Changes in the cardiovascular risk profile in children approaching kidney replacement therapy.

Background: Despite significant cardiovascular (CV) morbidity in children on dialysis and after kidney transplantation, data on the evolution of CV damage in children with chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) is unknown. Methods: The burden, progression, and predictors of CV damage before KRT onset were explored in two prospective multicenter cohorts from Europe and Canada: Cardiovascular Comorbidity in Children with CKD (4C) and Haemodiafiltration, Heart and Height (3H) studies, conducted from 2009-19 and 2013-16, respectively. CV damage and risk factors were evaluated (i) cross sectionally at KRT-start (n = 248), and (ii) longitudinally over the 2-years preceding KRT start (n = 157; 331 patient-visits). Longitudinal analyses with mixed-effects models estimated associations of modifiable CV risk factors with change in carotid intima-media thickness (cIMT) standard deviation score (SDS), pulse wave velocity (PWV-SDS), left ventricular (LV) mass and systolic dysfunction. Findings: 248 patients, age 14.3 (12.2, 16.2) years were evaluated at median 35 (28-114) days before KRT start. Elevated cIMT-SDS and PWV-SDS were present in 43% and 25%, and LV hypertrophy and systolic dysfunction in 49% and 33%. Aortic stiffness and LV hypertrophy significantly increased, especially in the year before KRT start (adjusted odds ratio, OR 0.33, P = 0.002 and OR 0.54, P = 0.01, respectively). 79% of children had >3 modifiable CV risk factors at KRT onset. Diastolic BP and BMI were strongly associated with a linear increase in all CV measures. After controlling for CV risk factors, the time to KRT onset no longer predicted the burden of CV damage. Interpretation: This comprehensive CV evaluation shows the progressive accrual of modifiable risk factors and a high burden of CV damage in the years preceding KRT onset. CV damage in the pre-KRT period is preventable. Funding: Supported by EU4Health Programme (101085068) and Kidney Research UK (RP39/2013).

Effect of low-dose terazosin on arterial stiffness improvement: A pilot study.

Arterial stiffness, a prominent hallmark of ageing arteries, is a predictor of all-cause mortality. Strategies for promoting healthy vascular ageing are encouraged. Here we conducted a pilot study to evaluate the potential effects of low-dose Terazosin on arterial stiffness. We enrolled patients aged over 40 with elevated arterial stiffness, defined as a brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, who were administered Terazosin (0.5 and 1.0 mg/day) from December 2020 to June 2023. Treatment responses were assessed every 3 months. Linear regression analysis was used to characterise the improvement. We matched cases who took Terazosin for 1 year with Terazosin-free controls using propensity score matching (PSM). Our findings demonstrate that Terazosin administration significantly affected arterial stiffness. (1) Arterial stiffness significantly improved (at least a 5% reduction in baPWV) in 50.0% of patients at 3 months, 48.6% at 6 months, 59.3% at 9 months, and 54.4% at 12 months, respectively. (2) Those with higher baseline baPWV and hypertension exhibited a significantly reduced risk of non-response. (3) Terazosin was associated with a reduction of baPWV at 1-year follow-up (linear regression: ß = -165.16, p < 0.001). This pilot study offers valuable insights into the potential significance of Terazosin in improving arterial stiffness and paves the way for future randomised clinical trials in combating vascular ageing.

Epidural pressure measurement using a fiber-optic sensor (proof-of-principle in vivo animal trial).

BACKGROUND: An increase in epidural pressure around the stenosis has been observed in patients with lumbar spinal stenosis (LSS) with positive signs of sedimentation or redundant nerve roots. Further analysis of the pressure conditions in the stenotic area would be of great interest. We hypothesized that it would be possible to determine the physiological parameters of the epidural pulse wave and its course in pathological stenosis as a basis for objective identification of LSS based on pressure using a new measuring method with continuous spatial and temporal resolution. METHODS: We performed a single-case proof-of-principle in vivo animal trial and used a newly developed hybrid pressure-measurement probe with a fiber-tip Fabry-Pérot interferometer and several fiber Bragg gratings (FBG). RESULTS: With reproducible precision, we determined the mean epidural pressure to be 7.5 mmHg and the peak-to-peak value to be 4-5 mmHg. When analyzing the pressure measured by an FBG array, both the heart and respiratory rates can be precisely determined. This study was the first to measure the pulse wave velocity of the cerebrospinal fluid pressure wave as 0.97 m/s using the newly developed pressure probe. A simulated LSS was detected in real time and located exactly. CONCLUSIONS: The developed fiber-optic pressure sensor probe enables a new objective measurement of epidural pressure. We confirmed our hypothesis that physiological parameters of the epidural pulse wave can be determined and that it is possible to identify an LSS.

Estimated Pulse-Wave Velocity and Magnetic Resonance Imaging Markers of Cerebral Small-Vessel Disease in the NOMAS.

BACKGROUND: Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging. METHODS AND RESULTS: We included 1257 participants from the NOMAS (Northern Manhattan Study). The ePWV values were calculated using a nonlinear function of age and mean arterial blood pressure. The association between ePWV and white matter hyperintensity volume was assessed. Modification by race and ethnicity was evaluated. Associations between ePWV and other cerebral small-vessel disease markers, covert brain infarcts, cerebral microbleeds, and enlarged perivascular spaces, were explored as secondary outcomes. Mean±SD age of the cohort was 64±8 years; 61% were women; 18% self-identified as non-Hispanic Black, 67% as Hispanic, and 15% as non-Hispanic White individuals. Mean±SD ePWV was 11±2 m/s in the total NOMAS population and was similar across race and ethnic groups. The ePWV was significantly associated with white matter hyperintensity volume (ß=0.23 [95% CI, 0.20-0.26]) after adjustment. Race and ethnicity modified the association between ePWV and white matter hyperintensity volume, with stronger associations in Hispanic and non-Hispanic Black individuals. Significant associations were found between ePWV and covert brain infarcts, cerebral microbleeds, and perivascular spaces after adjustment. CONCLUSIONS: The ePWV function may provide a vascular mechanism for deleterious cerebrovascular outcomes in individuals with cerebral small-vessel disease and is particularly apparent in the racial and ethnic minorities represented in the NOMAS cohort.

The Role of Serum Erythropoietin (EPO) and Vascular Endothelial Growth Factor (VEGF) in Pulse Wave Velocity (PWV) Among Hypertensive Patients: A Cross-Sectional Study.

Background and objective While hypertension (HTN) is a major health-related threat globally, it is often an under-reported clinical condition as most of the stage I hypertensive patients do not present with any symptoms. The relationship between endogenous oxygen-sensing protein [erythropoietin (EPO) and vascular endothelial growth factor (VEGF)] levels and vascular stress in hypertensive patients is not fully understood as the mechanistic pathway by which these oxygen-sensing proteins alter the vascular physiology and cause hypertension is still a matter of debate. In light of this, we explored the role of these two proteins in the development of vascular stress including increased pulse wave velocity (PWV). We aimed to examine the correlation between oxygen-sensing proteins and vascular stress markers including PWV in hypertensive patients. Materials and methods We conducted a cross-sectional study involving age-matched participants classified into three groups (group 1: normotensive persons, n=36; group 2: stage I hypertensive patients, n=36; and group 3, stage II hypertensive patients, n=36). Adiposity-related parameters such as waist circumference (WC), hip circumference (HC), BMI, and waist-hip ratio (WHR) were measured. BP was recorded manually in resting posture by using a sphygmomanometer. PWV, which predicts the progression of BP and the development of HTN, was recorded using a periscope, which works based on the oscillometric method. Vascular stress-induced oxidative stress parameters [serum malondialdehyde (MDA) and serum nitric oxide (NO)] were also estimated by using a UV spectrophotometer. Quantitative estimations of oxygen-sensing proteins (serum EPO and serum VEGF) were done by using the ELISA kit method. The results were expressed as mean ± standard deviation (SD). The correlation between the variables was done using Spearman's correlation. A p-value <0.05 was considered statistically significant. Results Adiposity indices and vascular stiffness parameters were found to be significantly (p <0.05) increased in group 2 and group 3 compared to group 1. The levels of serum MDA were found to be significantly (p<0.05) increased in group 2 and group 3 than group 1, whereas the levels of serum NO were significantly (p<0.05) decreased in group 3 and group 2 than group 1. A significant (p<0.05) positive correlation was observed between the PWV and EPO (r=0.492) while a significant (p<0.05) negative correlation was observed between PWV and VEGF (r=-0.406) among the study population. Conclusion The results are indicative of the influence of vascular stress in stage I and II hypertensive patients. Furthermore, the relationship between oxygen-sensing proteins and vascular stress in hypertensive patients has also been established.

Serum myostatin is associated with central-to-peripheral arterial stiffness gradient in healthy adolescents. The MACISTE Study.

BACKGROUND: myostatin is a protein compound structurally related to the TGF-beta protein, which plays a pivotal role in regulating muscle growth and extracellular matrix production. exerts both profibrotic and antihypertrophic effects on vascular smooth muscle cells. Aim of the study was to explore the potential association between serum myostatin levels (sMSTN) and carotid-femoral pulse-wave velocity (cf-PWV), carotid-radial pulse wave velocity (cr-PWV), and their ratio (PWVr), in a cohort of healthy adolescents. METHODS: a cohort of 128 healthy subjects (mean age 17±2 years, 59% male) was randomly selected from participants to the MACISTE (Metabolic And Cardiovascular Investigation at School, TErni) study. sMSTN was assessed utilizing an enzyme-linked immunosorbent assay. PWVs were measured in the supine position using high-fidelity applanation tonometry. RESULTS: The mean cf-PWV was 5.1±0.9 m/s, cr-PWV was 6.9±0.9 m/s, PWVr was 0.75±0.12. PWVr exhibited a linear increase across increasing quartiles of sMSTN (0.71±0.1, 0.74±0.1, 0.7±0.1, 0.77±0.1, p for trend=0.03), whereas the association between sMSTN and each single component of PWVr (cf-PWV, cr-PWV) did not attain statistical significance. Quartiles of sMSTN displayed a positive trend with serum HDL-cholesterol (p=0.01) and a negative one with LDL-cholesterol (p=0.01). In a multivariate linear model, the association between PWVr and sMSTN was independent from SBP values, age, sex, heart rate, BMI, HDL-cholesterol and HOMA Index. CONCLUSIONS: In healthy adolescents, sMSTN showed independent associations with PWVr, a measure of central-to-peripheral arterial stiffness gradient. sMSTN may exert differential effects on the structural and functional properties of the arterial wall.

Effects of Acute Beetroot Juice Supplementation and Exercise on Cardiovascular Function in Healthy Men in Preliminary Study: A Randomized, Double-Blinded, Placebo-Controlled, and Crossover Trial.

Nitrate-rich beetroot juice (NRBRJ) can potentially enhance exercise performance and improve cardiovascular function, leading to an increased use of NRBRJ over the years. However, the combined effects of NRBRJ supplementation and exercise on cardiovascular function remain unclear. Therefore, this study compared cardiovascular function responses to submaximal exercise with either placebo (PLA) or NRBRJ supplementation in healthy men. Twelve healthy men (aged 25.2 ± 2.3 years) completed the 30-min submaximal cycle ergometer exercise trials corresponding to 70% maximal heart rate (HRmax) with either PLA or NRBRJ supplementation in a random order. The mean exercise load, heart rate (HR), stroke volume (SV), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during exercise. The brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) were measured before and after exercise. NRBRJ supplementation was more effective than PLA in increasing the mean exercise load and decreasing DBP and MAP during submaximal exercise. Furthermore, baPWV decreased in the NRBRJ trial and was considerably lower after exercise in the NRBRJ-supplemented group than in the PLA-supplemented group. FMD significantly increased in the PLA and NRBRJ trials; however, NRBRJ supplementation demonstrated a significantly higher FMD before and after exercise than PLA supplementation. In conclusion, acute NRBRJ supplementation and exercise were more effective than PLA supplementation and exercise in improving aerobic exercise capacity and cardiovascular function in healthy men.

Exploring the Association between Mediterranean Diet Adherence and Arterial Stiffness in Healthy Adults: Findings from the EvasCu Study.

(1) Background: Previous evidence has indicated a connection between a Mediterranean diet and cardiovascular disease. However, evidence for subclinical markers of cardiovascular disease, such as arterial stiffness, is limited. Therefore, the aim of this study was to assess the associations between adherence to the Mediterranean diet (MD), as assessed by the MEDAS-14 questionnaire, and arterial stiffness, as assessed by aortic pulse wave velocity, in healthy adults and according to sex. (2) A cross-sectional study including 386 healthy participants was performed in the EVasCu study. Adjusted and unadjusted differences in adherence to the MD and arterial stiffness were determined using Student's t test and ANCOVA for the total sample and according to sex. (3) Results: Our results showed that individuals with a high adherence to the MD had a greater arterial stiffness, both in the total sample and in females, although this difference was not significant after adjusting for possible confounding variables, such as age. (4) Conclusions: Our findings indicated that, in the unadjusted analyses, healthy subjects with a high adherence to the MD showed a greater arterial stiffness. When these analyses were adjusted, no significant differences were shown in a-PWv according to the categories of MD adherence.

The effect of time-restricted eating on arterial stiffness indices in men with metabolic syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Time-restricted eating (TRE) has been shown to be associated with improvements in some aspects of the metabolic syndrome. Nevertheless, only a few studies have addressed the effect of TRE on pulse wave velocity (PWV). We thus propose a randomized controlled trial to compare the effects of TRE with standard dietary advice on PWV and thereby present the protocol. METHODS: Forty-eight participants will be assigned to either TRE or control groups using simple randomization. The TRE group will consume their meals during a 10-h period and experience 14 h of fasting. They will also be advised to consume their last meal no later than 20:00. Both groups will receive standard dietary advice. The participants will be followed for 6 weeks. The primary outcome will be changes in PWV. Laboratory measurements, including lipid profile, liver enzyme tests, fasting blood glucose (FBG), insulin concentrations, and insulin resistance, as well as anthropometric data, blood pressure, basal metabolic rate, appetite status, physical activity level, sleep quality, cognitive function, quality of life, and calorie intake, will be evaluated throughout the study. DISCUSSION: The outcomes of this study will allow a comparison of the effects of TRE and standard dietary recommendations on PWV and other cardiometabolic factors in individuals with metabolic syndrome (MetS). TRIAL REGISTRATION: Iranian Registry of Clinical Trials; code: IRCT20201230049889N1; registered on August 14, 2022. The registration of the trial is accessible at: https://www.IRCT.ir/trial/64485?revision=281341 .

The role of non-invasive oscillometric method to detect aortic stiffness in patients with subclinical hypothyroidism.

INTRODUCTION: Subclinical hypothyroidism (SCH) is a biochemical condition that is diagnosed when peripheral free thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. The aim of this study was to investigate the relationship between SCH and arterial stiffness using two different non-invasive methods, including echocardiography and oscillometric arteriography. MATERIAL AND METHODS: The study included 33 newly diagnosed SCH patients and 34 age- and gender-matched healthy controls. Systolic and diastolic diameters and elastic parameters of the aorta were calculated by 2D Transthoracic echocardiography (TTE). Central blood pressure and aortic stiffness values of patient groups were measured noninvasively from the brachial artery using Mobil-O-Graph arteriography. Pulse wave velocity (PWV) and augmentation index (AIx) were used as arterial stiffness indicators. RESULTS: There was no significant difference between SCH and control groups with regard to age, gender, and body mass index (BMI). Aortic strain and aortic distensibility, were significantly lower in the SCH group than in the control group (p < 0.001). PWV and AIx which measured by Mobil-O-Graph arteriography were found to be significantly higher in the subclinical hypothyroid group compared to the control group (p < 0.05). CONCLUSION: Aortic stiffness assessed by TTE and Mobil-O-Graph arteriography deteriorated in patients with SCH after excluding other cardiovascular risk factors. The assessment of aortic stiffness by the oscillometric method was easy and useful for widespread clinical use.

No association between vascular aging and sarcopenia in healthy participants.

BACKGROUND & AIMS: Several reports inform an association between vascular aging and sarcopenia. However, both conditions appear along with aging. Therefore, their association may be circumstantial and not casually linked. Our aim was to determine if individuals with higher-than-expected vascular aging have a higher frequency of sarcopenia. METHODS: In 802 participants we calculated the association between pulse wave pressure and carotid intima media thickness and age and blood pressure, to derive predictive regression equations. In 161 of these participants we measured body composition by double beam X ray absorptiometry (DEXA), hand grip strength, rectus femoris thickness by ultrasound, activity energy expenditure by actigraphy and peak oxygen consumption and workload in an incremental exercise test. We calculated their expected values for pulse wave velocity and carotid intima media thickness and compared muscle mass and function between those with higher or lower than expected parameters. In 60 of these participants, we measured body composition sequentially to assess its change over time. RESULTS: Age and blood pressure predicted the variance of pulse wave velocity and carotid intima media thickness with R2 values of 0.94-0.97 and 0.54 to 0.66, respectively. No differences in the frequency of sarcopenia and in muscle mass and strength were observed between participants with higher or lower than expected pulse wave velocity and carotid intima media thickness. In the group with sequential assessments, no differences in the change of muscle mass over time were observed in participants with and without accelerated vascular aging. CONCLUSIONS: We were not able to find an association between vascular aging and sarcopenia.

Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Background: Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. Methods: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. Discussion: It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching.

PURPOSE: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. METHODS: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. RESULTS: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). CONCLUSION: PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Effects of metformin on arterial elasticity and pro-inflammatory markers in black diabetes patients.

Background: Pro-inflammatory markers are linked with the development and progression of type 2 diabetes mellitus and arterial stiffening. Pulse Wave Velocity (PWV) and Augmentation Index (Aix) are non-invasive standard markers of arterial elasticity and predictors of cardiovascular mortality and morbidity. Aim: To investigate the effects of metformin alone and in combination with glimepiride on arterial elasticity, pro-inflammatory cytokines in black type 2 diabetes mellitus patients. Settings: Participants were enrolled from Sefako Makgatho Health Sciences University community, Gauteng, South Africa. Methods: PWV and Aix were measured using the AtCor SphygmoCor® system (AtCor Medical, Inc., Sydney, Australia). Cytokines levels were measured using Multiplexing with Bio-Plex Pro™ human inflammation panel I assay. Treatment naïve type 2 diabetes participants were divided into two groups: metformin (M) (n = 10) and metformin glimepiride (MS) (n = 14). The study participants were followed up at 4 and 8 months after treatment initiation. Results: In the M and MS, IL-1ß increased significantly at four months (58.19 ± 0.03 pg/ml, 58.35 ± 0.30 pg/ml) when compared to baseline (33.05 ± 18.56 pg/ml, 34.79 ± 18.77 pg/ml) then decreased significantly at eight months (29.25 ± 11.64 pg/ml, 32.54 ± 14.26 pg/ml) when compared to four months (58.19 ± 0.03 pg/ml, 58.35 ± 0.3 pg/ml) (p < 0.05). There were no significant changes in PWV, Aix, IL-1ra, IL-2, IL-6, IL-8, TNF-α and hs-CRP levels at both treatment intervals. Conclusion: Metformin alone or in combination with glimepiride did not improve arterial elasticity and did not reduce pro-inflammatory cytokines levels in T2DM black South African patients. Contribution: The context-based knowledge generated by the current study is expected to enhance the continuum of care for T2DM patients.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma.

PURPOSE: To identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study. METHODS: A total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of cirrus OCT. RESULTS: Thirty-two eyes displayed choroidal MvD (62.7 (95% CI 58.4-67.0) years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV≥1400cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P=0.023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P=0.025). CONCLUSIONS: In NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Estimated Pulse Wave Velocity is Associated with a Higher Risk of Dementia in the Health and Retirement Study.

BACKGROUND: In this paper, we use the Health and Retirement Study (HRS) to examine the relationship between an estimated measure of pulse wave velocity (ePWV) and cognitive impairment with no dementia and dementia, respectively. METHODS: We modeled the relationship between ePWV and cognitive status in 2006/2008 using data from 8,492 men and women (mean age 68.6 years) controlling for age, blood pressure, sociodemographic and socioeconomic characteristics (sex, race and ethnicity, education, income, wealth), health behaviors (smoking and physical activity), body mass index (BMI), health status and related medication use (history of cardiovascular disease, diabetes, and stroke), and cerebrovascular disease (CVD)-related biomarkers (C-reactive protein, cystatin-C, hemoglobin A1c, total cholesterol, high-density lipoprotein [HDL] cholesterol). We assess cognitive function with the 27-item Langa-Weir Telephone Interview for Cognitive Status (TICS) scale. ePWV is derived from an equation based on participant age and resting blood pressure. RESULTS: In a model that controlled for the constituent components of ePWV (age, age squared, systolic and diastolic blood pressure), ePWV is associated with increased odds of having cognitive impairment with no dementia (OR=2.761) and dementia (OR=6.344) relative to a group with no cognitive impairment or dementia. After controlling for the constituent components of ePWV, sociodemographic and socioeconomic characteristics, health status and medication use, health behaviors, BMI, and CVD-related biomarkers, ePWV remains significantly associated with dementia (OR=3.969) but not cognitive impairment with no dementia (OR=1.782). CONCLUSIONS: These findings suggest that ePWV may be a novel research tool and biomarker of vascular aging that can be used in large, population-representative studies to examine cognitive aging and dementia risk.

Effect of adding PCSK9 inhibitors to lipid-lowering interventions on arterial stiffness: A systematic review and meta-analysis.

BACKGROUND: Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction. METHODS: A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness. RESULTS: Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: -2.61 m/s [95% CI: -3.70, -1.52]; ES: -1.62 [95% CI: -2.53, -.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics. CONCLUSION: The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction.

Fontan Circulation and Aortic Stiffness: Insights into Vascular Dynamics and Haemodynamic Interplay.

Increased aortic stiffness predisposes cardiac afterload and influences cardiac function. Congenital heart diseases involving aortic arch malformation and extended cardiovascular surgery, i.e. univentricular heart diseases, can lead to increased aortic stiffness. This study aimed to investigate whether Fontan patients (FO) have increased aortic stiffness within distinct aortic segments, and whether these parameters relate to Fontan-specific haemodynamics. In a prospective case-control study, 20 FO and 49 heart-transplanted control subjects with biventricular circulation underwent invasive cardiac catheterisation. We invasively measured pulse wave velocity (PWV) in the ascending aorta and along the entire aorta. Haemodynamic parameters, including end-diastolic pressure, pulmonary artery pressure, the cardiac index and systemic vascular resistance index were also assessed. FO exhibited significantly higher ascending aorta PWV (aPWV) than controls (FO: 7.2 ± 2.4 m/s|Controls: 4.9 ± 0.7 m/s, p < 0.001) and compared to the inner group central aorta PWV (cPWV; FO: 5.5 ± 1.2 m/s|Controls: 5.3 ± 1.0 m/s). Multivariate analysis confirmed this aPWV elevation in FO even after adjusting for age and BMI. aPWV and cPWV were almost identical within the control group. Correlation analyses revealed associations between cPWV and blood pressure in controls, while correlations were less apparent in FO. We detected no significant association between the aPWV and other haemodynamic parameters in any of our groups. FO exhibit increased aPWV, indicating specific vascular stiffness in the ascending aorta, while their overall aortic stiffness remains comparable to controls. Further research is needed to understand the implications of these findings on Fontan circulation and long-term cardiovascular health. CENTRAL MESSAGE: Fontan patients show increased aortic arch pulse wave velocity, suggesting specific vascular stiffness. PERSPECTIVE STATEMENT: Our study offers rare insights into pulse wave velocity in Fontan patients, highlighting increased arterial stiffness in the aortic arch. Vascular stiffness was particularly increased in the area of surgical reconstruction. This indicates the need for further research on vascular stiffness in Fontan circulation to understand its impact on cardiovascular health. CLINICAL TRIAL REGISTRATION: German clinical trial registration, DRKS00015066.

Are aortic biomechanical properties early markers of dilatation in patients with Marfan syndrome? A systematic review and meta-analysis.

Although tissue stiffness is known to play an important role in aortic dilatation, the current guidelines for offering preventative surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in vivo aortic stiffness measures in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation. Following the PRISMA guidelines, we collected literature on diameter and three in vivo stiffness measures: Pulse wave velocity (PWV), ß -stiffness index (SI) and distensibility, at five different aortic locations in patients with Marfan syndrome. Results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining data from the literature. Regression with respect to age and statistical comparisons were performed. Thirty articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be higher in Marfan, but only in dilated aortas. Distensibility was found to be lower even in non-dilated aortas, and its decrease was associated with higher chances of developing aortic dilatation. ß -SI was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis, all stiffness measures showed a significant variation with age. Distensibility and ß -stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation. From the literature, ß -SI and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further investigation of criteria combining stiffness and diameter is recommended to better assist clinical decisions for prophylactic surgery.

The Value of Serial Measurement of Arterial Stiffness in Cardiovascular Disease.

Clinically assessing arterial stiffness is valuable because it aids in predicting future cardiovascular events. There are several methods for measuring arterial stiffness, including pulse wave velocity (PWV), augmentation index, and pulse pressure. Numerous studies have shown that these indicators of arterial stiffness possess prognostic value for various patient groups as well as the general population. In cross-sectional studies, arterial stiffness was also linked to organ damage indices. However, most studies related to arterial stiffness have relied on a single measurement. Taking multiple serial measurements of arterial stiffness offers several advantages. Through repeated assessments, one can confirm the variability of arterial stiffness and observe changes over time, which is beneficial for understanding its pathophysiology. Such repeated measurements are also invaluable in evaluating the efficacy of interventions aimed at improving arterial stiffness. However, caution is needed, as there is no standardized method for measuring arterial stiffness. For instance, with PWV, the values can be influenced by numerous external factors. Therefore, the external conditions during the measurement must be noted. It's essential to recognize the pros and cons of repeated arterial stiffness measurements and integrate them effectively into clinical practice.