Short-term vascular responses to spring and fall daylight savings time shifts.

Daylight saving time (DST) is a Western biannual time transition, setting the clock back 1 h in the fall and forward 1 h in the spring. There is an epidemiological link between DST and acute myocardial infarction risk in the first week following the spring shift; however, the mechanisms underlying the effect of DST on cardiovascular function remain unclear. The purpose of this study was to explore the short-term cardiovascular changes induced by fall and spring shifts in DST in a convenience sample of healthy adults. We hypothesized that spring, but not fall, DST shifts would acutely increase central pulse wave velocity, the gold standard measurement of central arterial stiffness. Twenty-one individuals (fall: n = 10; spring: n = 11) participated in four visits, occurring 1 wk before and at +1, +3, and +5 days after spring and fall time transitions. Central, brachial, and radial pulse wave velocity as well as carotid augmentation index were assessed with applanation tonometry. Sleep quality and memory function were assessed via questionnaire and the Mnemonic Similarities Task, respectively. Neither fall or spring transition resulted in changes to cardiovascular variables (carotid-femoral pulse wave velocity, carotid-brachial pulse wave velocity, carotid-radial pulse wave velocity, heart rate, mean arterial pressure, or augmentation index), sleep quality, or cognitive function (all P > 0.05). Our findings do not provide evidence that DST shifts influence cardiovascular outcomes in healthy adults. This study emphasizes the need for further research to determine the mechanisms of increased cardiovascular disease risk with DST that help explain epidemiological trends.NEW & NOTEWORTHY The debate of whether to abolish daylight savings time (DST) is, in part, motivated by the population-level increase in all-cause mortality and incidence of cardiovascular events following DST; however, there is an absence of data to support a physiological basis for risk. We found no changes in pulse wave velocity or augmentation index during the subacute window of DST. Large multisite trials are necessary to address the small, but meaningful, effects brought on by a societal event.

Arterial stiffness mediates the association between age and processing speed at low levels of microvascular function in humans across the adult lifespan.

The function of micro- and macrovessels within the peripheral vasculature has been identified as a target for the investigation of potential cardiovascular-based promoters of cognitive decline. However, little remains known regarding the interaction of the micro- and macrovasculature as it relates to cognitive function, especially in cognitively healthy individuals. Therefore, our purpose was to unravel peripheral factors that contribute to the association between age and processing speed. Ninety-nine individuals (51 men, 48 women) across the adult life span (19-81 yr) were used for analysis. Arterial stiffness was quantified as carotid-femoral pulse-wave velocity (cfPWV) and near-infrared spectroscopy assessed maximal tissue oxygenation (Sto2max) following a period of ischemia. Processing speed was evaluated with Trail Making Test (TMT) Parts A and B. Measures of central (cPP) and peripheral pulse pressure (pPP) were also collected. Moderated mediation analyses were conducted to determine contributions to the age and processing speed relation, and first-order partial correlations were used to assess associations while controlling for the linear effects of age. A P ≤ 0.05 was considered statistically significant. At low levels of Sto2max, there was a significant positive (b = 1.92; P = 0.005) effect of cfPWV on time to completion on TMT part A. In addition, cPP (P = 0.028) and pPP (P = 0.027) remained significantly related to part A when controlling for age. These results suggested that the peripheral microvasculature may be a valuable target for delaying cognitive decline, especially in currently cognitively healthy individuals. Furthermore, we reinforced current evidence that pulse pressure is a key endpoint for trials aimed at preventing or delaying the onset of cognitive decline.NEW & NOTEWORTHY Arterial stiffness partially mediates the association between age and processing speed in the presence of low microvascular function, as demarcated by maximum tissue oxygenation following ischemia. Central and peripheral pulse pressure remained associated with processing speed even after controlling for age. Our findings were derived from a sample that was determined to be cognitively healthy, which highlights the potential for these outcomes to be considered during trials aimed at the prevention of cognitive decline.

Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study.

OBJECTIVES: There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD). METHODS: In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55-65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV. RESULTS: Copeptin was associated with TBI (ß-0.0020, CI-0.0035- (-0.0005), p = 0.010) and aPWV (ß 0.023, CI 0.002-0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking. CONCLUSIONS: Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders. TRIAL REGISTRATION:  ClinicalTrials.gov identifier NCT010497377.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes. METHODS: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied. RESULTS: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed. CONCLUSION: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D. TRIAL REGISTRATION: ISRCTN91419926.

Paravascular fluid dynamics reveal arterial stiffness assessed using dynamic diffusion-weighted imaging.

Paravascular cerebrospinal fluid (pCSF) surrounding the cerebral arteries within the glymphatic system is pulsatile and moves in synchrony with the pressure waves of the vessel wall. Whether such pulsatile pCSF can infer pulse wave propagation-a property tightly related to arterial stiffness-is unknown and has never been explored. Our recently developed imaging technique, dynamic diffusion-weighted imaging (dynDWI), captures the pulsatile pCSF dynamics in vivo and can explore this question. In this work, we evaluated the time shifts between pCSF waves and finger pulse waves, where pCSF waves were measured by dynDWI and finger pulse waves were measured by the scanner's built-in finger pulse oximeter. We hypothesized that the time shifts reflect brain-finger pulse wave travel time and are sensitive to arterial stiffness. We applied the framework to 36 participants aged 18-82 years to study the age effect of travel time, as well as its associations with cognitive function within the older participants (N = 15, age > 60 years). Our results revealed a strong and consistent correlation between pCSF pulse and finger pulse (mean CorrCoeff = 0.66), supporting arterial pulsation as a major driver for pCSF dynamics. The time delay between pCSF and finger pulses (TimeDelay) was significantly lower (i.e., faster pulse propagation) with advanced age (Pearson's r = -0.44, p = 0.007). Shorter TimeDelay was further associated with worse cognitive function in the older participants. Overall, our study demonstrated pCSF as a viable pathway for measuring intracranial pulses and encouraged future studies to investigate its relevance with cerebrovascular functions.

Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery.

BACKGROUND: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic. METHODS: Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery). RESULTS: Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014). CONCLUSIONS: Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.

Evaluation of high-density lipoprotein-bound long non-coding RNAs in subjects with familial hypercholesterolaemia.

BACKGROUND: Long non-coding RNAs (lncRNAs) could be attractive circulating biomarkers for cardiovascular risk stratification in subjects at high atherosclerotic cardiovascular disease risk such as familial hypercholesterolaemia (FH). Our aim was to investigate the presence of lncRNAs carried by high-density lipoprotein (HDL) in FH subjects and to evaluate the associations of HDL-lncRNAs with lipoproteins and mechanical vascular impairment assessed by pulse wave velocity (PWV). METHODS: This was a retrospective observational study involving 94 FH subjects on statin treatment. Biochemical assays, HDL purification, lncRNA and PWV analyses were performed in all subjects. RESULTS: LncRNA HIF1A-AS2, LASER and LEXIS were transported by HDL; moreover, HDL-lncRNA LEXIS was associated with Lp(a) plasma levels (p < .01). In a secondary analysis, the study population was stratified into two groups based on the Lp(a) median value. The high-Lp(a) group exhibited a significant increase of PWV compared to the low-Lp(a) group (9.23 ± .61 vs. 7.67 ± .56, p < .01). While HDL-lncRNA HIF1A-AS2 and LASER were similar in the two groups, the high-Lp(a) group exhibited a significant downregulation of HDL-lncRNA LEXIS compared to the low-Lp(a) group (fold change -4.4, p < .0001). Finally, Lp(a) and HDL-lncRNA LEXIS were associated with PWV (for Lp(a) p < .01; for HDL-lncRNA LEXIS p < .05). CONCLUSIONS: LncRNA HIF1A-AS2, LASER and LEXIS were transported by HDL; moreover, significant relationships of HDL-lncRNA LEXIS with Lp(a) levels and PWV were found. Our study suggests that HDL-lncRNA LEXIS may be useful to better identify FH subjects with more pronounced vascular damage.

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.

Association of aortic stiffness early post myocardial infarction with left ventricular remodelling.

BACKGROUND: Adverse left ventricular (LV) remodelling after myocardial infarction is associated with heart failure. We investigated whether aortic stiffness during acute ST-segment elevation myocardial infarction is associated with LV remodelling at long-term follow-up. METHODS: In 109 patients within 48 h of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (a) carotid to femoral pulse wave velocity (PWV), (b) LV global longitudinal strain (GLS) and left atrial strain using speckle-tracking echocardiography, (c) PWV/GLS ratio as a surrogate marker of ventricular-arterial interaction, and (d) LV end-diastolic and end-systolic volumes. A > 15% decrease from the baseline in LV end-systolic volume at 2-year follow-up was considered as a criterion of reverse LV remodelling. RESULTS: Compared with baseline, all patients had reduced PWV, LV end-diastolic and end-systolic volumes while PWV/GLS, GLS and reservoir left atrial strain were improved (p < .05) after 2 years. Baseline values of PWV, GLS, PWV/GLS ratio and reservoir left atrial strain were associated with percentage change of LV end-systolic volume at 2 years (p < .05). Multivariable analysis revealed that lower baseline values of PWV and a less impaired GLS and PWV/GLS were independently associated with reverse LV remodelling at 2 years with a C-statistic of .748, .711 and .787, respectively. CONCLUSION: Aortic stiffness early post-infarction determines LV remodelling after 2 years of the ischemic event despite post successful revascularization. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT03984123, 30/04/2020.

Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function.

BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2). METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined. RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 µmol·h-1·kg-1 compared with 0.39 ± 0.10 µmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004). CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

Feasibility, Repeatability, and Correlation to Lung Function of Phase-Resolved Functional Lung (PREFUL) MRI-derived Pulmonary Artery Pulse Wave Velocity Measurements.

BACKGROUND: Pulse wave velocity (PWV) in the pulmonary arteries (PA) is a marker of vascular stiffening. Currently, only phase-contrast (PC) MRI-based options exist to measure PA-PWV. PURPOSE: To test feasibility, repeatability, and correlation to clinical data of Phase-Resolved Functional Lung (PREFUL) MRI-based calculation of PA-PWV. STUDY TYPE: Retrospective. SUBJECTS: 79 (26 female) healthy subjects (age range 19-78), 58 (24 female) patients with chronic obstructive pulmonary disease (COPD, age range 40-77), 60 (33 female) patients with suspected pulmonary hypertension (PH, age range 28-85). SEQUENCE: 2D spoiled gradient echo, 1.5T. ASSESSMENT: PA-PWV was measured from PREFUL-derived cardiac cycles based on the determination of temporal and spatial distance between lung vasculature voxels using a simplified (sPWV) method and a more comprehensive (cPWV) method including more elaborate distance calculation. For 135 individuals, PC MRI-based PWV (PWV-QA) was measured. STATISTICAL TESTS: Intraclass-correlation-coefficient (ICC) and coefficient of variation (CoV) were used to test repeatability. Nonparametric tests were used to compare cohorts. Correlation of sPWV/cPWV, PWV-QA, forced expiratory volume in 1 sec (FEV1 ) %predicted, residual volume (RV) %predicted, age, and right heart catheterization (RHC) data were tested. Significance level α = 0.05 was used. RESULTS: sPWV and cPWV showed no significant differences between repeated measurements (P-range 0.10-0.92). CoV was generally lower than 15%. COPD and PH patients had significantly higher sPWV and cPWV than healthy subjects. Significant correlation was found between sPWV or cPWV and FEV1 %pred. (R = -0.36 and R = -0.44), but not with RHC (P-range -0.11 - 0.91) or age (P-range 0.23-0.89). Correlation to RV%pred. was significant for cPWV (R = 0.42) but not for sPWV (R = 0.34, P = 0.055). For all cohorts, sPWV and cPWV were significantly correlated with PWV-QA (R = -0.41 and R = 0.48). DATA CONCLUSION: PREFUL-derived PWV is feasible and repeatable. PWV is increased in COPD and PH patients and correlates to airway obstruction and hyperinflation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Acute inflammation elicits decreased blood pressure but similar arterial stiffness in young African American adults.

African Americans (AA) have a higher risk for cardiovascular disease (CVD) as compared to their White (W) counterparts. CVD is characterized by increased blood pressure (BP), arterial stiffness and systemic inflammation. An acute inflammatory stimulus may explain physiological manifestations responsible for amplified CVD in AA that are not apparent at rest. The purpose of this study was to evaluate central and peripheral BP, central and local arterial stiffness, and indices of pulse wave morphology in young healthy AA and W participants in response to acute inflammation. Concentrations of the inflammatory cytokine interleukin-6 (IL-6) and measures of central and peripheral BP, central arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)), local carotid arterial stiffness (ß-stiffness, elastic modulus (Ep)), and indices of pulse wave morphology were assessed in 28 participants (21 ± 2 years, AA: n = 11) at baseline (BL), 24 h and 48 h post-inflammation. Changes in IL-6 concentrations (ΔIL-6) were significantly greater at 24 h as compared to 48 h post-inflammation (0.652 ± 0.644 vs. -0.146 ± 0.532 pg/µl, P ≤ 0.0001). Among AA participants, central and peripheral diastolic BP were significantly decreased at 24 h post-inflammation as compared to BL (aortic diastolic BP: -4 ± 4 mmHg, P = 0.016; brachial diastolic BP: -4 ± 4 mmHg, P = 0.014). AA participants also experienced a significant decrease in central and peripheral mean arterial BP at 48 h post-inflammation as compared to BL (aortic mean arterial pressure: -4 ± 4 mmHg, P = 0.009; brachial mean arterial pressure: -4 ± 4 mmHg, P = 0.012). Despite haemodynamic changes, there were no differences in central or local carotid arterial stiffness or indices of pulse wave morphology.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank.

BACKGROUND: Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscles may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses. METHODS: Carotid-femoral pulse wave velocity (CF-PWV) and brachial and central pulse pressure were measured in 5676 participants of the FHS (Framingham Heart Study) without diabetes. We used Cox proportional hazards regression to evaluate the association of CF-PWV and pulse pressure with incident diabetes. We subsequently performed 2-sample Mendelian randomization analyses evaluating the associations of genetically predicted brachial pulse pressure with type 2 diabetes in the UKBB (United Kingdom Biobank). RESULTS: In FHS, individuals with higher CF-PWV were older, more often male, and had higher body mass index and mean arterial pressure compared to those with lower CF-PWV. After a median follow-up of 7 years, CF-PWV and central pulse pressure were associated with an increased risk of new-onset diabetes (per SD increase, multivariable-adjusted CF-PWV hazard ratio, 1.36 [95% CI, 1.03-1.76]; P=0.030; central pulse pressure multivariable-adjusted CF-PWV hazard ratio, 1.26 [95% CI, 1.08-1.48]; P=0.004). In United Kingdom Biobank, genetically predicted brachial pulse pressure was associated with type 2 diabetes, independent of mean arterial pressure (adjusted odds ratio, 1.16 [95% CI, 1.00-1.35]; P=0.049). CONCLUSIONS: Using prospective cohort data coupled with Mendelian randomization analyses, we found evidence supporting that greater LAS is associated with increased risk of developing diabetes. LAS may play an important role in glucose homeostasis and may serve as a useful marker of future diabetes risk.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Aortic Stiffness Is Independently Associated with Intracranial Carotid Artery Calcification in Patients with Ischemic Stroke.

INTRODUCTION: Intracranial carotid artery calcification (ICAC), as a strong contributor to the occurrence of ischemic stroke, might be present in the medial or intimal arterial layer. Traditional cardiovascular risk factors (CVRFs) are associated with ICAC; however, its association with new markers of vascular function is less understood. The paper aimed to evaluate the relationship between carotid-femoral pulse wave velocity (CF-PWV) and ICAC subtypes. METHODS: We enrolled 65 patients with ischemic stroke. CF-PWV, systolic, diastolic, mean blood pressure, and pulse pressure were measured within 6 ± 2 days after stroke onset, and CT was performed within 24 h. ICAC on the stroke site was classified by two methods: volume and score based. Tertiles of ICAC volume were determined, and low-grade ICAC (T1) was regarded as a reference. According to the score-based method, (dominant) medial and (dominant) intimal ICAC subtypes were determined. Data were analyzed with multivariate logistic regression. RESULTS: Medial and intimal ICAC subtypes were found in 34 (52%) and 24 (37%) patients, respectively. In 11% of patients, no ICAC calcifications were found. CF-PWV was higher in patients with high-grade ICAC (OR = 1.56, 95% CI = 1.03-2.35, p = 0.035). CF-PWV was higher in patients with the medial ICAC subtype (OR = 1.60, 95% CI = 1.00-2.55, p = 0.049) after adjustment for traditional CVRFs. CONCLUSION: Our study demonstrates that among patients with ischemic stroke, aortic stiffness is independently associated with ICAC and that medial ICAC, compared with intimal ICAC, is accompanied by more advanced aortic stiffness.

Update on the Use of Pulse Wave Velocity to Measure Age-Related Vascular Changes.

PURPOSE OF REVIEW: Pulse wave velocity (PWV) is an important and well-established measure of arterial stiffness that is strongly associated with aging. Age-related alterations in the elastic properties and integrity of arterial walls can lead to cardiovascular disease. PWV measurements play an important role in the early detection of these changes, as well as other cardiovascular disease risk factors, such as hypertension. This review provides a comprehensive summary of the current knowledge of the effects of aging on arterial stiffness, as measured by PWV. RECENT FINDINGS: This review highlights recent findings showing the applicability of PWV analysis for investigating heart failure, hypertension, and other cardiovascular diseases, as well as cerebrovascular diseases and Alzheimer's disease. It also discusses the clinical implications of utilizing PWV to monitor treatment outcomes, various challenges in implementing PWV assessment in clinical practice, and the development of new technologies, including machine learning and artificial intelligence, which may improve the usefulness of PWV measurements in the future. Measuring arterial stiffness through PWV remains an important technique to study aging, especially as the technology continues to evolve. There is a clear need to leverage PWV to identify interventions that mitigate age-related increases in PWV, potentially improving CVD outcomes and promoting healthy vascular aging.

Association Between Arterial Stiffness and New-Onset Heart Failure: The Kailuan Study.

BACKGROUND: Arterial stiffness (AS) was associated with heart failure (HF) in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account. Whether AS was independently associated with new-onset HF in community dwellers has not been fully investigated to date. METHODS: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity (baPWV) screening in 2010 to 2019 were included. They were free of HF and atrial fibrillation at baseline. The participants were allocated to 3 groups according to their baPWV values. Normal AS was defined as baPWV <1400 cm/s, borderline AS was defined as 1400≤baPWV<1800 cm/s, and elevated AS was defined as baPWV ≥1800 cm/s. Cox proportional hazard regression was used to calculate hazard ratios with 95% CIs of new-onset HF across different AS groups. RESULTS: A total of 40 064 participants were enrolled with a mean age of 48.81±12.67 years. During a mean 5.53 years of follow-up, 411 participants developed HF. Compared with the normal AS group, the hazard ratio (95% CI) for incident HF was 1.97 (1.36-2.86) for the borderline AS group and 2.24 (1.49-3.38) for the elevated AS group in the multivariable-adjusted model. For each 1 SD (359 cm/s) increase in baPWV, the hazard ratio (95% CI) for new-onset HF was 1.10 (1.02-1.20). CONCLUSIONS: AS was positively associated with a higher risk of new-onset HF independently of traditional risk factors, with a dose-responsive effect.

Regional and Global Aortic Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is commonly defined as localised aortic dilatation with a diameter > 30 mm. The pathophysiology of AAA includes chronic inflammation and enzymatic degradation of elastin, possibly increasing aortic wall stiffness and pulse wave velocity (PWV). Whether aortic stiffness is more prominent in the abdominal aorta at the aneurysm site is not elucidated. The aim of this study was to evaluate global and regional aortic PWV in patients with AAA. METHODS: Experimental study of local PWV in the thoracic descending and abdominal aorta in patients with AAA and matched controls. The study cohort comprised 25 patients with an AAA > 30 mm (range 36 - 70 mm, all male, age range 65 - 76 years) and 27 age and sex matched controls free of AAA. PWV was measured with applanation tonometry (carotid-femoral PWV, cfPWV) as well as a 4D flow MRI technique, assessing regional aortic PWV. Blood pressure and anthropometrics were measured. RESULTS: Global aortic PWV was greater in men with an AAA than controls, both by MRI (AAA 8.9 ± 2.4 m/s vs. controls 7.1 ± 1.5 m/s; p = .007) and cfPWV (AAA 11.0 ± 2.1 m/s vs. controls 9.3 ± 2.3 m/s; p = .007). Regionally, PWV was greater in the abdominal aorta in the AAA group (AAA 7.0 ± 1.8 m/s vs. controls 5.8 ± 1.0 m/s; p = .022), but similar in the thoracic descending aorta (AAA 8.7 ± 3.2 m/s vs. controls 8.2 ± 2.4 m/s; p = .59). Furthermore, PWV was positively associated with indices of central adiposity both in men with AAA and controls. CONCLUSION: PWV is higher in men with AAA compared with matched controls in the abdominal but not the thoracic descending aorta. Furthermore, aortic stiffness was linked with central fat deposition. It remains to be seen whether there is a causal link between AAA and increased regional aortic stiffness.

Associations of childhood diet quality scores with arterial stiffness and carotid artery intima-media thickness in adolescence/early adulthood: findings from the ALSPAC cohort.

This study examined the relationship between childhood diet quality and arterial stiffness and thickness during adolescence/early adulthood. Participants were from the Avon Longitudinal Study of Parents and Children (ALSPAC) with dietary data at ages 7, 10 and 13 years and pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) at ages 17 and/or 24 years. Diet quality (DQ) was assessed using five scores: a children's Mediterranean-style diet (C-rMED) Z-score, a children's Dietary Inflammatory Z-score (C-DIS), a DASH diet Z-score, a children's Eatwell Guide (C-EWG) Z-score reflecting UK dietary guidelines and a data-driven obesogenic Z-score. Adjusted regression models examined the associations between DQ scores at 7-13 years and PWV and cIMT at 17 and 24 years. In adjusted models, a high v. low Obesogenic Z-score at 7 and 10 years was associated with higher PWV at 17: ß 0.07 (95 % CI 0.01, 0.13) and ß 0.10 (95 % CI 0.04, 0.16), respectively. A high v. low C-rMED Z-score at 7 years was associated with lower PWV at 17 (ß -0.07; 95 % CI -0.14, -0.01). A high (more anti-inflammatory) vs low C-DIS Z-score at 10 years was associated with a lower PWV at 17 years: ß -0.06 (95 % CI -0.12, -0.01). No other associations were observed. In conclusion, an Obesogenic dietary pattern in childhood (7-10 years) was related to increased arterial stiffness, while Mediterranean-style and anti-inflammatory diets were related to decreased arterial stiffness in adolescence. This highlights the importance of establishing healthy dietary habits early in life to protect against vascular damage.