effect of Vitamin D supplementation in people with Rheumatoid Arthritis (RA). The reason for looking at an RA population is that CVD is the leading cause of early mortality in people with RA. In the first study 29 Post-Menopausal Women received either 100,000 IU of Vitamin D3 or a Placebo. Their FMD was measured at baseline and 2 weeks after supplementation. After 2 weeks there was a significant increase in FMD in the Vitamin D group (6.19 + 4.87 % to 10.69 + 5.18 %) as compared to the Placebo group (p=.03). In the second study, 11 older adults with RA were given 100,000 IU of Vitamin D or a Placebo. At baseline and one month later their FMD was examined as well as plasma concentrations of Vitamin D and tumor necrosis factor-alpha; (TNF-alpha;). They also filled out a Quality of Life Questionnaire and underwent a submaximal exercise test on the treadmill for estimation of maximum oxygen uptake (VO2max). There was no significant change in FMD in Vitamin D group as compared to the Placebo group (p=.721). Additionally, there was no significant improvement in either plasma Vitamin D or TNF-alpha; in the Vitamin D group. There was however a significant improvement in predicted VO2max from the submaximal exercise test in the group receiving Vitamin D (p=.003). The results of these studies suggest that a single 100,000 IU dose of Vitamin D can enhance FMD within two week in older adults, but that a similar dose may not be sufficient to increase FMD or plasma Vitamin D levels in older adults with RA. A more aggressive supplementation regimen may be required in this patient population.

Heart failure is a major worldwide health concern and is the leading cause of hospitalization among elderly Americans. Approximately 50% of those diagnosed with heart failure have heart failure with preserved ejection fraction (HFPEF). HFPEF presents a therapeutic dilemma because pharmacological strategies that are effective for the treatment of heart failure and reduced ejection fraction have failed to show benefit in HFPEF. Long term moderate intensity exercise programs have been shown to improve diastolic function in patients HFPEF. High intensity interval training (HIIT) has been shown to improve diastolic function in patients with heart failure and reduced ejection fraction. However, the effects of high intensity interval training in patients with HFPEF are unknown. Fourteen patients with HFPEF were randomized to either: (1) a novel program of high-intensity aerobic interval training (n = 8), or (2) a commonly prescribed program of moderate-intensity (MOD) aerobic exercise training (n = 6). Before and after four weeks of exercise training, patients underwent a treadmill graded exercise test for the determination of peak oxygen uptake (VO2peak), a brachial artery reactivity test for assessment of endothelium-dependent flow-mediated dilation (BAFMD), aortic pulse wave velocity assessment as an index of vascular stiffness and two-dimensional echocardiography for assessment of left ventricular diastolic and systolic function. I hypothesized that (1) high-intensity aerobic interval training would result in superior improvements in FMD, aortic pulse wave velocity, VO2peak, diastolic function and, (2) changes in these parameters would be correlated with changes in VO2peak. The principal findings of the study were that a one month long high intensity interval training program resulted in significant improvements in diastolic function as measured by two-dimensional echocardiography [pre diastolic dysfunction (DD) grade - 2.13 + 0.4 vs. post DD grade - 1.25 + 0.7, p = 0.03]. The left atrial volume index was reduced in the HIIT group compared to MOD ( - 4.4 + 6.2 ml/m2 vs. 5.8 + 10.7 ml/m2, p = 0.02). Early mitral flow (E) improved in the HIIT group (pre - 0.93 + 0.2 m/s vs. post - 0.78 + 0.3 m/s, p = 0.03). A significant inverse correlation was observed between change in BAFMD and change in diastolic dysfunction grade (r = - 0.585, p = 0.028) when all the data were pooled. HIIT appears to be a time-efficient and safe strategy for improving diastolic function in patients with heart failure and preserved ejection fraction. These data may have implications for cardiovascular risk reduction in this population.