Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure.

Central pulse pressure (PP) is the sum of forward and backward traveling pressure waves that have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding the importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45 ± 17 years, range 19-80 years, 61% women), from which the time integral of the forward (PfTI) and backward (PbTI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured ∼2 cm from the carotid bulb. Both PfTI (r = 0.31, P < 0.001) and PbTI (r = 0.40, P < 0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated = 156%, P < 0.001). The association between PbTI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B = 0.02, 95% confidence interval = 0.01, 2.77, P < 0.001). Both PfTI (r = -0.58, P < 0.001) and PbTI (r = -0.50, P < 0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated = 124%, P < 0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.NEW & NOTEWORTHY The present study contributes to the growing body of evidence highlighting the physiological and clinical insight provided by the pulsatile hemodynamic components of central artery pulse pressure. The notable findings of this study are: 1) The reflected (backward) pressure wave is associated with carotid intima-media thickness independent of traditional cardiovascular risk factors, including systolic blood pressure and aortic stiffness. 2) The incident (forward) pressure wave, and not the reflected pressure wave, is associated with greater central pulse pressure.

Sex-specific associations of reservoir-excess pressure parameters with age and subclinical vascular remodeling.

OBJECTIVE: Central artery reservoir pressure and excess pressure (XSP) are associated with cardiovascular disease (CVD) events and mortality. However, sex differences in the trajectory of central reservoir pressure and XSP with advancing age and their relations with vascular markers of subclinical CVD risk are incompletely understood. Therefore, we tested the hypothesis that central reservoir pressure and XSP would be positively associated with advancing age and vascular markers of subclinical CVD risk in men and women. METHOD: Healthy adults ( n  = 398; aged 18-80 years, 60% female individuals) had central (carotid) artery pressure waveforms acquired by applanation tonometry. Reservoir pressure and XSP peaks and integrals were derived retrospectively from carotid pressure waveforms using custom written software. Carotid artery intimal-medial thickness (IMT) was measured by ultrasonography, and aortic stiffness was determined from carotid-femoral pulse wave velocity (cfPWV). RESULTS: Reservoir pressure peak, reservoir pressure integral and XSP integral were higher with age in both men and women ( P  < 0.05), whereas XSP peak was lower with age in men ( P  < 0.05). In women, both reservoir pressure peak ( ß â€Š= 0.231, P  < 0.01) and reservoir pressure integral ( ß â€Š= 0.254, P  < 0.01) were associated with carotid artery IMT, and reservoir pressure peak was associated with cfPWV ( ß â€Š= 0.120, P  = 0.02) after adjusting for CVD risk factors. CONCLUSION: Central artery reservoir pressure and XSP were higher with advancing age in men and women, and reservoir pressure peak was associated with both carotid artery wall thickness and aortic stiffness in women but not men. Central reservoir pressure peak may provide some insight into sex differences in vascular remodeling and subclinical CVD risk with advancing age in healthy adults.

Concomitantly higher resting arterial blood pressure and transduction of sympathetic neural activity in human obesity without hypertension.

OBJECTIVE: Central (abdominal) obesity is associated with elevated adrenergic activity and arterial blood pressure (BP). Therefore, we tested the hypothesis that transduction of spontaneous muscle sympathetic nerve activity (MSNA) to BP, that is, sympathetic transduction, is augmented in abdominal obesity (increased waist circumference) and positively related to prevailing BP. METHODS: Young/middle-aged obese (32 ±â€Š7 years; BMI: 36 ±â€Š5 kg/m2, n = 14) and nonobese (29 ±â€Š10 years; BMI: 23 ±â€Š4 kg/m2, n = 14) without hypertension (24-h ambulatory average BP < 130/80 mmHg) were included. MSNA (microneurography) and beat-to-beat BP (finger cuff) were measured continuously and the increase in mean arterial pressure (MAP) during 15 cardiac cycles following MSNA bursts of different patterns (single, multiples) and amplitude (quartiles) was signal-averaged over a 10 min baseline period. RESULTS: MSNA burst frequency was not significantly higher in obese vs. nonobese (21 ±â€Š3 vs. 17 ±â€Š3 bursts/min, P = 0.34). However, resting supine BP was significantly higher in obese compared with nonobese (systolic: 127 ±â€Š3 vs. 114 ±â€Š3; diastolic: 76 ±â€Š2 vs. 64 ±â€Š1 mmHg, both P < 0.01). Importantly, obese showed greater increases in MAP following multiple MSNA bursts (P = 0.02) and MSNA bursts of higher amplitude (P = 0.02), but not single MSNA bursts (P = 0.24), compared with nonobese when adjusting for MSNA burst frequency. The increase in MAP following higher amplitude bursts among all participants was associated with higher resting supine systolic (R = 0.48; P = 0.01) and diastolic (R = 0.48; P = 0.01) BP when controlling for MSNA burst frequency, but not when also controlling for waist circumference (P > 0.05). In contrast, sympathetic transduction was not correlated with 24-h ambulatory average BP. CONCLUSION: Sympathetic transduction to BP is augmented in abdominal obesity and positively related to higher resting supine BP but not 24-h ambulatory average BP.

Cognitive performance is lower among individuals with overlap syndrome than in individuals with COPD or obstructive sleep apnea alone: association with carotid artery stiffness.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack years, and postbronchodilator FEV1/FVC. We also examined the association between CCA stiffness and cognitive performance among each group separately. Individuals with overlap syndrome (n = 12) had greater CCA ß-stiffness index (P = 0.015) and lower executive function-processing speed (P = 0.019) than individuals with COPD alone (n = 47), OSA alone (n = 9), and former smoker controls (n = 21), differences that remained significant after adjusting for age, BMI, sex, pack years, and FEV1/FVC. Higher CCA ß-stiffness index was associated with lower executive function-processing speed in individuals with overlap syndrome (r = -0.58, P = 0.047). These data suggest that CCA stiffness is greater and cognitive performance is lower among individuals with overlap syndrome compared with individuals with COPD or OSA alone and that CCA stiffening may be an underlying mechanism contributing to the lower cognitive performance observed in patients with overlap syndrome.NEW & NOTEWORTHY Previous studies have demonstrated greater carotid artery stiffness and lower cognitive function among individuals with COPD alone and OSA alone. However, the present study is the first to demonstrate that individuals that have both COPD and OSA (i.e., overlap syndrome) have greater carotid artery stiffness and lower executive function-processing speed than individuals with either disorder alone. Furthermore, among individuals with overlap syndrome greater carotid artery stiffness is associated with lower executive function-processing speed.

Cigarette Smoking and Longitudinal Associations With Blood Pressure: The CARDIA Study.

Background The associations of chronic cigarette smoking with blood pressure (BP) remain mixed. It is unclear whether a lack of examination of racial differences contributed to the mixed findings in previous studies. Black smokers metabolize nicotine at a slower rate than White smokers and racial discrimination contributes to nicotine dependence and higher BP among Black smokers. Methods and Results We studied the association between cigarette smoking and longitudinal (30-year) changes in systolic BP, diastolic BP, and pulse pressure (PP) in 4786 Black and White individuals from the CARDIA (Coronary Artery Risk Development in Young Adults) study using repeated-measures regression models. Neither systolic BP, nor diastolic BP differed between Black consistent smokers compared with Black never smokers, although Black consistent smokers had higher PP than Black never smokers (ß=1.01 mm Hg, P=0.028). White consistent smokers had similar systolic BP, but lower diastolic BP (ß=-2.27 mm Hg, P<0.001) and higher PP (ß=1.59 mm Hg, P<0.001) compared with White never smokers. There were no differences in systolic BP, diastolic BP, or PP between Black or White long-term former smokers compared with never smokers (all P>0.05). Conclusions Although the associations of cigarette smoking with alterations in BP are small, the greater PP observed in consistent smokers may contribute in part to the higher cardiovascular disease risk observed in this group because PP is a strong predictor of cardiovascular disease risk after middle age.

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort: Relation With Aortic Stiffness.

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P=0.001; second: 5.1±1.8 versus 3.8±1.1, P=0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P=0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27-2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P=0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P=0.002) and was associated with BPV after adjustment for mean blood pressure (r=0.26; P=0.005). First trimester baroreflex sensitivity did not differ between groups (P=0.23) and was not related to BPV (P=0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.

Sex and age differences in the association between sympathetic outflow and central elastic artery wall thickness in humans.

Aging is characterized by increased wall thickness of the central elastic arteries (i.e., aorta and carotid arteries), although the mechanisms involved are unclear. Evidence suggests that age-related increases in muscle sympathetic nerve activity (MSNA) may be a contributing factor. However, studies in humans have been lacking. Therefore, we tested the hypothesis that age-related increases in MSNA would be independently associated with carotid artery intima-media thickness (IMT) but not in young women given the reduced influence of MSNA on the vasculature in this group. In 93 young and middle-age/older (MA/O) adults (19-73 yr, 41 women), we performed assessments of MSNA (microneurography) and common carotid IMT and lumen diameter (ultrasonography). Multiple regression that included MSNA and other cardiovascular disease risk factors indicated that MSNA (P = 0.002) and 24-h systolic blood pressure (BP) (P = 0.024) were independent determinants of carotid IMT-to-lumen ratio (model R2 = 0.38, P < 0.001). However, when examining only young women (<45 yr), no correlation was observed between MSNA and carotid IMT-to-lumen ratio (R = -0.01, P = 0.963). MSNA was significantly correlated with IMT-to-lumen ratio while controlling for 24-h systolic BP among young men (R = 0.49, P < 0.001) and MA/O women (R = 0.59, P = 0.022). However, among MA/O men, controlling for 24-h systolic BP attenuated the association between MSNA and carotid IMT-to-lumen ratio (R = 0.50, P = 0.115). Significant age differences in IMT-to-lumen ratio between young and MA/O men (P = 0.047) and young and MA/O women (P = 0.023) were removed when adjusting for MSNA (men: P = 0.970; women: P = 0.152). These findings demonstrate an association between higher sympathetic outflow and carotid artery wall thickness with a particular exception to young women.NEW & NOTEWORTHY Increased wall thickness of the large elastic arteries serves as a graded marker for cardiovascular disease risk and progression of atherosclerosis. Findings from the present study establish an independent association between higher sympathetic outflow and carotid artery wall thickness in adults with an exception to young women and extend findings from animal models that demonstrate hypertrophy of vascular smooth muscle following chronic sympathetic-adrenergic stimulation.

Elevated Muscle Sympathetic Nerve Activity Contributes to Central Artery Stiffness in Young and Middle-Age/Older Adults.

Muscle sympathetic nerve activity (MSNA) influences the mechanical properties (ie, vascular smooth muscle tone and stiffness) of peripheral arteries, but it remains controversial whether MSNA contributes to stiffness of central arteries, such as the aorta and carotids. We examined whether elevated MSNA (age-related) would be independently associated with greater stiffness of central (carotid-femoral pulse wave velocity [PWV]) and peripheral (carotid-brachial PWV) arteries, in addition to lower carotid compliance coefficient, in healthy men and women (n=88, age: 19-73 years, 52% men). We also examined whether acute elevations in MSNA without increases in mean arterial pressure using graded levels of lower body negative pressure would augment central and peripheral artery stiffness in young (n=15, 60% men) and middle-age/older (MA/O, n=14, 43% men) adults. Resting MSNA burst frequency (bursts·min-1) was significantly correlated with carotid-femoral PWV ( R=0.44, P<0.001), carotid-brachial PWV ( R=0.32, P=0.004), and carotid compliance coefficient ( R=0.28, P=0.01) after controlling for sex, mean arterial pressure, heart rate, and waist-to-hip ratio (central obesity), but these correlations were abolished after further controlling for age (all P>0.05). In young and MA/O adults, MSNA was elevated during lower body negative pressure ( P<0.001) and produced significant increases in carotid-femoral PWV (young: Δ+1.3±0.3 versus MA/O: Δ+1.0±0.3 m·s-1, P=0.53) and carotid-brachial PWV (young: Δ+0.7±0.3 versus MA/O: Δ+0.7±0.5 m·s-1, P=0.92), whereas carotid compliance coefficient during lower body negative pressure was significantly reduced in young but not MA/O (young: Δ-0.04±0.01 versus MA/O: Δ0.001±0.008 mm2·mm Hg-1, P<0.01). Collectively, these data demonstrate the influence of MSNA on central artery stiffness and its potential contribution to age-related increases in stiffness of both peripheral and central arteries.

CT-measured lung air-trapping is associated with higher carotid artery stiffness in individuals with chronic obstructive pulmonary disease.

Early stages of chronic obstructive pulmonary disease (COPD) are characterized by the loss and narrowing of terminal bronchioles in the lung, resulting in "air-trapping," often occurring before overt emphysema manifests. Individuals with an airway-predominant phenotype of COPD display extensive lung air-trapping and are at greater cardiovascular disease (CVD) risk than COPD patients with an emphysema-predominant phenotype. We hypothesized that the degree of computed tomography (CT)-quantified lung air-trapping would be associated with greater aortic and carotid artery stiffness and lower endothelial function, known biomarkers of CVD risk. Lung air-trapping was associated with greater aortic stiffness (carotid femoral pulse wave velocity, CFPWV) (r = 0.60, P = 0.007) and carotid ß-stiffness (r = 0.75, P = 0.0001) among adults with (n = 10) and without (n = 9) a clinical diagnosis of COPD and remained significant after adjusting for blood pressure (BP) and smoking history (pack-years) (carotid ß-stiffness: r = 0.68, P < 0.01; CFPWV r = 0.53, P = 0.03). The association between lung air-trapping and carotid ß-stiffness remained significant after additionally adjusting for age and forced expiratory volume 1(FEV1) (r = 0.64, P = 0.01). In the COPD group only (n = 10), lung air-trapping remained associated with carotid ß-stiffness (r = 0.82, P = 0.05) after adjustment for age, pack-years, and FEV1. In contrast, no association was observed between CFPWV and lung air-trapping after adjustment for BP, pack-years, age, and FEV1 (r = 0.12, P = 0.83). Lung air-trapping was not associated with endothelial function (brachial artery flow-mediated dilation) in the entire cohort (P = 0.80) or in patients with COPD only (P = 0.71). These data suggest that carotid artery stiffness may be a mechanism explaining the link between airway-predominant phenotypes of COPD and high CVD risk.NEW & NOTEWORTHY Previous cross-sectional studies have demonstrated greater large elastic artery stiffness and lower endothelium-dependent dilation in chronic obstructive pulmonary disease (COPD) patients compared with controls. Furthermore, COPD patients with emphysema have greater aortic stiffness than non-COPD controls, and the degree of stiffness is associated with emphysema severity. The present study is the first to demonstrate that even before overt emphysema manifests, lung air-trapping is associated with carotid artery stiffness in COPD patients independent of blood pressure, age, or smoking history.

Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety.

Relative burst amplitude of muscle sympathetic nerve activity (MSNA) is an indicator of augmented sympathetic outflow and contributes to greater vasoconstrictor responses. Evidence suggests anxiety-induced augmentation of relative MSNA burst amplitude in patients with panic disorder; thus we hypothesized that acute stress would result in augmented relative MSNA burst amplitude and vasoconstriction in individuals with chronic anxiety. Eighteen participants with chronic anxiety (ANX; 8 men, 10 women, 32 ± 2 yr) and 18 healthy control subjects with low or no anxiety (CON; 8 men, 10 women, 39 ± 3 yr) were studied. Baseline MSNA and 24-h blood pressure were similar between ANX and CON ( P > 0.05); however, nocturnal systolic blood pressure % dipping was blunted among ANX ( P = 0.02). Relative MSNA burst amplitude was significantly greater among ANX compared with CON immediately preceding (anticipation) and during physiological stress [2-min cold pressor test; ANX: 73 ± 5 vs. CON: 59 ± 3% arbitrary units (AU), P = 0.03] and mental stress (4-min mental arithmetic; ANX: 65 ± 3 vs. CON: 54 ± 3% AU, P = 0.02). Increases in MSNA burst frequency, incidence, and total activity in response to stress were not augmented among ANX compared with CON ( P > 0.05), and reduction in brachial artery conductance during cold stress was similar between ANX and CON ( P = 0.92). Relative MSNA burst amplitude during mental stress was strongly correlated with state ( P < 0.01) and trait ( P = 0.01) anxiety (State-Trait Anxiety Inventory), independent of age, sex, and body mass index. Thus in response to acute stress, both mental and physiological, individuals with chronic anxiety demonstrate selective augmentation in relative MSNA burst amplitude, indicating enhanced sympathetic drive in a population with higher risk for cardiovascular disease. NEW & NOTEWORTHY Relative burst amplitude of muscle sympathetic nerve activity in response to acute mental and physiological stress is selectively augmented in individuals with chronic anxiety, which is a prevalent condition that is associated with the development of cardiovascular disease. Augmented sympathetic burst amplitude occurs with chronic anxiety in the absence of common comorbidities. These findings provide important insight into the relation between anxiety, acute stress and sympathetic activation.