Abbi D. Lane-Cordova

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

BACKGROUND Endothelial 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). METHODS Data come from the baseline examination of Multi-Ethnic Study of Atherosclerosis participants. Chronic stress was assessed based on self-report of the presence and severity of ongoing problems in 5 domains. FMD was obtained using high-resolution ultrasound; biomarkers were assayed in different subsets of participants. RESULTS Higher chronic stress was associated with lower absolute FMD (mm FMD) in models adjusted for demographic and socioeconomic characteristics (0.169mm in high-stress participants vs. 0.178 and 0.179mm in medium and low-stress participants; P for trend = 0.04). This association remained unchanged with further adjustment for behavioral and biological CVD risk factors. Higher stress was related to higher ICAM-1 in models adjusted for sociodemographic characteristics and biological risk factors (P for trend = 0.005), but this association attenuated with adjustment for cigarette smoking (P for trend = 0.07). Chronic stress was not associated with E-selectin. CONCLUSIONS Our findings suggest chronic stress is related to endothelial dysfunction, possibly in part through other stress-associated CVD risk factors such as cigarette smoking.

Sex differences in autonomic function following maximal exercise

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.

The effect of acute maximal exercise on postexercise hemodynamics and central arterial stiffness in obese and normal‐weight individuals

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.

Differential Post-Exercise Blood Pressure Responses between Blacks and Caucasians

Post-exercise hypotension (PEH) is widely observed in Caucasians (CA) and is associated with histamine receptors 1- and 2- (H1R and H2R) mediated post-exercise vasodilation. However, it appears that blacks (BL) may not exhibit PEH following aerobic exercise. Hence, this study sought to determine the extent to which BL develop PEH, and the contribution of histamine receptors to PEH (or lack thereof) in this population. Forty-nine (22 BL, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either a combined H1R and H2R antagonist (fexofenadine and ranitidine) or a control placebo. Supine blood pressure (BP), cardiac output and peripheral vascular resistance measurements were obtained at baseline, as well as at 30 min, 60 min and 90 min after 45 min of treadmill exercise at 70% heart rate reserve. Exercise increased diastolic BP in young BL but not in CA. Post-exercise diastolic BP was also elevated in BL after exercise with histamine receptor blockade. Moreover, H1R and H2R blockade elicited differential responses in stroke volume between BL and CA at rest, and the difference remained following exercise. Our findings show differential BP responses following exercise in BL and CA, and a potential role of histamine receptors in mediating basal and post-exercise stroke volume in BL. The heightened BP and vascular responses to exercise stimulus is consistent with the greater CVD risk in BL.

Carotid β-stiffness index is associated with slower processing speed but not working memory or white matter integrity in healthy middle-aged/older adults

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 (P < 0.001) was greater and compliance (P < 0.001) was lower in MA/O (n = 32; 64.4 ± 4.3 yr) vs. young (n = 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, P < 0.001) and higher working memory cost (-15.4 ± 0.14 vs. -2.2 ± 0.05%, P < 0.001) vs. young adults. Global WMI was lower in MA/O adults (P < 0.001) and regionally in the frontal lobe (P = 0.020) and genu (P = 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, P = 0.001) and age group (B = -4.61 ± 1.7, P = 0.012, adjusted R2 = 0.4) predicted processing speed but not working memory cost or WMI. Among MA/O adults, higher β-stiffness (B = -0.60 ± 0.18, P = 0.002) and lower compliance (B = 0.93 ± 0.26, P = 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.NEW & NOTEWORTHY 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.

Effect of acute aerobic exercise and histamine receptor blockade on arterial stiffness in African Americans and Caucasians

African Americans (AA) exhibit exaggerated central blood pressure (BP) and arterial stiffness measured by pulse wave velocity (PWV) in response to an acute bout of maximal exercise compared with Caucasians (CA). However, whether potential racial differences exist in central BP, elastic, or muscular arterial distensibility after submaximal aerobic exercise remains unknown. Histamine receptor activation mediates sustained postexercise hyperemia in CA but the effect on arterial stiffness is unknown. This study sought to determine the effects of an acute bout of aerobic exercise on central BP and arterial stiffness and the role of histamine receptors, in AA and CA. Forty-nine (22 AA, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either histamine receptor antagonist or control placebo. Central blood BP and arterial stiffness measurements were obtained at baseline, and at 30, 60, and 90 min after 45 min of moderate treadmill exercise. AA exhibited greater central diastolic BP, elevated brachial PWV, and local carotid arterial stiffness after an acute bout of submaximal exercise compared with CA, which may contribute to their higher risk of cardiovascular disease. Unexpectedly, histamine receptor blockade did not affect central BP or PWV in AA or CA after exercise, but it may play a role in mediating local carotid arterial stiffness. Furthermore, histamine may mediate postexercise carotid arterial dilation in CA but not in AA. These observations provide evidence that young and healthy AA exhibit an exaggerated hemodynamic response to exercise and attenuated vasodilator response compared with CA.NEW & NOTEWORTHY African Americans are at greater risk for developing cardiovascular disease than Caucasians. We are the first to show that young and healthy African Americans exhibit greater central blood pressure, elevated brachial stiffness, and local carotid arterial stiffness following an acute bout of submaximal exercise compared with Caucasians, which may contribute to their higher risk of cardiovascular disease. Furthermore, African Americans exhibit attenuated vasodilator response compared with Caucasians.

Association Between Cardiovascular Health and Endothelial Function With Future Erectile Dysfunction: The Multi-Ethnic Study of Atherosclerosis

BACKGROUND The association of Cardiovascular Health (CVH; defined by the American Heart Association by assigning points for health-related behavioral and clinical factors) with endothelial and erectile dysfunction has not been reported, although endothelial and erectile dysfunction have been associated with components of CVH. METHODS Data were collected in 1,136 men in the Multi-Ethnic Study of Atherosclerosis at baseline and erectile dysfunction status (measured by survey or medication use) at exam 5. CVH was determined with 7 health metrics. Endothelial function was measured with brachial artery flow-mediated dilation (FMD). Poisson regression was used to determine associations between CVH and erectile dysfunction across categories of CVH (low, moderate, and high). RESULTS Age and proportion of Black or Latino participants decreased while proportion of Chinese-American participants increased with higher CVH category. FMD was higher in men without erectile dysfunction and higher in men with high vs. low CVH. Erectile dysfunction prevalence was lower with better CVH; 58% in men with low CVH, 41% with moderate CVH, and 33% with high CVH (P < 0.001). CVH was associated with erectile dysfunction; prevalence ratio = 0.75 (95% confidence interval (CI) = 0.66, 0.84) with moderate CVH and 0.68 (95% CI = 0.49, 0.94) with high CVH (vs. men with low CVH) and 0.93 (95% CI = 0.91, 0.96) for every 1-point higher CVH score in a fully adjusted model, including FMD, age, education, depression score, use of antidepressant or beta-blocker medications, chronic disease, heavy drinking, and race. CONCLUSION CVH is associated with future erectile dysfunction, even after adjustment for baseline FMD. Maintaining high CVH may improve quality of life for men.

Hemoglobin A1c and C-reactive protein are independently associated with blunted nocturnal blood pressure dipping in obesity-related prediabetes

Blunted nocturnal dipping in blood pressure (BP) is associated with increased cardiovascular disease (CVD) risk in middle-aged/older adults. The prevalence of blunted nocturnal BP dipping is higher in persons with obesity and diabetes, conditions that are also associated with elevated aortic stiffness and inflammation. Therefore, we hypothesized that elevated glycemia, inflammation and aortic stiffness would be inversely associated with the magnitude of nocturnal systolic BP dipping among middle-aged/older adults with obesity at high CVD risk. Twenty-four hour ambulatory BP monitoring, aortic stiffness (carotid–femoral pulse wave velocity, CF-PWV), hemoglobin A1c (HbA1c) and inflammation (C-reactive protein, CRP) were measured in 86 middle-aged/older adults with obesity and at least one other CVD risk factor (age 40–74 years; 34 male/52 female; body mass index=36.7±0.5 kg m−2; HbA1c=5.7±0.04%). In the entire cohort, CRP (β=0.40±0.20, P=0.04), but not HbA1c or CF-PWV was independently associated with systolic BP dipping percent (Model R2=0.07, P=0.12). In stratified (that is, presence or absence of prediabetes) multiple linear regression analysis, HbA1c (β=6.24±2.6, P=0.02) and CRP (β=0.57±0.2, P=0.01), but not CF-PWV (β=0.14± 2.6, P=0.74), were independently associated with systolic BP dipping percent (Model R2=0.32, P<0.01) in obese adults with prediabetes but were absent in obese adults without prediabetes (Model R2=0.01 P=0.95). However, nocturnal systolic BP dipping percent (P=0.65), CF-PWV (P=0.68) and CRP (P=0.59) were similar between participants with and without prediabetes. These data suggest that impaired long-term glycemic control and higher inflammation may contribute partly to blunted BP dipping in middle-aged/older adults with obesity-related prediabetes.

Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation

Background: Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. Method: Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C-reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. Results: Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 ± 0.8 to 8.3 ± 0.7 to 8.7 ± 0.7% in younger and from 5.8 ± 0.3 to 5.0 ± 0.4 to 4.7 ± 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 ± 0.1 to 1.4 ± 0.2 to 1.7 ± 0.3 mg/l), whereas the high-CRP group did not (from 4.8 ± 0.5 to 5.4 ± 0.5 to 5.4 ± 0.6 mg/l), P less than 0.001 for interaction. Conclusion: Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation.

Effects of ageing and physical activity on blood pressure and endothelial function during acute inflammation.

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.