Search Results (142)

Objective: Evaluate the efficacy and safety following intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular oedema (DME). Methods: To evaluate retinal microvascular remodelling and photoreceptor metrics using adaptive optics (AO) alongside systemic vascular status assessed by brachial/aortic hemodynamic and carotid ultrasound. We conducted a single-centre longitudinal study including twenty-one patients with DME. The following four diagnostic visits were performed: baseline (V1, no anti-VEGF treatment), 2–3 months (V2), 6–8 months (V3), and 12–14 months (V4). Adaptive optics (rtx1) measured foveal cone number (N) and regularity (Reg) within a standardised 80 × 80 µm window, and superior temporal retinal arteriole morphology after the first bifurcation (vessel diameter [VD], lumen diameter [LD], wall thickness [WT], wall-to-lumen ratio [WLR], and wall cross-sectional area [WCSA]). SphygmoCor provided peripheral (brachial) and central (aortic) pressures, augmentation pressure (AP), augmentation index (AIx), and carotid–femoral pulse wave velocity (PWV and PWVHR heart rate adjusted). Carotid ultrasound assessed intima–media thickness (IMT), carotid lumen diameter (CLD), and IMT/CLD ratio (IMTLR) 2 mm proximal to the bifurcation in diastole. Visual acuity (Visus), intraocular pressure (IOP), and central retinal thickness (CRT) were obtained at each visit. Results: In the treated eye (TE), WLR showed a significant overall change (Friedman p = 0.007), with a modest V4 vs. V1 increase (Wilcoxon p = 0.045); LD also varied across visits (Friedman p = 0.034). Cone metrics improved as follows: Reg increased over time (Friedman p = 0.019), with a significant rise at V4 vs. V1 (p = 0.018), and cone number increased at V3 vs. V1 (p = 0.012). Functional/structural outcomes improved as follows: visual acuity increased at V3 (p = 0.009) and V4 (p = 0.028), while CRT decreased at V3 (p = 0.002) and V4 (p = 0.030); IOP remained stable compared to V1. Systemic hemodynamics was largely unchanged; small fluctuations in DBP and cDBP across V1–V4 were observed (Friedman p = 0.034 and p = 0.022, respectively), whereas AIx, AP, PWV, and PWVHR showed no significant trends. Carotid IMT, CLD, and IMTLR did not change significantly across visits, supporting systemic vascular safety. Conclusions: Intravitreal anti-VEGF therapy in DME was associated with improvements in photoreceptor organisation and macular structure/function, with AO-derived arteriolar remodelling detectable over time, and no adverse changes in large-artery structure. These findings support ocular efficacy and systemic vascular safety; confirmation in larger cohorts is warranted. Full article

Cardiovascular disease (CVD) remains the leading cause of death worldwide, accounting for nearly one-third of global mortality. Arterial stiffening, particularly in the central elastic arteries, impairs the Windkessel (cushioning and pumping) function and contributes to cardiovascular risk beyond traditional factors. Carotid–femoral pulse wave velocity (cfPWV) is established as the gold standard for assessing aortic stiffness and predicting cardiovascular and all-cause mortality; however, its technical complexity and requirement for trained personnel limit its use in routine clinical and community settings. These challenges have driven the development of simplified techniques for population screening, such as brachial–ankle PWV (baPWV). More recently, single-cuff oscillometric devices have emerged as practical alternatives. These methods are simple enough to be implemented in daily healthcare at home, thereby greatly enhancing accessibility, although their accuracy depends on model assumptions and calibration. In this perspective article, we highlight the pathophysiological significance of preserving the central arterial Windkessel function and emphasize the need for its practical assessment. Recent innovations mark a paradigm shift from complex laboratory-based measurements toward simplified, data-driven, and socially feasible screening tools for the early detection and prevention of CVD. Full article

Background/Objectives: Phenylacetylglutamine (PAG), a gut microbiota-derived metabolite, may contribute to the development of cardiometabolic diseases. The diagnostic value of PAG for vascular dysfunction in hemodialysis (HD) remains unclear. This study assessed how serum PAG levels relate to carotid–femoral pulse wave velocity (cfPWV), which is a validated index of aortic stiffness, in patients on maintenance HD. Methods: A total of 138 patients on maintenance HD were enrolled. Participants with cfPWV values greater than 10 m/s were categorized as having aortic stiffness. Serum PAG levels were measured using high-performance liquid chromatography–mass spectrometry. Results: Aortic stiffness was present in 33.3% of patients. Those with aortic stiffness were older (p = 0.016), had a higher prevalence of diabetes mellitus (p = 0.030) and hypertension (p < 0.001), and had higher systolic (p < 0.001) and diastolic (p < 0.001) blood pressures, glucose (p = 0.005), and serum PAG (p < 0.001) levels. Multivariable analysis identified serum PAG (odds ratio [OR] = 1.903; 95% confidence interval [CI] = 1.171–3.094, p = 0.009) and age (OR = 1.042, 95% CI = 1.001–1.084, p = 0.044) as independent determinants of aortic stiffness. Linear regression revealed that PAG (p < 0.001), systolic blood pressure (p < 0.001), age (p = 0.013), and glucose level (p = 0.024) were positively associated with cfPWV. Conclusions: Among individuals undergoing maintenance HD, higher serum PAG levels independently predicted greater aortic stiffness. PAG may be a potential diagnostic biomarker for vascular stiffness and a tool for cardiovascular risk stratification in this population. Full article

Background: Arterial stiffness assessed by measuring pulse wave velocity (PWV) is a well-established predictor of cardiovascular mortality. To our knowledge, no studies on arterial stiffness in kidney transplant recipients (KTRs) from Tunisia have been conducted. The present study aimed to assess arterial stiffness in Tunisian KTRs and to identify the key predictors associated with its increase. Methods: We conducted a cross-sectional, single-center study enrolling Tunisian KTRs aged 18 years or older with a minimum post-transplant follow-up of six months. Arterial stiffness was measured as pulse carotid–femoral PWV (CF-PWV) by a Complior device. A CF-PWV ≥ 10 m/s was defined as elevated. Results: Fifty-four KTRs were included (mean age: 42.55 ± 10.61 years). Among them, 19 (35.2%) had a CF-PWV ≥ 10 m/s. The univariate analysis showed a significant association between elevated CF-PWV and the following parameters: age, hypertension prior to transplantation, dyslipidemia, donor age, parameters obtained through office blood pressure measurement (systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP)), central SBP recorded by the Complior device, nocturnal SBP obtained through 24 h ambulatory blood pressure monitoring (ABPM), and fasting blood glucose. A multivariable analysis with CF-PWV ≥ 10 m/s as a dependent variable retained the following independent factors: dyslipidemia (p = 0.015; OR = 60.32), donor age (p = 0.014; OR = 1.16), SBP obtained through office blood pressure measurement (p = 0.015; OR = 1.25), and fasting blood glucose (p = 0.034; OR = 22.35). Conclusions: Given the major impact of cardiovascular disease on post-transplant outcomes, understanding the determinants of arterial stiffness is crucial for improving patient care. Routine PWV assessment may not be feasible in all centers due to cost or limited equipment availability. Therefore, identifying the clinical and biological markers associated with arterial stiffness offers a low-cost and widely accessible alternative for evaluating cardiovascular risk. These findings may support the development of a simple risk score to help nephrologists detect and manage high-risk KTRs more effectively. Full article

Pulse wave velocity (PWV) is a useful biomarker in the monitoring and risk stratification of various cardiovascular diseases including hypertension. The current gold standard for non-invasive measurement is carotid-femoral PWV (cfPWV) measurement via direct tonometry. However, cfPWV provides only a global PWV measure, which emphasises the need for an alternative capable of local PWV assessment. There are several alternatives for local PWV measurement proposed in the literature and one promising alternative is ultrasound, which offers good penetration depth, accessibility, and a relatively low cost, making it well-suited for non-invasive, real-time acquisition of haemodynamic parameters for PWV estimation. This paper aims to evaluate the different approaches for ultrasound-based acquisition while considering technical and physiological constraints to optimise the accuracy, reliability, and reproducibility of the parameters collected for estimation. In particular, this paper focuses on the flow-area (QA) and lnDiameter-velocity (lnDU) methods, which require local area and velocity data for PWV estimation. Accordingly, this paper discusses the use of ultrasound imaging in vessel data acquisition, highlights various challenges and considerations to be managed during acquisition and processing, outlines the different ultrasound-based imaging modalities for acquiring area and velocity data, and compares the simultaneous and non-simultaneous acquisition of data for PWV estimation. Full article

Background/Objectives: Ischemic cardiomyopathy is a major cause of morbidity and mortality. Obesity is paradoxically associated with better outcomes, while clustering of cardiometabolic risk factors (CMRFs)—diabetes mellitus, arterial hypertension, and hyperlipidemia—is associated with worse prognosis in heart failure (HF) patients. The interplay between vascular function, obesity and clustering of CMRFs in ischemic HF is not thoroughly investigated. Methods: In a prospective, single-center cohort study, 560 patients with ischemic cardiomyopathy were followed for a median of 43 months. Baseline BMI, CMRFs and markers of vascular function including flow-mediated dilation (FMD), and carotid–femoral pulse wave velocity (cf-PWV) were assessed. Major adverse cardiovascular events (MACE), including death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure or other cardiovascular causes, were recorded. Cox proportional hazards models and cubic spline analyses evaluated associations and nonlinear relationships. Results: Obesity was independently associated with a 50% lower risk of MACE (HR 0.50; 95% CI 0.32–0.981; p = 0.01) and improvement of FMD by 1% corresponded to a 7% reduction in MACE risk (HR 0.93; 95% CI 0.87–0.99; p = 0.03) after adjusting for multiple confounders. Clustering of all three CMRFs predicted greater MACE risk (HR 1.42; 95% CI 1.03–1.95; p = 0.03). No significant differences in FMD or cf-PWV were observed across BMI groups. cf-PWV values were impaired among patients with all 3 CMRFs but cf-PWV did not predict MACE. Conclusions: Higher BMI and FMD each independently predict improved outcomes in ischemic cardiomyopathy. The clustering of cardiometabolic risk factors is a strong predictor of adverse events. Full article

Introduction: Long COVID (LC) is associated with an increase in cardiovascular risk and chronic inflammation, whereas the Mediterranean Diet (MD) seems to improve the aforementioned factors. The aim of this study is to analyse the relationship between MD and its components with vascular structure, function, and aging in patients diagnosed with LC globally and by sex. Methods: This study was a cross-sectional study with 304 subjects diagnosed with LC; 207 were women and 97 men. Adherence to MD was evaluated with a validated MEDAS questionnaire, composed of 14 items. The vascular structure was assessed using carotid intima-media thickness (cIMT). Three measurements were carried out to evaluate vascular function: cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), and carotid-femoral pulse wave velocity (cfPWV). Vascular aging index (VAI) was estimated. Results: The MD score was 7.80 ± 2.33, with no difference between sexes. Vascular function and aging parameter values were higher in men than in women. Use of olive oil as the principal source of fat for cooking, and consuming <1 serving of butter/day and <1 sugar-sweetened beverage/day showed >90% adherence. Logistic regression analysis displayed associations between cIMT < 0.625 and use of olive oil in the global analysis (OR = 0.148) and among men (OR = 0.120), and <2 commercial pastries/week in global (OR = 0.536). cfPWV < 7.400 m/s was associated with DM score ≥ 8 in global (OR = 0.444) and in women, as well as with <2 pastries/week in women (OR = 0.405). baPWV < 12.315 m/s was associated with ≥3 servings of pulses/week in global (OR = 0.481) and among women, as was <2 pastries/week in global (OR = 0.471) and in women. CAVI < 7.450 was associated with ≥4 tablespoons of olive oil/day in men. VAI < 63.693 was associated with DM score ≥ 8 in global (OR = 0.458) and in women, as well as <2 pastries/week in global (OR = 0.392). Conclusions: Adherence to MD was associated with lower cfPWV and VAI measures in the global analysis and among women. In particular, several of the components were associated with a better vascular profile in LC patients. Full article

Background and Aims: Placental growth factor (PlGF) is an important predictive marker of pregnancy complications such as preeclampsia. The aim of this study is to assess whether PlGF measured outside of pregnancy is a predictive marker for cardiovascular disease (CVD) risk in young women. Methods: This study was embedded in the Generation R Study, a population-based prospective cohort study. PlGF concentrations, as well as systolic and diastolic blood pressure (SBP and DBP), cardiac outcomes, carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibres of 5077 women, were assessed six years after pregnancy, which was considered baseline. Four years after baseline, we measured blood pressure and intimal media thickness (IMT). Eight years after baseline, we measured blood pressure and the post-occlusive reactive hyperaemia index (PORH index). In addition, we examined the influence of pregnancy complications on these associations. Results: We found a positive association between PlGF levels with SBP (0.46, 95% CI 0.04; 0.89). PlGF was not associated with retinal or echocardiographic measurements. PlGF was positively associated with DBP after four years and with both SBP and DBP eight years after baseline, independent of the occurrence of pregnancy complications. PlGF was not associated with IMT or the PORH index. Conclusions: PlGF is associated with higher blood pressure. PlGF may, therefore, be used as a marker of hypertension. These results need to be replicated in an independent cohort study. Full article

Background and Objectives: Indoxyl sulfate (IS), a gut microbiota-derived metabolite of tryptophan, is implicated in vascular dysfunction through oxidative stress and inflammation. This study evaluated the association between serum IS levels and aortic stiffness (AS) in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This cross-sectional study enrolled 80 patients with T2DM from a medical center in eastern Taiwan, excluding patients with malignancy, acute infection, heart failure, or recent cardiovascular events. Serum IS concentrations were quantified using liquid chromatography–mass spectrometry. AS was assessed using carotid–femoral pulse wave velocity (cfPWV), with values > 10 m/s indicating AS. Results: A total of 30 patients (37.5%) had AS. IS levels were significantly higher in the AS group than in the control group (p < 0.001). After multivariate adjustment, IS remained an independent predictor of AS (odds ratio: 2.565, 95% confidence interval: 1.145–5.748, p = 0.022). Linear regression analysis confirmed IS as an independent contributor to cfPWV values (β = 0.261, p = 0.019). Receiver operating characteristic analysis showed fair discriminatory ability (area under the curve = 0.739, p < 0.001). Conclusions: In patients with T2DM, serum IS is an independent predictor of AS and may serve as a promising nontraditional biomarker for cardiovascular risk stratification. Full article

Background: High-sensitivity cardiac troponin T serum concentration (hs-cTnT) measurement is a well-established tool in the diagnosis of acute cardiovascular (CV) disease. It remains unclear whether resting hs-cTnT could be useful for screening the status of the CV system. The purpose of this study was to compare the correlation between hs-cTnT, determined in patients without clinical symptoms of acute illness, and selected parameters of subclinical CV dysfunction in relation to the coexistence of arterial hypertension (AH). Methods: In total, 101 patients were included in the analysis. The following methods were used to assess the CV system: transthoracic echocardiography, Doppler ultrasonography of the carotid and lower extremity arteries with intima–media thickness (IMT) measurement, pulse wave velocity (PWV), central blood pressure measurement, ankle–brachial index (ABI), and toe–brachial index (TBI). Results: In patients with AH, significant correlations were found between hs-cTnT and maximal velocity of tricuspid regurgitation (R = 0.397; p = 0.003), left atrium volume index (LAVI) (R = 0.39; p = 0.002), and IMT in carotid arteries (cIMT) (R = 0.4; p = 0.001), common femoral arteries (cfIMT) (R = 0.384; p = 0.004), and superficial femoral arteries (sfIMT) (R = 0.352; p = 0.01), as well as PWV (R = 0.63; p < 0.001), central systolic blood pressure (cSBP) (R = 0.34; p = 0.006), central pulse pressure (cPP) (R = 0.354; p = 0.004), and ankle–brachial index (ABI) (R = −0.28; p = 0.024). In multivariate analysis, the relationship between subclinical CV dysfunction and hs-cTnT remained significant for LAVI, cSBP, cPP, and ABI, as well as showing borderline significance for sfIMT. In patients without AH, only the relationship between hs-cTnT and ABI was significant. According to interaction analysis, AH significantly influenced the relationship between hs-cTnT and cSBP, cPP, and sfIMT. Conclusions: Resting hs-cTnT correlates significantly with selected parameters of subclinical CV dysfunction in patients with AH. This relationship is clearly weaker in patients without AH. Further research is needed, especially prospective studies on a larger group of patients. Full article

Diabetes-related pathophysiological processes contribute to endothelial dysfunction, arterial stiffening (AS), hypertension, vascular remodeling, and impaired myocardial perfusion. This study aimed to assess the relationship between arterial wall parameters and sST2 concentration as potential risk factors in type 2 diabetes (T2DM) and investigate sex-related differences. To achieve this, we enrolled 100 patients with suspected or exacerbated coronary artery disease (CAD) and divided them into a T2DM group (n = 58) and a control group (n = 42). Endothelial reactivity (lnRHI), ABI, sST2 levels, and carotid–femoral (cfPWV) and carotid–radial pulse wave velocity (crPWV) were assessed. Coronary angiography was performed in every patient, and epicardial flow and myocardial perfusion were evaluated using QuBE and FLASH. Our results showed that the coronary angiographic findings were similar in both groups. However, T2DM patients had a significantly higher central AS (cfPWV 10.8 ± 2 vs. 9.9 ± 2.7 m/s, p < 0.05) and vascular age (70.0 ± 12.3 vs. 61.3 ± 15.4 years, p < 0.05), while peripheral AS, RHI, and ABI showed no differences. CfPWV correlated with renal function; higher HbA1c and sST2 levels were additionally associated with advanced vascular age. Notably, central AS and vascular age were higher in men with T2DM but not in women. These findings indicate that T2DM patients exhibit increased central AS and vascular aging, influenced by sST2 levels, suggesting fibrosis as a target for precision medicine in T2DM. Full article

p-Cresyl sulfate (PCS), a gut-derived uremic toxin with proinflammatory and cytotoxic effects, has been implicated in cardiovascular injuries among patients with chronic kidney disease (CKD). Aortic stiffness (AS), assessed by carotid–femoral pulse wave velocity (cfPWV), is a recognized predictor of cardiovascular risk. This study investigated the association between serum PCS levels and AS in patients with nondialysis-dependent CKD. In total, 165 patients with nondialysis-dependent CKD were enrolled. Clinical data and fasting blood samples were collected. Arterial stiffness (AS) was assessed bilaterally by measuring carotid–femoral pulse wave velocity (cfPWV) on both the left and right sides. A value above 10 m/s was considered indicative of increased stiffness. Serum PCS levels were quantified using high-performance liquid chromatography–mass spectrometry. Fifty patients (30.3%) had AS. The AS group was significantly older and had higher diabetes prevalence, systolic blood pressure, fasting glucose, urinary protein-creatinine ratio, and PCS levels than the control group. In the multivariate analysis, both PCS (odds ratio [OR]: 1.097; 95% confidence interval [CI]: 1.024–1.175; p = 0.008) and age (OR: 1.057; 95% CI: 1.025–1.090; p < 0.001) were independently associated with AS. In conclusion, elevated serum PCS and older age were independently associated with AS. Thus, PCS is a potential early marker of vascular damage in CKD. Full article

Objectives: We aimed to quantify the damage burden measured using the Damage Index for Antiphospholipid Syndrome (DIAPS) in patients with antiphospholipid syndrome (APS) and identify patients with high damage as well as any correlations of damage with subclinical atherosclerosis. Methods: Patient damage was assessed via DIAPS. Based on demographic, clinical and laboratory characteristics, patients were divided into two subgroups: thrombotic APS patients with high vs. low damage, and non-thrombotic aPL-positive patients with vs. without damage. Participants underwent carotid/femoral ultrasound for atherosclerotic plaque detection and carotid–femoral and carotid-radial pulse wave velocity (PWV). Results: We included 112 patients with an APS diagnosis, 57 (50.9%) with primary APS and 55 (49.1%) with associated SLE. Cardiovascular (CVD) risk factors and complications were significantly more frequent in the thrombotic group, as well as in patients with high damage within the thrombotic group. We did not identify any risk factors for increased damage in the non-thrombotic group. Atherosclerotic plaque presence was present in 27 (24%) of the patients in this study with the same frequency in the APS and APS/SLE groups (p = 0.5446). Pulse wave velocity (PWV) was elevated in 27–32% patients according to analyzed arteries. Elevated PWV was more frequent in the APS group in comparison to APS/SLE only between carotid and radial arteries (p = 0.0012). Both atherosclerotic plaque presence and PWV did not correlate with damage severity. Conclusions: DIAPS indicates substantial damage in APS patients in our study. High organ damage mainly affected thrombotic patients and was related to CVD complications. At the same time, screening of subclinical atherosclerosis seems not to predict higher damage in APS patients. Full article

Background: Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality, despite advances in treatment. Early detection of vascular aging is critical, as preclinical atherosclerosis often remains undiagnosed. AI-determined vascular age, originally developed using carotid-femoral pulse wave velocity (cf-PWV), may help to identify individuals at elevated risk. This study aimed to evaluate the clinical utility of an alternative AI-determined vascular age model based on the arterial velocity pulse index (AVI) and arterial pressure volume index (API) in a Japanese hospital-based cohort. Methods: This retrospective, exploratory study analyzed electronic health records of 408 patients from Yokohama City University Hospital. This study was approved by the Clinical Research Ethics Committee (approval numbers: B180300040, F240500007), and patient consent was obtained through an opt-out process. AI-determined vascular age was estimated using a Generalized Additive Model (GAM) with backward stepwise regression, substituting cf-PWV with AVI and API. Correlations with chronological age were assessed, and comparisons of cardiovascular and renal function markers were performed across age-stratified groups. Results: AI-determined vascular age showed a strong correlation with chronological age (p < 0.05). Significant differences were observed in cardiac diastolic function parameters, B-type natriuretic peptide (BNP), and estimated glomerular filtration rate (eGFR) between the highest and lowest quintiles of AI-determined vascular age. Conclusions: AI-determined vascular age using AVI and API appears to be a feasible surrogate for cf-PWV in clinical settings. This index may aid in stratifying vascular aging and identifying individuals who could benefit from early cardiovascular risk management. Full article

Cardiovascular adaptation is vital for a healthy pregnancy but may be impaired in women at high risk for preeclampsia (PE), a condition marked by endothelial dysfunction. Smoking may lower the PE risk but harms vessels, and the effects of early cessation remain unclear. This prospective cohort study assessed vascular changes in high-risk pregnancies and the potential influence of early smoking cessation. Of 110 women screened for PE in the first trimester, 43 were classified as high-risk: 18 former smokers and 25 lifelong non-smokers. Vascular assessments were performed at 11–16, 24–28, and 34–37 weeks of gestation. Parameters included the carotid–femoral pulse wave velocity (cfPWV), asymmetric dimethylarginine (ADMA), mean arterial pressure (MAP), systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and retinal vessel calibers (central retinal arteriolar and venular equivalents (CRAE, CRVE)). Serum cotinine confirmed abstinence in former smokers. Across gestation, ADMA (p = 0.034), MAP (p = 0.001), SBP (p = 0.033), DBP (p = 0.004), and HR (p = 0.004) increased, while CRAE (p = 0.016) and CRVE (p = 0.004) narrowed in late pregnancy; cfPWV remained stable (p = 0.783). Non-smokers showed increases in their ADMA (p = 0.020), MAP (p = 0.001), and DBP (p = 0.0001) with no differences between groups. High-risk pregnancies showed vascular changes with similar profiles in former and non-smokers, underscoring the need for broader studies. Full article