Effects of Aerobic Exercise Training on Cerebral Pulsatile Hemodynamics in Middle-aged Adults with Elevated Blood Pressure/Stage-1 Hypertension.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12 wks aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. 28 inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 d/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wks, while cardiorespiratory fitness (VO2peak) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wks. VO2peak increased 6% in AET and decreased 4% in CON (p<0.05). Proximal aortic compliance increased (p=0.04, partial η2=0.14) and aortic characteristic impedance decreased (p=0.02, partial η2=0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant (p=0.07, partial η2=0.11) compared to CON. Working memory reaction time improved with AET but not CON (p=0.02, partial η2=0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g. proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics.

Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents.

OBJECTIVES: Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. METHODS: Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1ß, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. RESULTS: There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. CONCLUSIONS: Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

A cost-effective, machine learning-driven approach for screening arterial functional aging in a large-scale Chinese population.

Introduction: An easily accessible and cost-free machine learning model based on prior probabilities of vascular aging enables an application to pinpoint high-risk populations before physical checks and optimize healthcare investment. Methods: A dataset containing questionnaire responses and physical measurement parameters from 77,134 adults was extracted from the electronic records of the Health Management Center at the Third Xiangya Hospital. The least absolute shrinkage and selection operator and recursive feature elimination-Lightweight Gradient Elevator were employed to select features from a pool of potential covariates. The participants were randomly divided into training (70%) and test cohorts (30%). Four machine learning algorithms were applied to build the screening models for elevated arterial stiffness (EAS), and the performance of models was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Fourteen easily accessible features were selected to construct the model, including "systolic blood pressure" (SBP), "age," "waist circumference," "history of hypertension," "sex," "exercise," "awareness of normal blood pressure," "eat fruit," "work intensity," "drink milk," "eat bean products," "smoking," "alcohol consumption," and "Irritableness." The extreme gradient boosting (XGBoost) model outperformed the other three models, achieving AUC values of 0.8722 and 0.8710 in the training and test sets, respectively. The most important five features are SBP, age, waist, history of hypertension, and sex. Conclusion: The XGBoost model ideally assesses the prior probability of the current EAS in the general population. The integration of the model into primary care facilities has the potential to lower medical expenses and enhance the management of arterial aging.

Influence of MAFLD and NAFLD on arterial stiffness: A longitudinal cohort study.

BACKGROUND AND AIMS: This cohort study investigated associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with risk of increase in arterial stiffness (AS), measured as brachial-ankle pulse wave velocity (baPWV). METHODS AND RESULTS: Participants who had health examinations between 2006 and 2019 were analyzed for fatty liver and increased baPWV using liver ultrasonography and automatic volume plethysmography device. Participants were classified based on presence of MAFLD or NAFLD and further divided into subgroups: no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD. Subgroups were additionally stratified by sex. Cox proportional hazard model was utilized to analyze the risk of developing baPWV ≥1400 cm/s in participants without baseline elevation of the baPWV. The NAFLD and MAFLD groups exhibited higher risks of increased baPWV (NAFLD: adjusted hazard ratio (aHR), 1.35 [95% CI, 1.29-1.42]; MAFLD: aHR, 1.37 [95% CI, 1.31-1.43]) compared to group without the conditions. Incidence of NAFLD or MAFLD were higher in men than in women but aHR of developing the increase in AS was higher in women. In subgroup analysis, the MAFLD-only group presented the strongest associations with increase in AS (aHR, 1.53 [95% CI, 1.43-1.64]), with the trend more pronounced in women than in men (Women, aHR, 1.63 [95% CI, 1.08-2.46]; Men, aHR 1.45 [95% CI, 1.35-1.56]). CONCLUSIONS: Both NAFLD and MAFLD are significantly associated with elevated AS. These associations tended to be stronger in MAFLD than in NAFLD, in women than in men.

Twenty-Four-Hour Ambulatory Blood Pressure Monitoring Parameters During Pregnancy: A Pilot Study.

Introduction: Maternal blood pressure (BP) is a critical cardiovascular marker with profound implications for maternal and fetal well-being, particularly in the detection of hypertensive disorders during pregnancy. Although conventional clinic-based BP (CBP) measurements have traditionvally been used, monitoring 24-hour ambulatory BP (ABP) has emerged as a more reliable method for assessing BP levels and diagnosing conditions such as gestational hypertension and preeclampsia/eclampsia. This study aimed to assess the feasibility and acceptability of 24-hour ABP monitoring in pregnant women and report on various ABP parameters, including ambulatory blood pressure variability (ABPV). Method: A prospective cross-sectional study design was employed, involving 55 multipara pregnant women with and without prior adverse pregnancy outcomes (APOs). The participants underwent baseline assessments, including anthropometrics, resting CBP measurements, and the placement of ABP and actigraphy devices. Following a 24-hour period with these devices, participants shared their experiences to gauge device acceptability. Pregnancy outcomes were collected postpartum. Results: Twenty-four-hour ABP monitoring before 20 weeks of gestation is feasible for women with and without prior APOs. Although some inconvenience was noted, the majority of participants wore the ABP monitoring device for the entire 24-hour period. Pregnant women who later experienced APOs exhibited higher 24-hour ABP and ABPV values in the early stages of pregnancy. Conclusion: The study highlights the potential benefits of 24-hour ABP monitoring as a valuable tool in prenatal care, emphasizing the need for further research in this area.

Functional capacity, physical activity, and arterial stiffness in patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a complex immune-mediated connective tissue disease, involving skin manifestations, vascular features, and organ-based complications that may affect functional capacity and physical activity. Functional capacity and physical activity are associated with arterial stiffness; however, this relationship has not been evaluated in patients with SSc. Therefore, the objective of this study was to investigate the association of functional capacity and physical activity with arterial stiffness in patients with SSc. METHODS: Sixty-five patients with SSc were enrolled in this cross-sectional study. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV). Functional capacity and physical activity were assessed with a six-min walk test (6MWT) and International Physical Activity Questionnaire-Short Form (IPAQ-SF), respectively. RESULTS: All participants were women, and the mean age was 54.91 ± 11.18 years. 6MWT distance and IPAQ-SF were inversely associated with cf-PWV in crude analysis (p < 0.05). The relationship between 6MWT distance and cf-PWV was maintained in the fully adjusted model (ß = - 0.007, 95% CI, - 0.013 to 0.000). Similarly, the association between IPAQ-SF and cf-PWV remained significant in the fully adjusted model (ß = - 0.001, 95% CI, - 0.002 to - 0.001). CONCLUSION: The present study indicates that functional capacity and self-reported physical activity are independently associated with arterial stiffness in patients with SSc. Exercise interventions targeted to increase functional capacity and physical activity may help to regulate arterial stiffness in patients with SSc. Key Points • Arterial stiffness is an independent predictor of cardiovascular risk. • SSc patients exhibit decreased exercise capacity and functional capacity. • The association of functional capacity and physical activity with arterial stiffness in patients with SSc is unknown. • Functional capacity and self-reported physical activity are independently associated with arterial stiffness in patients with SSc.

Serum metabolome perturbation in relation to noise exposure: Exploring the potential role of serum metabolites in noise-induced arterial stiffness.

Noise pollution has grown to be a major public health issue worldwide. We sought to profile serum metabolite expression changes related to occupational noise exposure by untargeted metabolomics, as well as to evaluate the potential roles of serum metabolites in occupational noise-associated arterial stiffness (AS). Our study involved 30 noise-exposed industrial personnel (Lipo group) and 30 noise-free controls (Blank group). The untargeted metabolomic analysis was performed by employing a UPLC-HRMS. The associations of occupational noise and significant differential metabolites (between Blank/Lipo groups) with AS were evaluated using multivariable-adjusted generalized linear models. We performed the least absolute shrinkage and selection operator regression analysis to further screen for AS's risk metabolites. We explored 177 metabolites across 21 categories significantly differentially expressed between Blank/Lipo groups, and these metabolites were enriched in 20 metabolic pathways. Moreover, 15 metabolites in 4 classes (including food, glycerophosphocholine, sphingomyelin [SM] and triacylglycerols [TAG]) were adversely associated with AS (all P < 0.05). Meanwhile, five metabolites (homostachydrine, phosphatidylcholine (PC) (32:1e), PC (38:6p), SM (d41:2) and TAG (45:1) have been proven to be useful predictors of AS prevalence. However, none of these 15 metabolites were found to have a mediating influence on occupational noise-induced AS. Our study reveals specific metabolic changes caused by occupational noise exposure, and several metabolites may have protective effects on AS. However, the roles of serum metabolites in noise-AS association remain to be validated in future studies.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

BACKGROUND: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. OBJECTIVE: This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. METHODS: At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. RESULTS: Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). CONCLUSIONS: In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

Extracellular Vesicles in Metabolic and Vascular Insulin Resistance.

BACKGROUND: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. SUMMARY: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. KEY MESSAGE: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.

Dose-response associations of triglyceride to high-density lipoprotein cholesterol ratio and triglyceride-glucose index with arterial stiffness risk.

BACKGROUND: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. METHODS: We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. RESULTS: For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01-1.23) and 1.78 (1.38-2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14-1.39) and 1.57 (1.36-1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with ß of 0.09 (95% CI 0.04-0.14) and 0.57 (95% CI 0.35-0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. CONCLUSIONS: High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness.

Arterial Stiffness Changes in Adult Cancer Patients Receiving Anticancer Chemotherapy: A Real-World Bicentric Experience.

Background Chemotherapy correlates to acute and long-term cardiotoxicity, is reflected clinically by myocardial and vascular endothelial dysfunction, and can cause cardiovascular complications. Thus, early diagnosis of cardiovascular disease in cancer patients undergoing anti-cancer treatment is necessary to enhance long-term survival. Our principal objective in this study was to discern the impact of specific anti-cancer chemotherapeutics and biologics on arterial stiffness alterations before and after the administration. Methods Conducted at Mustafa Bacha University Hospital, Algeria, the study focused on arterial stiffness in anti-cancer chemotherapy patients. Assessments included blood pressure, diabetes, and dyslipidemia, with precise measurements using validated systems, particularly pulse wave velocity (PWV). Various chemotherapy protocols were applied, and statistical analysis with R software (R Foundation for Statistical Computing, Vienna, Austria) maintained a significance level of p=0.05. Key outcomes centered on carotid-femoral PWV and secondary endpoints such as central and peripheral pressures and pulse pressure (PP). Univariate and bivariate analyses were conducted using appropriate statistical tests.  Results A comparative prospective observational study was completed on 58 patients (34 women and 24 men; mean age: 52.64 +/- 12.12 years) treated with anti-cancer chemotherapy agents. Our evaluation included a complete clinical exam, electrocardiogram, Doppler echocardiography, and applanation tonometry with arterial stiffness measurement using PWV. Patients presented significantly higher levels of carotid-femoral PWV, regardless of the chosen chemotherapy protocol, with no return to the initial level after one year of stopping treatment (p-value < 0.01). Moreover, this increase was more significant in patients with diabetes and hypertension and patients treated with monoclonal antibodies or intercalants.  Conclusion This prospective study shows that chemotherapy patients have elevated arterial stiffness, emphasizing the need to assess PWV and monitor cardiovascular risk factors. PP measurement with PWV could improve risk management.

Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

Deterioration of Kidney Function Is Affected by Central Arterial Stiffness in Late Life.

Cardiovascular diseases affect kidney function. The aim of this study was to investigate the possible associations between hemodynamic parameters and change in kidney function in individuals aged 75 years and older. Data on hemodynamics and blood and urine samples were collected at baseline and during one-year visits. Hemodynamics were split into two groups based on median values. Changes in the estimated glomerular filtration rate (eGFR) were investigated between low and high groups for each hemodynamic parameter using analysis of variance. Changes in the albumin-creatinine ratio (ACR) were examined as binary outcomes (large increase vs. stable) using logistic regression. The population consisted of 252 participants. Participants in the high central systolic blood pressure (cSBP) group had a greater decline in eGFR than participants in the low cSBP group (-6.3% vs. -2.7%, p = 0.006). Participants in the high aortic pulse wave velocity (aPWV) group had a greater decline in eGFR than those in the low aPWV group (-6.8% vs. -2.5%, p = 0.001). Other hemodynamic parameters were not associated with eGFR changes. Hemodynamics were not associated with changes in the ACR; aPWV and cSBP appear to be predictors for eGFR decline in older age; monitoring and treatment of elevated stiffness might be helpful in order to prevent kidney function decline.

Endothelial dysfunction influences augmented aortic hemodynamic responses to metaboreflex activation in postmenopausal women.

PURPOSE: Postmenopausal women experience augmented aortic hemodynamic responses to isometric handgrip (IHG) exercise and metaboreflex activation post-exercise muscle ischemia (PEMI). Relationships between endothelial function brachial artery flow-mediated dilation (FMD) and aortic stiffness carotid-femoral pulse wave velocity (cfPWV) with aortic pulsatile hemodynamics during IHG and PEMI have not been determined. The relationships between aortic hemodynamic responses to PEMI were evaluated. METHODS: Aortic blood pressure (BP), wave reflection, and pressure of forward (Pf) and backward (Pb) waves were measured using arterial tonometry at rest, IHG at 30% maximal force, and PEMI in 30 (15/group) postmenopausal women with low (≤ 4.5%) and normal (≥ 5.5%) FMD. Hemodynamic responses were analyzed as the change (Δ) from rest to the last minute of IHG and PEMI. RESULTS: Brachial and aortic systolic BP (SBP) responses to IHG were higher in the low vs normal FMD group (P < 0.05). Aortic SBP (Δ20 ± 8 vs Δ11 ± 7 mmHg), pulse pressure (PP) (Δ12 ± 8 vs Δ6 ± 4 mmHg), augmented pressure (AP) (Δ5 ± 3 vs Δ2 ± 2 mmHg), and Pb (Δ6 ± 4 vs Δ3 ± 2 mmHg) responses to PEMI were greater (P < 0.05) in women with low vs. normal FMD. FMD was negatively correlated with aortic SBP, PP, AP, and Pb (P < 0.05) responses to PEMI. cfPWV was not correlated with responses to PEMI. CONCLUSION: Endothelial dysfunction relates to augmented aortic pulsatile load during metaboreflex activation, which may increase cardiovascular risk in postmenopausal women.

Associations of cardiac function and arterial stiffness with cerebrovascular disease.

BACKGROUND: White matter hyperintensities (WMHs) represent diffuse small vessel disease implicating the cardiac, systemic, and cerebral vasculatures. As the brain may be the end-organ of cumulative vascular disease, and higher education is protective of both cardiovascular and brain health, we aim to clarify their intertwining relationships. METHODS: We evaluated participants (mean age = 64) from the UK Biobank with neuroimaging measures of WMHs, left ventricular ejection fraction (LVEF) quantified using cardiovascular MRI, and arterial stiffness index (ASI) quantified using finger photoplethysmography. We used multiple regression to evaluate the basic, independent, and interactive relationships of LVEF status (n = 27,512) and ASI (n = 33,584) with WMHs. Moderated mediation analysis was used to determine whether the relationship between LVEF status and WMH was mediated by ASI and moderated by education. RESULTS: Abnormal LVEF (ß = -0.082, p < 0.001) and higher ASI (ß = 0.02, p < 0.001) were associated with greater WMHs separately and independently, but not interactively. Moderated mediation analyses revealed that the relationship between abnormal LVEF and WMH was mediated by ASI, for individuals with lower education (ß = -0.004, p < 0.001). Abnormal LVEF was associated with lower cortical thickness in 16 predominantly frontotemporal and select parietal regions (FDR, q < 0.05). CONCLUSIONS: Cardiovascular dysfunction is associated with regional cerebral atrophy and may precipitate cerebrovascular disease via stiffening of systemic vasculatures, particularly for individuals with lower education. Integrative approaches to study biophysiological vascular systems can elucidate the complex interplay between biological and social determinants of brain and cerebrovascular health.

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.

Arterial stiffness progression in metabolic dysfunction-associated fatty liver disease subtypes: A prospective cohort study.

BACKGROUND AND AIMS: We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. METHODS AND RESULTS: Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups. Among the participants with a median follow-up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW-, lean- and DM-MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non-MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81-16.94), 25.33 (7.84-42.83) and 38.49 (27.88-49.10) in OW, lean and DM-MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10-1.95), 3.56 (1.72-5.40) and 3.94 (2.82-5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM-, lean-, OW with metabolic abnormalities (MA)-, and OW without MA-MAFLD. CONCLUSION: MAFLD, especially DM-MAFLD and lean-MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.

INCREASED DIAMETER AND STIFFNESS OF ELASTIC BUT NOT MUSCULAR ARTERIES IN MEN WITH ABDOMINAL AORTIC ANEURYSM.

It has been proposed that formation of abdominal aortic aneurysm (AAA) is part of a systemic arterial dilatative disease. However, arteries in the upper extremity are scarcely studied and it remains unclear whether both muscular and elastic arteries are affected by the proposed systemic arterial dilatation. The aim of this study was to investigate diameter and stiffness of muscular and elastic arteries in arterial branches originating from the aortic arch. Twenty-six men with AAA (69 ± 4 years) and fifty-seven men without AAA (70 ± 5 years) were included in the study. Ultrasound was used to examine the distal and proximal brachial artery, axillary artery, and common carotid artery (CCA), and measurement of diameter and diameter change were performed with wall-tracking software. Blood pressure measurements were used to calculate local arterial wall stiffness indices. The AAA cohort presented larger arterial diameters in the CCA and axillary artery after adjustment for body surface area (p=0.002, respectively), while the brachial artery diameters were unchanged. Indices of increased stiffness in CCA (e.g., lower distensibility, p=0.003) were seen in subjects with AAA, after adjustments for body mass index and mean arterial blood pressure. This study supports the theory of a systemic arterial dilating diathesis in in peripheral elastic, but not in muscular, arteries. Peripheral elastic arteries also exhibited increased stiffness, in analogy with findings in the aorta in AAA.

Association of pulse pressure and aortic root diameter in elderly Chinese patients with chronic heart failure.

Background: High pulse pressure (PP) and aortic root diameter (AoD) are hallmarks of arterial stiffness or vascular aging and they are considered as risk factors for age-related cardiovascular disease, including heart failure (HF). However, the relationship between PP and AoD in patients with heart failure (HF) is uncertain. This study aimed to evaluate the relationship between PP and AoD in the middle-aged and the elderly with HF. Methods: A total of 1,027 Chinese middle-aged and elderly patients with HF, including HF with reduced ejection fraction (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF) were included in this study. Pearson correlation analysis was used to evaluate the relationship between PP and AoD in the three types of HF. Multiple linear regression analysis was performed to assess the factors that affected AoD. Multivariate logistic regression was performed to determine the association between the PP level quartiles and AoD. The results were validated in an independent dataset included a total of 378 consecutive patients with HFrEF hospitalized at the Pingtan Branch of Fujian Medical University Union Hospital (Fujian, China). Results: There was a positive correlation between PP and AoD in the middle-aged and the elderly with HFrEF. Multiple linear regression analysis revealed that PP, age, and body mass index (BMI) were independently correlated with AoD in HFrEF patients. In multivariate logistic regression analysis, an increased risk of aortic root dilation was observed in the highest quartile of the PP level compared with the lowest quartile. Age significantly interacted with PP (p = 0.047). A significant association between PP levels and AoD was only observed in patients ≥ 65 years old, but not in patients < 65 years old. In the validation dataset, PP was independently related to AoD in patients with HFrEF (ß = 0.205, p = 0.001). Conclusions: PP level was independently and positively associated with AoD, especially in the elderly with HFrEF, but not in patients with HFmrEF and HFpEF. Arterial stiffening or vascular aging may play a certain role in the elderly HFrEF patients.

Home- vs gym-based exercise delivery modes of two multicomponent intensity training regimes on cardiorespiratory fitness and arterial stiffness in adults with intellectual and developmental disability during the COVID-19 pandemic - a randomized controlled trial.

Background: We compared the effects of home- vs gym-based delivery modes of two 8-week supervised multicomponent intensity training regimes on cardiorespiratory fitness and arterial stiffness in 17 adults with intellectual and developmental disability during the COVID-19 pandemic. Methods: Participants were assigned to sprint interval training or continuous aerobic training, both incorporating resistance training. The intervention started with 8-weeks of online training (M1-M2), 1-month of detraining, plus 8-weeks of gym-based training (M3-M4). Results: Peak oxygen uptake decreased from M1-M2 and increased from M2-M4. Central arterial stiffness decreased between M1-M2, and M1-M4, along with peripheral arterial stiffness. Central systolic blood pressure decreased from M1-M2 only with sprint interval training. Conclusion: Home-based training minimized the negative impact of the lockdown on central arterial stiffness and central blood pressure, but it did not match the benefits on cardiorespiratory fitness and peripheral arterial stiffness of a gym-based intervention, irrespective of the multicomponent intensity training regime. Registered in ClinicalTrials.gov NCT05701943.