No abstract

Research suggests stress is a risk factor for cardiovascular disease (CVD), 1-4 but the underlying mechanisms remain unclear. Mental stress activates the sympathetic nervous system, 5 causing a constellation of adverse cardiovascular effects, including increased blood pressure, heart rate, and endothelial dysfunction. 6 One potential pathway through which chronic exposure to psychosocial stressors are hypothesized to influence CVD risk is through injury to the endothelial lining of blood vessels due to sustained and repeated activation of the sympathetic nervous system. 7 Endothelial dysfunction plays a critical role in the initiation and progression of atherosclerosis, 8 and thus, may be a major pathway linking chronic stress and CVD.Studies have shown that acute exposure to a mental stressor is significantly associated with prolonged endothelial dysfunction, 6,9 but few studies have examined the impact of chronic stress and these studies have been in ethnically homogeneous populations. A national study of non-Hispanic Whites found that chronic exposure to discrimination predicted higher levels of circulating endothelial-leukocyte adhesion molecule-1 (E-selectin), an indicator of endothelial dysfunction, in men but not women. 10 Two studies of caregivers (>80% non-Hispanic White) found that global stress and caregiver stress were each associated with lower brachial artery flow-mediated dilation (FMD). 11,12 In this study, we examined associations of chronic stress with 3 markers of endothelial dysfunction in a multiethnic population of middle-and older-age adults. Brachial artery FMD is a noninvasive, commonly used method to assess endothelial function of the peripheral conduit artery. With this method, reduced artery dilation is suggestive of poorer endothelial function. We also included 2 serological biomarkers of endothelial dysfunction: intercellular adhesion molecule-1 (ICAM-1) and E-selectin. These cellular adhesion molecules are expressed on the surfaces of endothelial cells as part of the inflammatory response to endothelial damage. We hypothesized that higher chronic stress would be associated with lower FMD, higher ICAM-1, and higher E-selectin levels. Given previous heterogeneous findings by gender, 10 and the dearth of studies in multiethnic populations, we also examined whether associations varied by race/ ethnicity or gender. Chronic Stress and Endothelial BACKGROUNDEndothelial dysfunction may represent an important link between chronic stress and cardiovascular disease (CVD) risk. However, few studies have examined the impact of chronic stress on endothelial dysfunction. The purpose of this study was to examine whether chronic stress was associated with flow-mediated dilation (FMD) and 2 biomarkers of endothelial dysfunction (intercellular adhesion molecule-1 (ICAM-1) and E-selectin) in a multiethnic sample of adults (ages 45-84 years).

Central arterial stiffness is associated with incident hypertension and negative cardiovascular outcomes. Obese individuals have higher central blood pressure (BP) and central arterial stiffness than their normal‐weight counterparts, but it is unclear whether obesity also affects hemodynamics and central arterial stiffness after maximal exercise. We evaluated central hemodynamics and arterial stiffness during recovery from acute maximal aerobic exercise in obese and normal‐weight individuals. Forty‐six normal‐weight and twenty‐one obese individuals underwent measurements of central BP and central arterial stiffness at rest and 15 and 30 min following acute maximal exercise. Central BP and normalized augmentation index (AIx@75) were derived from radial artery applanation tonometry, and central arterial stiffness was obtained via carotid‐femoral pulse wave velocity (cPWV) and corrected for central mean arterial pressure (cPWV/cMAP). Central arterial stiffness increased in obese individuals but decreased in normal‐weight individuals following acute maximal exercise, after adjusting for fitness. Obese individuals also exhibited an overall higher central BP (P < 0.05), with no exercise effect. The increase in heart rate was greater in obese versus normal‐weight individuals following exercise (P < 0.05), but there was no group differences or exercise effect for AIx@75. In conclusion, obese (but not normal‐weight) individuals increased central arterial stiffness following acute maximal exercise. An assessment of arterial stiffness response to acute exercise may serve a useful detection tool for subclinical vascular dysfunction.

Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24 h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P < 0.05). The YA (low fit, from 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit, from 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (from 7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24 h (P < 0.05). Low-fit OA did not reduce FMD at 24 h (from 5.5 ± 0.4 to 5.2 ± 0.5%, P > 0.05). The reduction in FMD in YA was similar between fitness groups (P > 0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. The augmentation index and carotid elastic modulus did not change during acute inflammation. In conclusion, in OA, higher fitness is associated with a greater decrease in endothelial function during acute inflammation, and this response is similar to that of young adults. This suggests that moderately fit OA may maintain vascular reactivity in response to stress, indicating preserved vascular function in moderately fit versus low-fit OA.

Arterial stiffness is related to the risk of cardiovascular disease (CVD) and increases with aging. Functional impairment of the arterial wall can occur before structural changes and can be detectable before CVD symptoms. The elastic properties of the carotid arterial wall during the cardiac cycle can be evaluated by standard 2-dimensional (2D) ultrasound longitudinal or circumferential imaging of vascular deformation (strain) using speckle tracking. The purpose of this study was to compare standard 2D ultrasound circumferential and longitudinal images of vascular tissue motion and strain using speckle tracking in young and older individuals. Participants underwent recording of 2D ultrasound circumferential and longitudinal images of the common carotid artery. Circumferential carotid strain (CS) and CS rate were obtained and analyzed via speckle tracking software. Following the strain analysis, the circumferential strain β-stiffness (C-β) was calculated. Conventional longitudinal β-stiffness (L-β) was calculated and non-invasive blood pressure measurements were obtained from carotid artery pressure measurements in a resting supine position using applanation tonometry. C-β was significantly higher than L-β, and the association with age was greater (r = .824 vs. r = .547). CS and CS rate were significantly higher in the young compared to the older group. L-β does not explain as much of the age-dependent differences in the carotid artery compared with C-β. This is possibly due to the inclusion of whole arterial wall motion and deformation observed in the CS image. The ability of C-β to accurately predict the future risk of CVD independent of age still needs further investigation.

Aging is associated with increased carotid artery stiffness, a predictor of incident stroke, and reduced cognitive performance and brain white matter integrity (WMI) in humans. Therefore, we hypothesized that higher carotid stiffness/lower compliance would be independently associated with slower processing speed, higher working memory cost, and lower WMI in healthy middle-aged/older (MA/O) adults. Carotid β-stiffness ( < 0.001) was greater and compliance ( < 0.001) was lower in MA/O ( = 32; 64.4 ± 4.3 yr) vs. young ( = 19; 23.8 ± 2.9 yr) adults. MA/O adults demonstrated slower processing speed (27.4 ± 4.6 vs. 35.4 ± 5.0 U/60 s, < 0.001) and higher working memory cost (-15.4 ± 0.14 vs. -2.2 ± 0.05%, < 0.001) vs. young adults. Global WMI was lower in MA/O adults ( < 0.001) and regionally in the frontal lobe ( = 0.020) and genu ( = 0.009). In the entire cohort, multiple regression analysis that included education, sex, and body mass index, carotid β-stiffness index (B = -0.53 ± 0.15 U, = 0.001) and age group (B = -4.61 ± 1.7, = 0.012, adjusted = 0.4) predicted processing speed but not working memory cost or WMI. Among MA/O adults, higher β-stiffness (B = -0.60 ± 0.18, = 0.002) and lower compliance (B = 0.93 ± 0.26, = 0.002) were associated with slower processing speed but not working memory cost or WMI. These data suggest that greater carotid artery stiffness is independently and selectively associated with slower processing speed but not working memory among MA/O adults. Carotid artery stiffening may modulate reductions in processing speed earlier than working memory with healthy aging in humans. Previously, studies investigating the relation between large elastic artery stiffness, cognition, and brain structure have focused mainly on aortic stiffness in aged individuals with cardiovascular disease risk factors and other comorbidities. This study adds to the field by demonstrating that the age-related increases in carotid artery stiffness, but not aortic stiffness, is independently and selectively associated with slower processing speed but not working memory among middle-aged/older adults with low cardiovascular disease risk factor burden.

What is the central question of this study? Do older and younger adults have similar vascular endothelial and blood pressure responses to acute inflammation? Does physical activity affect these responses? What is the main finding and its importance? Older adults reduce blood pressure whereas younger adults reduce endothelial function during acute inflammation. Physical activity does not provide protection against these inflammation-induced changes. This is important because older adults regularly experience acute increases in systemic inflammation that may predispose older adults to cardiovascular events through dysregulation of blood pressure. Ageing is characterized by chronic, low-grade inflammation that is related to endothelial dysfunction and arterial stiffness. Physical activity can protect older adults (OAs) from cardiovascular dysfunction and increased inflammation. Acute inflammation causes transient endothelial dysfunction and arterial stiffening in younger adults (YAs), but may not have the same effect in OAs. We hypothesized that acute inflammation would increase blood pressure (BP) and endothelial impairment to a greater extent in OAs versus YAs, but that physical activity would be protective. We induced inflammation with an influenza vaccine in 22 OAs (55-75 years old) and 31 YAs (18-35 years old) and measured brachial flow-mediated dilatation (FMD), BP and serum inflammatory markers before vaccination and at 24 and 48 h afterwards. Physical activity data were collected using accelerometry. During inflammation, only OAs reduced systolic BP (from 120 ± 3 to 115 ± 2 to 115 ± 3 mmHg, P < 0.05), but only YAs reduced FMD (from 11.3 ± 0.7 to 8.5 ± 0.6 to 8.9 ± 0.6% in YAs and from 6.7 ± 0.6 to 5.3 ± 0.7 to 6.0 ± 0.6% in OAs, P < 0.05 for time and interaction effects). The entire cohort increased C-reactive protein (P < 0.05), but only YAs increased interleukin-6 (P < 0.05 for time × age group interaction). Physical activity was related to the percentage change in inflammation in OAs (r = -0.50, P < 0.05) but not to the change in arterial function in either group (P > 0.05 for all). We conclude that acute inflammation reduced FMD only in YAs and reduced BP only in OAs. Physical activity did not affect arterial function during acute inflammation. Clinicians should be aware that all OAs are vulnerable to inflammation-mediated reductions in BP and cardiovascular complications.

BackgroundHeart rate variability (HRV), blood pressure variability, (BPV) and heart rate recovery (HRR) are measures that provide insight regarding autonomic function. Maximal exercise can affect autonomic function, and it is unknown if there are sex differences in autonomic recovery following exercise. Therefore, the purpose of this study was to determine sex differences in several measures of autonomic function and the response following maximal exercise.MethodsSeventy-one (31 males and 40 females) healthy, nonsmoking, sedentary normotensive subjects between the ages of 18 and 35 underwent measurements of HRV and BPV at rest and following a maximal exercise bout. HRR was measured at minute one and two following maximal exercise.ResultsMales have significantly greater HRR following maximal exercise at both minute one and two; however, the significance between sexes was eliminated when controlling for VO2 peak. Males had significantly higher resting BPV-low-frequency (LF) values compared to females and did not significantly change following exercise, whereas females had significantly increased BPV-LF values following acute maximal exercise. Although males and females exhibited a significant decrease in both HRV-LF and HRV-high frequency (HF) with exercise, females had significantly higher HRV-HF values following exercise. Males had a significantly higher HRV-LF/HF ratio at rest; however, both males and females significantly increased their HRV-LF/HF ratio following exercise.ConclusionsPre-menopausal females exhibit a cardioprotective autonomic profile compared to age-matched males due to lower resting sympathetic activity and faster vagal reactivation following maximal exercise. Acute maximal exercise is a sufficient autonomic stressor to demonstrate sex differences in the critical post-exercise recovery period.