The Impact of Chemotherapy on Arterial Stiffness and Ventricular-Arterial Coupling in Women with Breast Cancer.

BACKGROUND: The cardiac toxicity of chemotherapy for breast cancer is not uncommon and has been associated with elevated morbidity and mortality. In the present study, we assessed the impact of chemotherapy on cardiovascular function by assessing the cardio-ankle vascular index (CAVI), global longitudinal strain (GLS) and ventricular-arterial coupling (VAC: CAVI/GLS ratio) in chemotherapy-treated women. METHODS: This prospective study enrolled 78 women with breast cancer who were receiving anthracycline-based chemotherapy +/- anti-HER2 therapy (trastuzumab +/- pertuzumab). Forty-one age-matched healthy women served as controls. We comparatively evaluated left ventricular ejection fraction (LVEF), CAVI, GLS and VAC, between the chemotherapy and control groups. We also assessed their changes over time (baseline, 3-month and 6-month time point) and their independent association with the incidence of cancer therapy-related cardiovascular dysfunction (CTRCD) in the chemotherapy group. RESULTS: In comparison to healthy controls, women receiving chemotherapy presented with significantly higher GLS (from -21.02 ± 2.09% to -19.01 ± 2.81%, p < 0.001) and VAC (-0.36 ± 0.06 to -0.41 ± 0.11, p < 0.001). The presence of CTRCD was associated with a further increase in GLS and CAVI and a significant decline in LVEF and VAC compared to CTRCD-free women (p < 0.001). Baseline, CAVI, GLS and VAC were independently associated with CTRCD development during follow-up. CONCLUSION: Women with breast cancer undergoing chemotherapy displayed abnormal levels of CAVI, VAC and GLS, compared to healthy individuals. Those effects on VAC and CAVI were more exaggerated among women with CTRCD, implicating their potential use to refine screening and therapeutic strategies for this specific population.

Age-Specific Approach to Arterial Stiffness Prediction in Apparently Healthy Patients.

Background: The high prevalence of traditional cardiovascular risk factors among the patients without cardiovascular disease (CVD) allows us to predict an increase in cardiovascular morbidity rate in the future. Arterial stiffness is one of the most important predictors and pathogenetic mechanisms of CVD development. The aim of our study was to evaluate the predictive differences of age-related and age-independent (universal) cardio-ankle vascular index (CAVI) reference values for detecting increased arterial stiffness in individuals without CVD. Methods: The study included 600 patients (43% men and 57% women, mean age 36.0 ± 18.3 years). All the patients underwent anthropometric measurements with obesity markers evaluation, assessment of arterial stiffness by sphygmomanometry. To create predictive models, we used universal and age-related CAVI thresholds: ≥ 9.0 (CAVI≥ 9) and CAVIAge according to the "Consensus of Russian experts on the evaluation of arterial stiffness in clinical practice". Results: In the < 50 years group, both the CAVIAge and CAVI≥ 9 models were significant (CAVIAge: b = 4.8, standard error b (st.err.b) = 0.27, P < 0.001; CAVI≥ 9: b = 3.2, st.err.b = 1.6, P < 0.001). The CAVIAge model demonstrated high sensitivity and specificity (> 70%) compared to the CAVI≥ 9 model (sensitivity 62%, specificity 58%). In the receiver operating characteristic (ROC) curve analysis, the CAVIAge model had a significantly higher area under the ROC curve (AUC) = 0.802 than the CAVI≥ 9 model: AUC = 0.674. In the ≥ 50 years group, both models were significant: CAVIAge (b = 2.6, st.err.b = 1.13, P < 0.001) and CAVI≥ 9 (b = 5.3, st.err.b = 0.94, P < 0.001). Both models demonstrated high sensitivity and specificity (> 70%). When ROC curves were analyzed for the CAVIAge model, the AUC value of 0.675 was significantly lower when compared to the CAVI≥ 9 model (AUC = 0.787, P = 0.031). Conclusions: In the < 50 years group, the model based on age-specific CAVI thresholds has the higher predictive value, sensitivity, and specificity for identifying individuals with increased arterial stiffness. In contrast, in the ≥ 50 years group, a predictive model using a universal threshold value of CAVI≥ 9 has advantages.

Impact of Cardio-Ankle Vascular Index on Future Cancer in Patients With Coronary Artery Disease.

Background: Cardiovascular risk factors are associated with increased risk of future cancer. However, the relationship between quantitative parameters of atherosclerosis and future cancer risk is unclear. Methods and Results: A total of 1,057 consecutive patients with coronary artery disease was divided into 2 groups according to the cutoff value of the cardio-ankle vascular index (CAVI) derived by receiver operating characteristic curve analysis: low CAVI group (CAVI <8.82; n=487), and high CAVI group (CAVI ≥8.82; n=570). Patients in the high CAVI group were older and had a higher prevalence of diabetes, chronic kidney disease, anemia and history of stroke compared with patients in the low CAVI group. There were 141 new cancers during the follow-up period. The cumulative incidence of new cancer was significantly higher in the high CAVI group than in the low CAVI group (P=0.001). In a multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of new cancer diagnosis (hazard ratio 1.62; 95% confidence interval 1.11-2.36; P=0.012). In the analysis of individual cancer types, high CAVI was associated with lung cancer (hazard ratio 2.85; 95% confidence interval 1.01-8.07; P=0.049). Conclusions: High CAVI was associated with the risk of future cancer in patients with coronary artery disease.

Prognostic Value of Cardio-Ankle Vascular Index for Cardiovascular and Kidney Outcomes: Systematic Review and Meta-Analysis.

Background: Arterial stiffness causes cardiovascular disease and target-organ damage. Carotid-femoral pulse wave velocity is regarded as a standard arterial stiffness metric. However, the prognostic value of cardio-ankle vascular index (CAVI), which is mathematically corrected for blood pressure, remains understudied. Objectives: The purpose of this study was to determine the association of CAVI with cardiovascular and kidney outcomes. Methods: PubMed, Scopus, and Web of Science were searched until May 6, 2023, for longitudinal studies reporting the association of CAVI with mortality, cardiovascular events (CVEs) (including death, acute coronary syndromes, stroke, coronary revascularization, heart failure hospitalization), and kidney function decline (incidence/progression of chronic kidney disease, glomerular filtration rate decline). Random-effects meta-analysis was performed. Studies were assessed with the "Quality in Prognostic Studies" tool. Results: Systematic review identified 32 studies (105,845 participants; follow-up range: 12-148 months). Variable cutoffs were reported for CAVI. The risk of CVEs was higher for high vs normal CAVI (HR: 1.46 [95% CI: 1.22-1.75]; P < 0.001; I2 = 41%), and per SD/unit CAVI increase (HR: 1.30 [95% CI: 1.20-1.41]; P < 0.001; I2 = 0%). Among studies including participants without baseline cardiovascular disease (primary prevention), higher CAVI was associated with first-time CVEs (high vs normal: HR: 1.60 [95% CI: 1.15-2.21]; P = 0.005; I2 = 65%; HR per SD/unit increase: 1.28 [95% CI: 1.12-1.47]; P < 0.001; I2 = 18%). There was no association between CAVI and mortality (HR = 1.31 [0.92-1.87]; P = 0.130; I2 = 53%). CAVI was associated with kidney function decline (high vs normal: HR = 1.30 [1.18-1.43]; P < 0.001; I2 = 38%; HR per SD/unit increase: 1.12 [95% CI: 1.07-1.18]; P < 0.001; I2 = 0%). Conclusions: Higher CAVI is associated with incident CVEs, and this association is present in the primary prevention setting. Elevated CAVI is associated with kidney function decline.

Predictive significance of cardio ankle vascular index for the assessment of cardiovascular risk in hypertensive patients: A systematic review.

Cardio-ankle vascular index (CAVI) is an innovative indicator of large-artery stiffness, which is evaluated by the pulse wave velocity (PWV) measurement. Mortality and morbidity due to cardiovascular diseases among the general public with high-risk conditions such as hypertension are usually associated with arterial stiffness. CAVI modelizes the hazard of future cardiovascular events with standard risk factors. Additionally, the "European Society of Hypertension and Cardiology" included the aortic PWV assessment in managing hypertension in their updated guidelines in 2007. We conducted this systematic review to collect, summarize, and evaluate the evidence from relevant reported studies. A literature search of four databases was conducted comprehensively until February 2024. Cardiovascular events are the primary outcome of interest in this study, cardiovascular events that have been defined as major adverse cardiac events include "heart failure", "stroke", "myocardial infarction", "cardiovascular deaths", "stable angina pectoris", "coronary revascularization", and "unstable angina pectoris". We included five studies with a 11 698 sample size in this systematic review. All five prospective studies investigated composite cardiovascular events as an outcome. Three of them revealed a statistically significant prediction ability of CAVI to assess Cardiovascular disease (CVD) risk. Further analysis is required. Current evidence is insufficient to confirm the predictive power of CAVI in the assessment of cardiovascular risk in hypertensive patients. CAVI is modestly associated with incidents of CVD risk. It is necessary to conduct further studies to assess CAVI concerning CVD predictor measures in the masses and nations other than Asia.

Usefulness of Serum Testosterone Concentration and Skin Autofluorescence as Coronary Risk Markers in Male Patients With Type 2 Diabetes Mellitus.

Background: No studies have reported simultaneous evaluation of the two coronary risk markers of testosterone and skin autofluorescence (SAF) as a marker of advanced glycation end products in patients with type 2 diabetes mellitus (T2DM) at present. This study aimed to clarify the clinical significance of both indicators as risk markers of coronary artery disease (CAD), including the association and background factors between testosterone and SAF in male patients with T2DM. Methods: This study enrolled 162 male patients with T2DM (CAD: n = 35). Testosterone was evaluated by serum total testosterone concentration (T-T). Various analyses related to T-T and SAF as coronary risk markers were performed. Results: T-T was significantly lower, and SAF was significantly higher in patients with CAD than in patients with non-CAD. A significant negative correlation was found between T-T and SAF (r = -0.45, P < 0.001), and the correlation was stronger in patients with CAD than in patients with non-CAD (non-CAD, r = -0.27, P = 0.003; CAD, r = -0.51, P < 0.001). However, both T-T and SAF had significant associations with triglyceride-glucose index as an insulin resistance marker and cardio-ankle vascular index as an arterial function marker. Multiple regression analysis revealed that both T-T and SAF were selected as independent variables to the presence of CAD as a dependent variable. However, the odds ratio increased due to the merger of two coronary risk markers, low T-T and high SAF (odds ratio: one risk marker: 3.24, 95% confidence interval: 1.01 - 10.50, P = 0.045; two risk markers: 13.22, 95% confidence interval: 3.41 - 39.92, P < 0.001). Conclusions: The results of this cross-sectional study indicate that T-T and SAF are closely related in CAD patients with T2DM. It also shows that insulin resistance and arterial dysfunction are in the background of both indicators. Additionally, not only are both indicators independent coronary risk markers, but the overlap of both indicators increases their weight as coronary risk markers.

Difference in right and left cardio-ankle vascular index as a useful marker for evaluation of leg ischemia in patients with lower extremity arterial disease.

OBJECTIVES: Cardio-ankle vascular index (CAVI) is a blood pressure-independent measure of heart-ankle pulse wave velocity and is used as an indicator of arterial stiffness. However, there is a paradox that CAVI is inversely associated with leg ischemia in patients with lower extremity arterial disease (LEAD). The aim of this study was to clarify the significance of the absolute value of left and right difference in CAVI (diff-CAVI). METHODS: The subjects were 165 patients with LEAD who had received medication therapy. Relationships between diff-CAVI and leg ischemia were investigated. Leg ischemia was evaluated by decrease in leg arterial flow using ankle-brachial index (ABI) and by symptoms using the Rutherford classification. RESULTS: There was a significant inverse correlation between diff-CAVI and ABI. The odds ratio for low ABI of the 3rd versus 1st tertile groups of diff-CAVI was 7.03 with a 95% confidence interval of 2.71 ∼ 18.22. In ROC analysis, the cutoff value of diff-CAVI for low ABI was 1.05 with a sensitivity of 61.1% and a specificity of 87.1%. The median of diff-CAVI was significantly higher in subjects with grade 2 of the Rutherford classification than in subjects with its grade 1. CONCLUSIONS: diff-CAVI showed an inverse association with ABI and a positive association with symptoms of leg ischemia. Thus, diff-CAVI is thought to be a useful indicator of leg ischemia in LEAD patients.

Association between the Serum Soluble Urokinase Plasminogen Activator Receptor and Peripheral Arterial Stiffness According to the Cardio-Ankle Vascular Index in Patients Undergoing Kidney Transplantation.

Background: High soluble urokinase plasminogen activator receptor (suPAR) levels are correlated with cardiovascular (CV) disease. Arterial stiffness is associated with aging-related vascular diseases and is an independent risk factor for CV morbidity and mortality. It can be measured by the cardio-ankle vascular index (CAVI). We evaluated the association between serum suPAR levels and arterial stiffness according to the CAVI in kidney transplantation (KT) recipients. Methods: In this study, 82 patients undergoing KT were enrolled. Serum suPAR levels were analyzed using an enzyme immunoassay. The CAVI was measured using a plethysmograph waveform device, and patients with a CAVI of ≥ 9.0 were assigned to the peripheral arterial stiffness (PAS) group. Results: Twenty KT patients (24.4%) had PAS, were of older age (p = 0.042), and had higher serum triglyceride (p = 0.023) and suPAR levels (p < 0.001) than the normal group. After adjusting for factors significantly associated with PAS by multivariate logistic regression analysis, serum suPAR levels (odds ratio [OR] 1.072, 95% confidence interval (CI) 1.023-1.123; p = 0.004) were independently associated with PAS in KT patients. The logarithmically transformed suPAR level (log-suPAR) was also positively correlated with the left or right CAVI values (all p < 0.001) from the results of the Spearman correlation analysis in KT patients. Conclusions: Serum suPAR levels are positively associated with left or right CAVI values and are independently associated with PAS in KT patients.

Habitual Regular Coffee Consumption and Arterial Stiffness: Data From the 3rd Pamela Survey.

BACKGROUND: We evaluated whether chronic coffee consumption affects arterial stiffness, assessed by cardio-ankle vascular index (CAVI). METHODS: In 514 subjects, aged 66.6 ±â€…9.9 years (mean ±â€…SD), recruited in the 3rd follow-up of the PAMELA study, subdivided into 3 groups according to the daily intake of regular coffee (0, 1-2, and ≥3 cups/day), we measured CAVI and clinic, ambulatory blood pressure (BP), and other variables. RESULTS: The 3 groups displayed similar age, gender, metabolic, and renal profile. Clinic and ambulatory BPs were similar in the 3 groups, this being the case for CAVI (0 cup: 9.1 ±â€…1.8, 1-2 cups: 9.5 ±â€…2.3, and ≥3 cups: 9.2 ±â€…2.1 m/s, P = NS). No significant gender difference in CAVI and in participants under antihypertensive treatment was detected. CONCLUSIONS: Our data show that chronic coffee consumption leaves unaffected arterial stiffness in the general population, this being the case in subgroups. The neutral vascular impact of coffee may favor the absence of any significant BP effect of habitual coffee intake.

Predictive value of Systematic Coronary Risk Evaluation 2-Diabetes risk model and arterial stiffness for cardiovascular events in the Asian population with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Individuals with diabetes are at high risk of developing cardiovascular events. The present study investigated the predictive value of the cardio-ankle vascular index (CAVI) when added to the Systematic Coronary Risk Evaluation 2-Diabetes (SCORE2-Diabetes) risk algorithm to predict cardiovascular events in the Asian population. MATERIALS AND METHODS: The SCORE2-Diabetes risk was assessed in 1,502 patients with diabetes, aged 40-69 years. Then, we further stratified each 10-year risk category with a CAVI value of 9.0. The primary outcomes (composite of all causes of death, myocardial infarction, stroke and hospitalization for heart failure) were assessed over 5 years. RESULTS: The mean age of the population was 59.8 ± 6.4 years. The proportion of 10-year risk according to the SCORE2-Diabetes risk of low, moderate, high and very high risk identified at 7.2, 30.0, 27.2 and 35.6%, respectively. The mean CAVI value was 8.4 ± 1.4, and approximately 35.4% of the patients had CAVI ≥9.0. The SCORE2-Diabetes risk algorithm independently predicted the primary outcomes in patients with diabetes (hazard ratio 1.18, 95% confidence interval [CI] 1.13-1.22), whereas CAVI did not (hazard ratio 1.03, 95% CI 0.89-1.18). The C-index for the primary outcomes of the SCORE2-Diabetes risk algorithm alone was 0.72 (95% CI 0.67-0.77). The combination of SCORE2-Diabetes and CAVI, both in the continuous value and risk groups, did not improve discrimination (C-index 0.72, 95% CI 0.67-0.77 and 0.68, 95% CI 0.64-0.74, respectively). CONCLUSIONS: Adding the CAVI to the SCORE2-Diabetes risk algorithm did not improve individual risk stratification in patients with diabetes.

Altered Arterial Stiffness, Ventricular-Arterial Coupling and Troponin Levels in Patients with Systemic Lupus Erythematosus.

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVDs), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC), and high-sensitivity cardiac troponin I (hsTnI) in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex-matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTnI between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTnI within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS, and hsTnI levels, while VAC was significantly reduced (p < 0.001). Furthermore, SLE patients with active disease (SELENA-SLEDAI ≥ 4) exhibited higher levels of CAVI and troponin than those with inactive disease (p < 0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTnI in the SLE cohort. Conclusions: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

Dynamics of the State of Arterial Stiffness as a Possible Pathophysiological Factor of Unfavorable Long-Term Prognosis in Patients after Coronary Artery Bypass Grafting.

The aim of this study was to examine the long-term prognostic value of changes in the cardio-ankle vascular index (CAVI) within a year after coronary artery bypass grafting (CABG). METHODS: Patients with coronary artery disease (n = 251) in whom CAVI was assessed using the VaSera VS-1000 device before and one year after CABG. Groups with improved CAVI or worsened CAVI were identified. We assessed the following events at follow-up: all-causes death, myocardial infarction, and stroke/transient ischemic attack. RESULTS: All-causes death was significantly more common in the group with worsened CAVI (27.6%) than in the group with CAVI improvement (14.8%; p = 0.029). Patients with worsened CAVI were more likely to have MACE, accounting for 42.2% cases, compared with patients with CAVI improvement, who accounted for 24.5%; p = 0.008. Worsened CAVI (p = 0.024), number of shunts (p = 0.006), and the presence of carotid stenosis (p = 0.051) were independent predictors of death from all causes at 10-year follow-up after CABG. The presence of carotid stenosis (p = 0.002) and the group with worsened CAVI after a year (p = 0.008) were independent predictors of the development of the combined endpoint during long-term follow-up. CONCLUSIONS: Patients with worsening CAVI one year after CABG have a poorer prognosis at long-term follow-up than patients with improved CAVI. Future research would be useful to identify the most effective interventions to improve CAVI and correspondingly improve prognosis.

Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study.

BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

Hypertension-specific association of cardio-ankle vascular index with subclinical left ventricular function in a Chinese population: Danyang study.

The association of cardio-ankle vascular index (CAVI), with subclinical cardiac dysfunction in hypertensive patients is unclear. We aim to examine their relationship in hypertensive patients compared with that in normotensive subjects. Our study included 1887 subjects enrolled from Danyang between 2018 and 2019. CAVI was measured using VaSera VS-1500A device. We performed conventional echocardiography to measure ejection fraction (EF) and E/A, tissue Doppler to measure mitral annular early diastolic velocities (e'), and speckle-tracking to estimate left ventricular (LV) global longitudinal strain (GLS). LV mass index (76.3, 80.0, and 84.0 g/m2), and E/e' (7.6, 8.2, and 8.8) were increased and GLS (21.1, 21.0, and 20.4%), E/A (1.2, 1.0, and 0.8) and e' velocity (11.2, 9.4, and 8.2 cm/s) was decreased from tertiles 1-3 of CAVI on unadjusted analyses (P < .001). After adjustment for covariates, GLS, E/A, and e' were still significantly decreased from tertiles 1-3 of CAVI (P ≤ .04). Further sensitive analyses revealed a similar association pattern for diastolic function but not systolic function. Compared with the lowest tertile, subjects with a top tertile of CAVI were at higher risk of subclinical LV systolic dysfunction in hypertensive patients (OR = 2.61; P = .005). Increased CAVI is associated with worse subclinical diastolic function. However, this relationship of CAVI to subclinical systolic function was more prominent in hypertensive patients.

Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

BACKGROUND: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). METHODS: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). MEASUREMENTS: cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. RESULTS: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant. CONCLUSIONS: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity.

An Increase in Vascular Stiffness Is Positively Associated With Mitochondrial Bioenergetics Impairment of Peripheral Blood Mononuclear Cells in the Older Adults.

The cardio-ankle vascular index (CAVI) is a noninvasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a noninvasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the older adults.. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand between 2017 and 2018. A total of 1 640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into 3 groups based on their CAVI values as high (CAVI ≥ 9), moderate (9 > CAVI ≥ 8), and low (CAVI < 8), in which each group comprised 702, 507, and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.

CAVI (Cardio-Ankle Vascular Index) as an independent predictor of hypertensive response to exercise.

OBJECTIVES: Hypertensive response to exercise (HRE) is related to the development of future hypertension, cardiovascular morbidity, and mortality, independent of resting blood pressure. We hypothesized that arterial stiffness as measured by cardio-ankle vascular index (CAVI) could be an independent predictor of HRE. MATERIALS AND METHODS: Retrospective chart review of patients participated in the preventive health program at the Bangkok Heart Hospital who underwent both CAVI and treadmill stress testing on the same day between June and December 2018 were performed. Variables for the prediction of HRE were analyzed using univariate analysis, and significant variables were entered into multiple logistic regression. An ROC curve was created to test the sensitivity and specificity of CAVI as a predictor of HRE. RESULTS: A total of 285 participants (55.1% female) were enrolled in this study. There were 58 patients (20.4%) who met the HRE definition (SBP > 210 mmHg in males, SBP > 190 mmHg in females, or DBP > 110 mmHg in both males and females), with a mean age of 46.4 12.8 years. In univariate analysis, age, systolic blood pressure at rest, diastolic blood pressure at rest, pulse pressure at rest, diabetes mellitus, hypertension, dyslipidemia, history of beta-blocker, and CAVI results were statistically significant. Multiple logistic regression revealed that CAVI and systolic blood pressure were statistically significant predictors of HRE with OR of 5.8, 95%CI: 2.9-11.7, P < 0.001 and OR 1.07, 95%CI: 1.03-1.10, P = 0.001 respectively. ROC curve analysis of the CAVI revealed an AUC of 0.827 (95%CI: 0.76-0.89, p < 0.001), and the sensitivity and specificity of cut-point CAVI > 8 were 53% and 92%, respectively. CONCLUSION: This study demonstrated that CAVI is an independent predictor of hypertensive response to exercise. Additionally, the findings suggest that CAVI > 8 can be a valuable tool in identifying individuals at risk for hypertensive responses during exercise.

Association of Nonalcoholic Fatty Liver Disease with Arterial Stiffness and its Metabolomic Profiling in Japanese Community-Dwellers.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites. METHODS: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted. RESULTS: NAFLD was positively associated with CAVI (coefficients [95% Confidence intervals (CI)]=0.23 [0.09-0.37]; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI. CONCLUSIONS: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.