Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population.

BACKGROUND: Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality. METHODS AND RESULTS: We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R2=0.27 and R2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality. CONCLUSIONS: Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.

The effect of cardiorespiratory fitness and habitual physical activity on cardiovascular responses to 2 h of uninterrupted sitting.

Prolonged uninterrupted sitting of >3 h has been shown to acutely cause central and peripheral cardiovascular dysfunction. However, individuals rarely sit uninterrupted for >2 h, and the cardiovascular response to this time is currently unknown. In addition, while increased cardiorespiratory fitness (CRF) and habitual physical activity (HPA) are independently associated with improvements in central and peripheral cardiovascular function, it remains unclear whether they influence the response to uninterrupted sitting. This study sought to 1) determine whether 2 h of uninterrupted sitting acutely impairs carotid-femoral pulse wave velocity (cfPWV), femoral ankle PWV (faPWV), and central and peripheral blood pressure and 2) investigate the associations between CRF and HPA versus PWV changes during uninterrupted sitting. Following 2 h of uninterrupted sitting, faPWV significantly increased [mean difference (MD) = 0.26 m·s-1, standard error (SE) = 0.10, P = 0.013] as did diastolic blood pressure (MD = 2.83 mmHg, SE = 1.08, P = 0.014), however, cfPWV did not significantly change. Although our study shows 2 h of uninterrupted sitting significantly impairs faPWV, neither CRF (r = 0.105, P = 0.595) nor HPA (r = -0.228, P = 0.253) was associated with the increases.NEW & NOTEWORTHY We demonstrate that neither cardiorespiratory fitness nor habitual physical activity influence central and peripheral cardiovascular responses to a 2-h bout of uninterrupted sitting in healthy young adults.

Serum Phenylacetylglutamine among Potential Risk Factors for Arterial Stiffness Measuring by Carotid-Femoral Pulse Wave Velocity in Patients with Kidney Transplantation.

Phenylacetylglutamine (PAG), a gut microbiota metabolite, is associated with cardiovascular diseases. Arterial stiffness (AS), which is a marker of aging-associated vascular diseases, is an independent risk factor for cardiovascular morbidity and mortality. This study aimed to assess the correlation between serum PAG levels and AS in kidney transplantation (KT) patients, potentially uncovering new insights into the cardiovascular risks in this population. In this study, 100 KT patients were included. Carotid-femoral pulse wave velocity (cfPWV) was measured, and patients with cfPWV > 10 m/s were categorized as the AS group. Serum PAG levels were assessed using liquid chromatography-tandem mass spectrometry. Thirty KT patients (30.0%) exhibited AS, with higher percentages of diabetes mellitus, older age, and elevated levels of systolic blood pressure, serum fasting glucose, and PAG than the control group. After adjusting for factors significantly associated with AS by multivariate logistic regression analysis, serum PAG, age, fasting glucose levels, and systolic blood pressure were independent factors associated with AS. Furthermore, PAG levels had a negative correlation with the estimated glomerular filtration rate and a positive correlation with cfPWV values. Serum PAG levels are positively associated with cfPWV values and are a biomarker of AS in KT patients.

Mediating effect of fat mass, lean mass, blood pressure and insulin resistance on the associations of accelerometer-based sedentary time and physical activity with arterial stiffness, carotid IMT and carotid elasticity in 1574 adolescents.

This study examined the mediating effect of total body fat mass, lean mass, blood pressure (BP) and insulin resistance on the associations of sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous PA (MVPA) with carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT) and carotid elasticity in 1574 adolescents from the Avon Longitudinal Study of Parents and Children birth cohort, UK. ST, LPA and MVPA were assessed with ActiGraph accelerometer. ST and LPA were sex-categorised in tertiles as low (reference), moderate and high, while MVPA was categorised as <40 min/day (reference), 40-<60 min/day and ≥60 min/day. cfPWV, cIMT and carotid elasticity were measured with Vicorder and ultrasound. Fat mass and lean mass were assessed with dual-energy X-ray absorptiometry and homeostatic model assessment of insulin resistance (HOMA-IR) was computed. Mediation analyses structural equation models and linear mixed-effect models adjusted for cardiometabolic and lifestyle factors were conducted. Among 1574 adolescents [56.2% female; mean (SD) age 15.4 (0.24) years], 41% males and 17% females accumulated ≥60 min/day of MVPA. Higher ST was associated with lower cIMT partly mediated by lean mass. Higher LPA (standardized ß = -0.057; [95% CI -0.101 to -0.013; p = 0.014]) and the highest LPA tertile were associated with lower cfPWV. BP had no significant mediating effect movement behaviour relations with vascular indices. Lean mass partially mediated associations of higher MVPA with higher cIMT (0.012; [0.007-0.002; p = 0.001], 25.5% mediation) and higher carotid elasticity (0.025; [0.014-0.039; p = 0.001], 28.1% mediation). HOMA-IR mediated the associations of higher MVPA with higher carotid elasticity (7.7% mediation). Engaging in ≥60 min/day of MVPA was associated with higher carotid elasticity. In conclusion, higher LPA was associated with lower arterial stiffness, but higher MVPA was associated with thicker carotid wall explained by higher lean mass.

Physical activity and arterial stiffness: is body fat a mediator?

PURPOSE: Physical activity (PA) and body fat percentage (%BF) are independently associated with arterial stiffness, but it has not been explored if there is an associative pathway among these variables. This study examined whether %BF mediates the relationship between PA or sedentary behavior levels with arterial stiffness. METHODS: Fifty adults (1:1 men:women; age 28 ± 11 year) had carotid-femoral pulse wave velocity (CF-PWV) measured by applanation tonometry, %BF by bioelectrical impedance, and PA levels by accelerometry. Accelerometer data determined minutes per day spent in sedentary, light, moderate-to-vigorous physical activity (MVPA), and Total PA. RESULTS: Pearson correlation indicated statistically significant associations among age, %BF, CF-PWV, MVPA, and Total PA (r = 0.34-0.65, p < 0.05). Sedentary and light PA were not associated with CF-PWV. Mediation analysis indicated significant total effects of MVPA (ß = - 0.34, p = 0.044) and age (ß = 0.65, p < 0.001) on CF-PWV. %BF mediated the relationship between Total PA and CF-PWV due to indirect effect of Total PA on %BF (ß = - 0.34, p = 0.02) and %BF on CF-PWV (ß = 0.44, p = 0.002), and partially mediated the relationship between age and CF-PWV (ß = 0.54, p < 0.001). Total PA retained its significant effect on %BF (ß = - 0.28, p = 0.04) and the effect of %BF on CF-PWV remained significant (ß = 0.26, p = 0.03), despite age having a significant effect on both %BF (ß = 0.31, p = 0.023) and CF-PWV (ß = 0.54, p < 0.001). CONCLUSIONS: %BF mediated the relationship between Total PA and arterial stiffness, even after accounting for age. Engagement in more Total PA may help to reduce %BF, resulting in decreased arterial stiffness.

Plethysmograph-Based Self-Assessment Device for Carotid-Femoral Pulse Wave Velocity Measurement: A Pilot Usability Study.

Arterial stiffness, a proxy of vascular aging is an important marker of cardiovascular events and mortality, independent of traditional risk factors. The aortic or carotid-femoral pulse wave velocity (cf-PWV) is the gold standard for determining arterial stiffness. Measuring arterial stiffness can help identify people who are at risk early on. State-of-the-art devices, majorly employing applanation tonometry at the carotid site, demand extensive skill, are costly, and are not intended for out-of-clinic use. However, a device that is suitable for homecare and primary health settings would facilitate primordial care. To address this gap, we have developed a novel easy-to-use, fully automated, and affordable photoplethysmography-based device for measuring cf-PWV. An in-vivo study on 25 subjects was conducted to investigate the device's usability by comparing self and expert-performed measurements, and by quantifying the user experience (score out of 5). A strong correlation (r = 0.88) and a statistically insignificant bias indicated the measurement reproducibility in self-versus expert-performed measurements. An average usability score of 3.98 ± 0.83 given by the participants showed the convenience and ease of use of the device. The results demonstrate the feasibility and reliability of using the device by inexperienced operators, even when newly introduced. Future clinical studies are in progress to assess the device's accuracy in comparison to gold-standard reference equipment.Clinical Relevance-This pilot study revealed the device's potential to offer a user-friendly solution for home care and other non-hospital settings.

Serum Trimethylamine N-Oxide Level Is Positively Associated with Aortic Stiffness Measured by Carotid-Femoral Pulse Wave Velocity in Patients Undergoing Maintenance Hemodialysis.

Trimethylamine N-oxide (TMAO) is a biomarker that is effective in predicting major adverse cardiovascular (CV) events. Age-related vascular problems are significantly affected by aortic stiffness (AS), which is independently linked to CV morbidity and mortality. This study aimed to determine the association between serum TMAO levels and carotid-femoral pulse wave velocity (cfPWV) in patients receiving hemodialysis (HD) therapy. In total, 115 patients with HD were enrolled in this study. The AS group included patients whose cfPWV was >10 m/s. Using high-performance liquid chromatography and mass spectrometry, the levels of serum TMAO were measured. The AS group included 42 (36.5%) patients, and compared with the non-AS group, the rates of diabetes, hypertension, older age, systolic blood pressure, serum glucose, and TMAO levels were high. In the multivariate logistic regression analysis, serum TMAO and age were independently linked with AS after correcting for the factors significantly associated with AS. Following multivariate stepwise linear regression analysis, serum TMAO in these individuals was found to be strongly correlated with cfPWV values (p < 0.001). In patients on chronic HD, serum TMAO level is an independent measure of AS and strongly correlated with cfPWV.

Association of estimated carotid-femoral pulse wave velocity with frailty in middle-aged and older adults with cardiometabolic disease.

PURPOSE: The prevalence of frailty in individuals with cardiometabolic disease (CMD) has become a growing concern in public health. The purpose of this study was to investigate the association between estimated pulse wave velocity (ePWV) and frailty in middle-aged and older adults with CMD. METHODS: We analyzed data from 23,313 non-institutionalized adults with CMD from the National Health and Nutrition Examination Survey 2003-2018. Frailty status was determined using the frailty index, and logistic regression models were used to assess the association of ePWV with frailty risk. Multivariable logistic regression and propensity-score matching (PSM) were used to adjust for potential confounders. The restricted cubic spline regression model was used to evaluate the non-linear association between ePWV and frailty risk. RESULTS: After adjusting for potential confounding factors, we found that each one m/s increase in ePWV was associated with a 15% higher risk of frailty (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.12 to 1.18, P < 0.001). After PSM, the association remained significant (OR = 1.05, 95% CI 1.03 to 1.08, P < 0.001). The logistic models with restricted cubic splines showed a non-linear dose-response association, with the risk of frailty increasing more rapidly when ePWV exceeded 9.5 m/s. CONCLUSIONS: The findings of this study suggest that a higher level of ePWV is associated with an increased risk of frailty in middle-aged and older adults with CMD, and may serve as a viable alternative to directly measured cfPWV.

Effects of body positions on arterial stiffness as assessed by pulse wave velocity.

BACKGROUND: Assessing arterial stiffness through pulse wave velocity (PWV) usually requires participants to be in a supine position. If this position is not feasible, adjustments such as tilting the bed or bending the knees may be made. The Vicorder device also recommends tilting the upper body to prevent jugular vein interference in the recorded carotid pulse. OBJECTIVE: To examine the impact of varying body positions on PWV. METHODS: Seventy adults were studied in the fully supine (0°) to 40° upper body tilted-up positions with and without knee bend. Carotid-femoral PWV (cfPWV) was measured using two different testing devices (Omron VP-1000plus and Vicorder) and brachial-ankle PWV (baPWV) was measured using Omron. RESULTS: cfPWV measured at 10° tilt-up was not different from 0° position while baPWV increased significantly from 10°. Elevations in cfPWV were 7% at 20° and 15% at 40° compared with 0° position. Knee bend did not affect cfPWV but decreased baPWV at each angle ( P  < 0.05). Jugular vein interference on the Vicorder was observed in 78% of participants in supine position, decreasing as body angle increased (7% at 30°). However, cfPWV values measured by Vicorder were consistent with those obtained by Omron even with jugular vein interference. CONCLUSION: Arterial stiffness assessed by PWV increased gradually and significantly in semi-Fowler's position ≥20°. Knee bend decreased baPWV but did not seem to affect cfPWV. PWV should be measured in supine position if possible. If the supine posture is not tolerated, knee bend followed by a slight incline position may be recommended.

Associations of habitual physical activity and carotid-femoral pulse wave velocity; a systematic review and meta-analysis of observational studies.

The aim of this review was to understand the association between habitual physical activity (hPA) and carotid-femoral pulse wave velocity (cfPWV) in an ostensibly healthy adult population. Searches were performed in MEDLINE Web of Science, SPORTDiscus and CINAHL databases published up to 01/01/2022 (PROSPERO, Registration No: CRD42017067159). Observational English-language studies assessing the relationship between cfPWV and hPA (measured via self-report or device-based measures) were considered for inclusion in a narrative synthesis. Studies were excluded if studying specific disease. Studies were further included in pooled analyses where a standardised association statistic for continuous hPA and cfPWV was available. 29 studies were included in narrative synthesis, of which 18 studies provided sufficient data for pooled analyses, totalling 15,573 participants. A weak, significant, negative correlation between hPA and cfPWV was observed; partial r = -0.08 95%CI [-0.15, -0.01]; P = 0.045. Heterogeneity was high (I2 = 94.5% P<0.001). Results did not differ across sub-group analyses, however the high heterogeneity within pooled analyses was largely explained by studies utilizing self-reports of PA exposures, being of poor methodological quality or providing only univariate analyses. Overall this systematic review identified a weak negative beneficial association between hPA and cfPWV suggesting that higher levels of hPA benefit vascular health even amongst an asymptomatic population. However, the variation in PA metrics reported (restricting ability to complete meta-analysis), and the heterogeneity within pooled analyses suggests that findings should be interpreted with a degree of caution. The development of methods to precisely quantify day-to-day movement behaviours should support future high-quality research in this field.

Temporal longitudinal associations of carotid-femoral pulse wave velocity and carotid intima-media thickness with resting heart rate and inflammation in youth.

We examined the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) with the risk of elevated resting heart rate (RHR) and high-sensitivity C-reactive protein (hsCRP). We studied 3,862 adolescents, mean age 17.7 (SD 0.3 yr), followed-up for 7 yr until age 24.5 (0.7) yr, from the Avon Longitudinal Study of Parents and Children, UK. RHR, fasting plasma hsCRP, cfPWV, and cIMT were repeatedly assessed and analyzed using logistic regression, linear mixed-effect, and structural equation models adjusting for important covariates. Among 3,862 adolescents [2,143 (55.5%) female], 10% and 44% were at moderate-to-high risk of elevated RHR and hsCRP at 24.5 yr, respectively. Higher cfPWV at 17.7 yr was associated with elevated RHR risk at follow-up [odds-ratio (OR) 1.58 (CI 1.20-2.08); P = 0.001], whereas cIMT at 17.7 yr was associated with elevated hsCRP risk [OR 2.30 (1.18-4.46); P = 0.014] at follow-up, only among females. In mixed model, 7-yr progression in cfPWV was directly associated with 7-yr increase in RHR [effect-estimate 6 beats/min (1-11); P = 0.017] and hsCRP. cIMT progression was associated with 7-yr increase in RHR and hsCRP. In cross-lagged model, higher cfPWV at 17.7 yr was associated with higher RHR (ß = 0.06, standard error = 3.85, P < 0.0001) at 24.5 yr but RHR at 17.7 yr was unassociated with cfPWV at 24.5 yr. Baseline cIMT or RHR was unassociated with either outcome at follow-up. Higher hsCRP at 17.7 yr was associated with higher cfPWV and cIMT at 24.5 yr. In conclusion, adolescent arterial stiffness but not cIMT appears to precede higher RHR in young adulthood, whereas elevated hsCRP in adolescence preceded higher cfPWV and cIMT.NEW & NOTEWORTHY Higher arterial stiffness but not carotid-intima media thickness in adolescence preceded higher resting heart rate in young adulthood, however, elevated high sensitivity C-reactive protein in adolescence preceded higher arterial stiffness and carotid intima-thickness in young adulthood in the temporal causal path. Low-grade inflammation during adolescence may be causally associated with the development of subclinical arteriosclerosis and atherosclerosis in young adulthood.

Comparison of brachial-ankle pulse wave velocity and carotid-femoral pulse wave velocity in association with albuminuria in a community of Beijing: a cross-sectional study.

This study was performed to investigate and compare the association of albuminuria with the brachial-ankle pulse wave velocity (baPWV) and carotid-femoral pulse wave velocity (cfPWV) in a community-based population in Beijing. Subjects were enrolled from a follow-up survey conducted in 2018 from an atherosclerosis cohort in Shijingshan district, Beijing, China. The baPWV and cfPWV were measured using a BP-203 RPE III arteriosclerosis detection device and PulsePen, respectively. Albuminuria was defined as a urinary albumin-creatinine ratio of ≥30 mg/g. A multivariate logistic regression model was used to evaluate the impacts of different PWV measurements on the prevalence of albuminuria. In total, 5605 subjects were included in the analyses. Their mean age was 62.22 ± 7.55 years, and the prevalence of albuminuria was 8.22%. In the multivariate logistic regression model adjusted for potential covariates, both baPWV (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03-1.10; P < 0.001) and cfPWV (OR, 1.07; 95% CI, 1.01-1.14; P = 0.018) were significantly associated with albuminuria. Furthermore, when baPWV and cfPWV were entered into the logistic regression model simultaneously, only baPWV was significantly associated with albuminuria using either continuous value (OR, 1.05; 95% CI, 1.01-1.10; P = 0.007) or classified into quartiles (highest vs. lowest value group: OR, 1.55; 95% CI, 1.01-2.37; P for trend = 0.019). Both cfPWV and baPWV were positively associated with albuminuria, while baPWV had a stronger relationship than cfPWV. Thus, baPWV measurement could be considered for the purpose of community health screening.

Estimation of carotid-femoral pulse wave velocity from finger photoplethysmography signal.

Objective. This project compared a new method to estimate the carotid-femoral pulse wave velocity (cf-PWV) to the gold-standard cf-PWV technique.Approach. The cf-PWV was estimated from the pulse transit time (FPS-PTT) calculated by processing the finger photoplethysmographic signal of Finapres (FPS) and subject's height only (brief mode) as well as along with other variables (age, heart rate, arterial pressure, weight; complete mode). Doppler ultrasound cf-PWVs and FPS-PTTs were measured in 90 participants equally divided into 3 groups (18-30; 31-59; 60-79 years). Predictions were performed using multiple linear regressions (MLR) and with the best regression model identified by using MATLAB Regression Learner App. A validation set approach (60 training datasets, 30 testing datasets; VSA) and leave-one-out cross-validation (LOOCV) were used.Main results. With MLR, the discrepancies were: 0.01 ± 1.21 m s-1(VSA) and 0.001 ± 1.11 m s-1(LOOCV) in brief mode; -0.02 ± 0.83 m s-1(VSA) and 0.001 ± 0.84 m s-1(LOOCV) in complete mode. Using a linear support vector machine model (SVM) in brief mode, the discrepancies were: 0.01 ± 1.19 m s-1(VSA) and -0.01 ± 1.06 m s-1(LOOCV). Using an Exponential Gaussian process regression model (GPR) in complete mode, the discrepancies were: -0.03 ± 0.79 m s-1(VSA) and 0.01 ± 0.75 m s-1(LOOCV).Significance. The cf-PWV can be estimated by processing the FPS-PTT and subjects' height only, but the inclusion of other variables improves the prediction performance. Predictions through MLR qualify as acceptable in both brief and complete modes. Predictions via linear SVM in brief mode improve but still qualify as acceptable. Interestingly, predictions through Exponential GPR in complete mode improve and qualify as excellent.

Disparities between determinants of impaired vascular structure and function in young people with primary hypertension: a systematic review.

OBJECTIVE: Early effects of primary hypertension on arterial structure and function in children and young people (CYP) and their determinants remain elusive. We aimed to review independent determinants of carotid intima-media thickness (cIMT), carotid wall cross-sectional area (WCSA) and carotid-femoral pulse wave velocity (cfPWV) in CYP with primary hypertension. METHODS: We performed a systematic review of studies reporting multivariable analysis of cfPWV, cIMT and WCSA in CYP (up to 25 years of age) with primary hypertension. Literature search was performed in PubMed database and 13, 12 and two articles including 3860 (age range 4-25 years, 50% male individuals), 2038 children (5-25 years, 55% male individuals) and 136 children (5-17 years, 85% male individuals) were selected for final analysis of cfPWV, cIMT and WCSA, respectively. RESULTS: Ninety and 86% of the studies reported higher cfPWV and cIMT in CYP with elevated blood pressure (BP) compared with normotensive controls. Different indices of BP were positively associated with cfPWV in 92% of studies, whereas BMI showed association in 31%. Carotid IMT associated with BP indices in 50% and with BMI in 25% of the studies. WCSA was studied longitudinally and its improvement associated with decrease in measures of central obesity. CONCLUSION: We found a disparity between the determinants of structural and functional impairment of arterial tree in CYP with primary hypertension. In contrast to cIMT and WCSA, increase of cfPWV is almost exclusively determined by BP.

Estimation of central pulse wave velocity from radial pulse wave analysis.

BACKGROUND AND OBJECTIVE: Arterial stiffness, commonly assessed by carotid-femoral pulse wave velocity (cfPWV), is an independent biomarker for cardiovascular disease. The measurement of cfPWV, however, has been considered impractical for routine clinical application. Pulse wave analysis using a single pulse wave measurement in the radial artery is a convenient alternative. This study aims to identify pulse wave features for a more accurate estimation of cfPWV from a single radial pulse wave measurement. METHODS: From a dataset of 140 subjects, cfPWV was measured and the radial pulse waveform was recorded for 30 s twice in succession. Features were extracted from the waveforms in the time and frequency domains, as well as by wave separation analysis. All-possible regressions with bootstrapping, McHenry's select algorithm, and support vector regression were applied to compute models for cfPWV estimation. RESULTS: The correlation coefficients between the measured and estimated cfPWV were r = 0.81, r = 0.81, and r = 0.8 for all-possible regressions, McHenry's select algorithm, and support vector regression, respectively. The features selected by all-possible regressions are physiologically interpretable. In particular, the amplitude ratio of the diastolic peak to the notch of the radial pulse waveform (Rn,dr,P) is shown to be correlated with cfPWV. This correlation was further evaluated and found to be independent of wave reflections using a dataset (n = 3,325) of simulated pulse waves. CONCLUSIONS: The proposed method may serve as a convenient surrogate for the measurement of cfPWV. Rn,dr,P is associated with aortic pulse wave velocity and this association may not be dependent on wave reflection.

Improving the accuracy and robustness of carotid-femoral pulse wave velocity measurement using a simplified tube-load model.

Arterial stiffness, as measured by pulse wave velocity, for the early non-invasive screening of cardiovascular disease is becoming ever more widely used and is an independent prognostic indicator for a variety of pathologies including arteriosclerosis. Carotid-femoral pulse wave velocity (cfPWV) is regarded as the gold standard for aortic stiffness. Existing algorithms for cfPWV estimation have been shown to have good repeatability and accuracy, however, further assessment is needed, especially when signal quality is compromised. We propose a method for calculating cfPWV based on a simplified tube-load model, which allows for the propagation and reflection of the pulse wave. In-vivo cfPWV measurements from 57 subjects and numerical cfPWV data based on a one-dimensional model were used to assess the method and its performance was compared to three other existing approaches (waveform matching, intersecting tangent, and cross-correlation). The cfPWV calculated using the simplified tube-load model had better repeatability than the other methods (Intra-group Correlation Coefficient, ICC = 0.985). The model was also more accurate than other methods (deviation, 0.13 ms-1) and was more robust when dealing with noisy signals. We conclude that the determination of cfPWV based on the proposed model can accurately and robustly evaluate arterial stiffness.

Brachial-ankle pulse wave velocity as a measurement for increased carotid intima-media thickness: A comparison with carotid-femoral pulse wave velocity in a Chinese community-based cohort.

Carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) act as two most frequently applied indicators to evaluate arterial stiffness. Limited studies have systematically compared the relationships between cfPWV/baPWV and increased carotid intima-media thickness (cIMT). This study aimed to investigate the associations of the two PWV indices with cIMT in a Chinese community-based population. A total of 6026 Chinese participants from an atherosclerosis cohort were included in our analysis. Increased cIMT was defined as the maximum of cIMT > 0.9 mm in end-systolic period of carotid artery. Mean (SD) cfPWV and baPWV were 8.55±1.83  and 16.79±3.35 m/s, respectively. The prevalence of increased cIMT was 59.58%. In multivariable logistic regression, both PWVs were independently associated with increased cIMT after adjustment for various confounders (for 1 m/s increase of cfPWV: OR = 1.07, 95% CI: 1.02-1.11; for 1 m/s increase of baPWV: OR = 1.03, 95% CI: 1.00-1.05). The highest cfPWV and baPWV quartile groups had higher prevalence of increased cIMT when compared with the lowest quartile groups (for cfPWV: OR = 1.28, 95% CI: 1.06-1.55; for baPWV: OR = 1.23, 95% CI: 1.00-1.50). However, when both PWVs were added into multivariable model simultaneously, only cfPWV was associated with odds of increased cIMT. Subgroup analyses further showed cfPWV was more strongly associated with increased cIMT than baPWV in males, participants aged ≥65 years, and those with other cardiovascular risk factors. In conclusion, both cfPWV and baPWV are associated with increased cIMT in a Chinese community-based population. Furthermore, cfPWV is more strongly correlated with increased cIMT compared to baPWV.

Prognostic Value of Changes in Aortic Stiffness for Cardiovascular Outcomes and Mortality in Resistant Hypertension: a Cohort Study.

The prognostic importance of changes in aortic stiffness for the occurrence of adverse cardiovascular outcomes and mortality has never been investigated in patients with resistant hypertension. We aimed to evaluate it in a prospective cohort of 442 resistant hypertension individuals. Changes in aortic stiffness were assessed by 2 carotid-femoral pulse wave velocity (CF-PWV) measurements performed over a median time interval of 4.7 years. Multivariate Cox analysis examined the associations between changes in CF-PWV (evaluated as continuous variables and categorized into quartiles and as increased/persistently high or reduced/persistently low) and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular/all-cause mortalities. During a median follow-up of 4.1 years after the second CF-PWV measurement, there were 49 total CVEs (42 major adverse CVEs) and 53 all-cause deaths (32 cardiovascular). As continuous variables, increments in absolute and relative changes in CF-PWV were associated with higher risks of CVEs and major adverse CVEs occurrence, but not of mortality. Divided into quartiles of CF-PWV changes, risks increased in the third and fourth quartile subgroups in relation to the reference first quartile subgroup (those with greatest CF-PWV reductions) for all outcomes. Patients who either increased or persisted with high CF-PWV had excess risks of cardiovascular morbidity/mortality, with hazard ratios ranging from 2.7 to 3.0, in relation to those who reduced or persisted with low CF-PWV values. In conclusion, reducing or preventing progression of aortic stiffness was associated with significant cardiovascular protection in patients with resistant hypertension, suggesting that it may be an additional clinical target of antihypertensive treatment.

Differential Effects of Electronic Hookah Vaping and Traditional Combustible Hookah Smoking on Oxidation, Inflammation, and Arterial Stiffness.

BACKGROUND: Traditional hookah smoking has grown quickly to become a global tobacco epidemic. More recently, electronic hookahs (e-hookahs)-vaped through traditional water pipes-were introduced as healthier alternatives to combustible hookah. With combustible tobacco smoking, oxidative stress, inflammation, and vascular stiffness are key components in the development and progression of atherosclerosis. The comparable effects of hookah are unknown. RESEARCH QUESTION: What is the differential acute effect of e-hookah vaping vs combustible hookah smoking on oxidation, inflammation, and arterial stiffness? STUDY DESIGN AND METHODS: In a randomized crossover design study, among a cohort of 17 healthy young adult chronic hookah smokers, we investigated the effect of e-hookah vaping and hookah smoking on measures of conduit arterial stiffness, including carotid-femoral pulse wave velocity (PWV), augmentation index-corrected for heart rate before and after a 30-min exposure session. We assessed a panel of circulating biomarkers indicative of inflammation and oxidants and measured plasma nicotine and exhaled carbon monoxide (CO) levels before and after the sessions. RESULTS: e-Hookah vaping tended to lead to a larger acute increase in PWV than hookah smoking (mean ± SE: e-hookah, +0.74 ± 0.12 m/s; combustible hookah, +0.57 ± 0.14 m/s [P < .05 for both]), indicative of large artery stiffening. Compared with baseline, only e-hookah vaping induced an acute increase in augmentation index (e-hookah, +5.58 ± 1.54% [P = .004]; combustible hookah, +2.87 ± 2.12% [P = not significant]). These vascular changes were accompanied by elevation of the proinflammatory biomarkers high-sensitivity C-reactive protein, fibrinogen, and tumor necrosis factor α after vaping (all P < .05). No changes in biomarkers of inflammation and oxidants were observed after smoking. Compared with baseline, exhaled CO levels were higher after smoking than after vaping (+36.81 ± 6.70 parts per million vs -0.38 ± 0.22 parts per million; P < .001), whereas plasma nicotine concentrations were comparable (+6.14 ± 1.03 ng/mL vs +5.24 ± 0.96 ng/mL; P = .478). INTERPRETATION: Although advertised to be "safe," flavored e-hookah vaping exerts injurious effects on the vasculature that are, at least in part, mediated by inflammation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03690427; URL: www.clinicaltrials.gov.