Chronic Stress and Endothelial Dysfunction: The Multi-Ethnic Study of Atherosclerosis (MESA)

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).

Chronic stress: a crucial promoter of cell apoptosis in atherosclerosis

“…33,34 In the present study, the serum levels of hs-CRP, IL-6, and MCP-1 were significantly higher in the OPþHD group and were more obvious in the OPþHDþCS group. Moreover, intercellular adhesion molecule-1, the acute-phase reactant CRP, and the proinflammatory cytokine IL-6 were meaningfully higher in CS-treated apolipoprotein E knockout mice than in untreated animals as reported by Kershaw et al 35 and Chumaeva et al 36 Through general observation and examination of pathological sections, we found that CS had no impact on the intimal thickness but did result in a decrease in the medial thickness. However, previous studies have shown that CS can increase the total area of AS lesions.…”

Number of recent stressful life events and incident cardiovascular disease: Moderation by lifetime depressive disorder

“…Second, chronic exposure to stress may instigate atherogenic behaviors, including tobacco use and alcohol abuse, high fat and carbohydrate consumption, and physical inactivity (46, 47). Further supporting these candidate mechanisms, stressful life events have been cross-sectionally associated with increased endothelial dysfunction (48), and chronic work stress has been prospectively related to progression of subclinical atherosclerosis (49). However, in the current study, which is limited by two waves of data collection, we did not investigate these candidate mechanisms.…”

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

“…Physical activity was ascertained using the MESA Typical Week Physical Activity Survey, which was adapted from the Cross‐Cultural Activity Participation Survey 30, 41. At each visit, 3 resting BPs were measured by trained personnel using a Dinamap model Pro 100 automated oscillometric sphygmomanometer (Critikon) and the average of the last 2 measurements was used 30, 41, 42, 43. Hypertension was defined as a systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or use of antihypertensive medications 44.…”

“…30,41 At each visit, 3 resting BPs were measured by trained personnel using a Dinamap model Pro 100 automated oscillometric sphygmomanometer (Critikon) and the average of the last 2 measurements was used. 30,[41][42][43] Hypertension was defined as a systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or use of antihypertensive medications. 44 Measurements for lipid parameters were performed at a central laboratory using blood that had been collected after a 12-hour fast.…”