Objective
To determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity.
Methods
Eighty-seven individuals who were 60 years of age or older (age = 69 ± 7 yrs; mean ± SD) were grouped into normal weight (BMI < n =" 30)," n =" 28)," n =" 29)" p =" 0.038)" p =" 0.001)" p =" 0.006," r =" -0.44," r =" -0.37," r =" -0.36," p =" 0.001," r =" -0.32," p =" 0.002)." bmi =" weight" r =" 0.86"> 0.05) to calf blood flow obtained at rest. BMI was inversely related to the post-occlusive reactive hyperemic calf blood flow (r = -0.25, p = 0.022), and to the absolute change (r = -0.44, p < r =" -0.37," r =" -0.21," p =" 0.047)," r =" -0.36," p =" 0.001)" r =" -0.32," p =" 0.002)">
Figure 1. The relationship between body mass index and the percentage change in calf blood flow from rest to post-occlusive reactive hyperemia (r = -0.37, p <>
Figure 2. The relationship between waist circumference and percentage change in calf blood flow from rest to post-occlusive reactive hyperemia (r = -0.32, p = 0.002).
One subject had a percentage change in calf blood flow that exceeded 900%. We used two different approaches to assess whether this data point had an influence on the relationships shown in Figures 1 and 2. In the first approach, we used non-parametric procedures by calculating the Spearman Rank correlation coefficients. The percentage change in calf blood flow remained significantly related to BMI (r = -0.38, p < r =" -0.33," p =" 0.002)," r =" -0.23," p =" 0.036)," r =" -0.36," p =" 0.001)" r =" -0.28," p =" 0.014)" r =" -0.33," p =" 0.002)" r =" -0.26," p =" 0.019)">
Discussion
This investigation compared the reactive hyperemic response to three minutes of arterial occlusion in older adults having a wide range in BMI, and determined if calf blood flow differences among normal weight, overweight, and obese older adults persisted after adjusting for confounders, such as age and hypertension. The primary findings were: (1) the obese group had a blunted change in post-occlusive reactive hyperemic blood flow, indicative of impaired vascular reactivity, than the normal weight group, and (2) the difference in vascular reactivity between the obese and normal weight groups remained significant after controlling for age, hypertension and calf skinfold thickness.
The observation that obesity impairs vascular reactivity supports previous studies in young and healthy adults [8,16,21], and extends this finding to obese older adults who are free of overt cardiovascular disease. This suggests that obesity-mediated vascular dysfunction in older adults is due to impairment in endothelial function [8,16]. Our results are further supported by a report that found an inverse correlation between obesity and endothelial-independent vasodilation [22] in a small sample of older adults with diabetes. Collectively, these findings suggest that obesity has a detrimental impact on endothelial function in older adults with and without diabetes.
Besides the negative consequences of obesity on vascular function in older populations, obesity-mediated alterations in endothelial function are evident even in young adults. A lower response in endothelial-dependent vasodilation and forearm blood flow after an infusion of acetylcholine (ACh) is observed in obese, young adults compared to overweight and normal weight young adults [8]. Accumulation of abdominal fat is the primary factor for endothelial dysfunction [21]. Interestingly, endothelial function may be positively altered following a weight loss program. A prospective investigation found ACh-stimulated forearm blood flow improved following a reduction in body size and waist circumference [16]. In speculation, a program designed to decrease adiposity may improve endothelial function in older, obese adults.
The increased prevalence of chronic vascular complications consistently shown in the aging population [23,24] further complicates the association between obesity and endothelial function. The development of endothelial dysfunction and, ultimately, atherosclerosis has specifically been linked to diabetes [25], hypertension [26], and hypercholesterolemia [27], all of which increase in prevalence with advancing age [28]. Additionally, lifestyle behaviors such as physical inactivity and smoking, impair endothelial function and initiate atherosclerotic processes [23,24,29-31]. The lack of control of these co-morbid conditions leaves previous results inconclusive regarding the independent role of obesity in the pathogenesis of endothelial dysfunction. The current investigation attempted to minimize these confounding factors by excluding subjects with cardiovascular disease, diabetes, and a history of smoking during the previous year. Furthermore, vascular reactivity measurements were adjusted for group differences in age, prevalence of hypertension and calf skinfold thickness. These approaches improve the ability to determine the influence of obesity on vascular reactivity.
Finally, subcutaneous body fat, as assessed by the sum of skinfolds, did not show any relationship to blood flow or to vascular reactivity in this population. In contrast, the central distribution of adipose tissue, as assessed by waist circumference, was inversely related to vascular reactivity of these older adults. Taken collectively, these results suggest that visceral adiposity may have a more detrimental influence on vascular reactivity (i.e., endothelial dysfunction) than subcutaneous fat. Our findings are supported by a previous observation that impairment in flow-mediated, endothelium-dependent vasodilation of the brachial artery occurs with visceral obesity, rather than with subcutaneous obesity [32].
One limitation to this study is the cross-sectional design which does not establish a causal link between obesity and impaired vascular reactivity. Intervention and longitudinal studies that track changes in fat mass and vascular reactivity are necessary to better determine their association. Although we normalized the blood flow measures according to subcutaneous fat of the calf, as estimated by the calf skinfold, we did not measure intra-muscular fat. Therefore, it is possible that the difference in blood flow among the groups is partially attributed to differences in intra-muscular fat of the calf. Additionally, the measurement of vascular reactivity by the method of reactive hyperemia assesses the vasodilatory function of both the endothelium and vascular smooth muscle, and therefore is only an indirect assessment of endothelial function. The lack of physical activity measurement is another limitation to this study. Physical activity status is associated with blood flow [24] and endothelial-dependent vasodilatory function [29] and, thus, should be considered in future studies examining the influence of obesity and abdominal fat on vascular reactivity.
Although our investigation minimized confounding factors by excluding for cardiovascular disease and controlling for many primary risk factors of atherosclerosis, we did not adjust for the possible influence of secondary risk factors, such as C-reactive protein or other inflammatory markers [33,34]. Furthermore, a medical history was used to exclude participants with diagnosed cardiovascular disease and diabetes, but those with undiagnosed conditions may not have been identified. That said, the possibility exists that our self-report method of revealing existing disease does allow for an underestimated prevalence of diabetes. Lastly, our assessment of adiposity was limited to BMI and anthropometric measures rather than more precise measurements of body fat and displacement of adiposity.
In conclusion, obesity and abdominal adiposity impair vascular reactivity in older men and women, and these deleterious effects on vascular reactivity are independent of conventional risk factors. Consequently, impaired vascular reactivity may increase the risk for subsequent cardiovascular complications in older, obese adults.
Xanya Sofra Weiss
Xanya Sofra Weiss
