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.

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

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

Assessment of Early Vascular Aging Ambulatory Score (EVAAs): A Large Population-based External Validation Study.

BACKGROUND: Pulse Wave Velocity (PWV) remains the gold-standard method to assess Early Vascular Aging (EVA) defined by arterial stiffness. However, its high cost, time-consuming process, and need for qualified medical staff shows the importance of identifying alternative methods for the EVA evaluation. OBJECTIVE: In order to simplify the process of assessing patients' EVA, we recently developed the Early Vascular Aging Ambulatory score (EVAAs), a simple tool to predict the risk of EVA. The aim of the present study was the external validation of EVAAs in an independent population. METHODS: Eight hundred seventy-nine (46.3% men) patients who were referred to our Hypertension ESH Excellence Center were included in this study. The mean age was 46.43 ± 22.87 years. EVA was evaluated in two different ways. The first assessment included c-f PWV values, whereas the second one included EVAAs without the direct measurement of carotid-femoral PWV. RESULTS: The null hypothesis was that the prediction of EVA based on EVAAs does not present any statistically significant difference compared to the prediction based on the calculation from c-f PWV. Mean squared error (MSE) was used for the assessment of the null hypothesis, which was found to be 0.40. The results revealed that the EVAAs show the probability of EVA with 0.98 sensitivity and 0.75 specificity. The EVAAs present 95% positive predictive value and 92% negative predictive value. CONCLUSION: Our study revealed that EVAAs could be as reliable as the carotid-femoral PWV to identify patients with EVA. Hence, we hope that EVAAs will be a useful tool in clinical practice.

Effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women: a systematic review and meta-analysis.

BACKGROUND: The acute and long-term benefits of exercise training on cardiovascular health have been well established. The systematic review and meta-analysis aimed to systematically assess the effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women with elevated blood pressure. METHODS: A comprehensive search was conducted on PubMed, Embase, Web of Science, ProQuest, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov website from inception to September 30, 2023, to identify the randomized controlled trials (RCTs), which evaluated the effectiveness of exercise training on arterial stiffness and blood pressure in postmenopausal women. Standardized mean differences (SMD), weighted mean differences (WMD), and 95% confidence intervals (95% CIs) were calculated using random/fixed effects models. Quality assessment was performed using the modified Jadad scale and the Cochrane Risk of Bias Tool. Sensitivity analysis and subgroup analysis were conducted based on drug dosage, treatment duration, and age of administration to further explore potential heterogeneity. Funnel plots were performed to assess publication bias and Begg's regression test was carried out for funnel plot asymmetry. RESULTS: Twenty-two RCTs involving 1978 participants were included in the quantitative analysis. The mean quality of eligible studies was 4.2 out of 7 based on the modified Jadad scale. The results indicated that exercise training had a significant effect on reducing brachial-ankle pulse wave velocity [MD = - 0.69, 95%CI (- 1.11, - 0.27), P = 0.001], decreasing augmentation index (AIx) [MD = - 6.00, 95%CI (- 6.39, - 5.61), P < 0.00001] and AIx normalized to a heart rate of 75 beats per minute (AIx@75%) [MD = - 7.01, 95%CI - 7.91 to - 6.12, P < 0.00001], lowering systolic blood pressure [MD = - 6.19, 95%CI - 9.24 to - 3.15, P < 0.0001], diastolic blood pressure [MD = - 3.57, 95%CI (- 6.10, - 1.03), P = 0.006) and pulse pressure [MD = - 8.52, 95%CI (- 16.27, - 0.76), P = 0.03]. Subgroup analysis revealed that baseline blood pressure levels had a large impact on the effect of exercise training. CONCLUSIONS: The systematic review and meta-analysis suggested that exercise training may ameliorate arterial stiffness and reduce blood pressure in postmenopausal women with elevated blood pressure. However, the optimal mode of exercise training that improves arterial stiffness and blood pressure in this population requires further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021211268.

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 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.

Systemic hemodynamics and pediatric lung disease: Mechanistic links and therapeutic relevance.

Chronic lung disease, also known as bronchopulmonary dysplasia affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focussed on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation.

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.

The predictive value of estimated pulse wave velocity (ePWV) combined with BMI for newly diagnosed diabetes.

PURPOSE: Estimated pulse wave velocity (ePWV) and body mass index (BMI) are significant predictors of new-onset diabetes. This study aims to evaluate the impact and predictive value of combining ePWV and BMI on the incidence of new-onset diabetes. METHODS: A secondary analysis was conducted on a cohort study by Rich Healthcare (China), involving 211,833 eligible participants. Logistic regression analysis identified factors influencing diabetes occurrence, while ROC curve analysis assessed the predictive value of ePWV, BMI, and their combination for new-onset diabetes. RESULTS: Over a mean follow-up period of 3.12 years, 3,000 men (1.41%) and 1,174 women (0.55%) were diagnosed with diabetes. Logistic regression revealed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and family history of diabetes are high-risk factors for new-onset diabetes. The combination of ePWV and BMI provided a higher area under the ROC curve (0.822) compared to ePWV or BMI alone. CONCLUSION: Elevated levels of ePWV and BMI are independent risk factors for new-onset diabetes. Combining these measures enhances predictive accuracy compared to using either indicator alone.

Sex differences and Role of Lysyl Oxidase Like 2 (LOXL2) in Angiotensin II-Induced Hypertension in Mice.

INTRODUCTION: Hypertension, a disease with known sexual dimorphism, accelerates aging associated arterial stiffening. In this study, we tested the effect of biological sex and the role of the matrix remodeling enzyme lysyl oxidase like 2 (LOXL2) in hypertension induced arterial stiffening. METHODS: Hypertension was induced by Angiotensin II (AngII) infusion. Blood pressure and pulse wave velocity (PWV) were measured noninvasively. Wire myography and uniaxial tensile testing were used to test aortic vasoreactivity and mechanical properties. Aortic wall composition was examined by histology and Western blotting. Uniaxial stretch of cultured cells was used to evaluate the effect of biomechanical strain. LOXL2's catalytic function was examined using knockout and inhibition. RESULTS: Ang II infusion induced hypertension in both genotypes and sexes. Hypertensive WT males had higher PWV and passive stiffness. Aortic remodeling with increased wall thickness, intralamellar distance, higher LOXL2, collagen I, and collagen IV content was noted in WT males. Females did not exhibit increased PWV. LOXL2-depletion improved aortic mechanics in both sexes. LOXL2-depletion improved hyper-contractility in males but not females. Hypertensive cyclic strain contributed to LOXL2 upregulation in the cell-derived matrix in VSMCs. LOXL2's catalytic function facilitated VSMC alignment in response to biomechanical strain. CONCLUSION: In males, arterial stiffening in hypertension is driven by VSMC response and matrix remodeling; females are protected from stiffening independent of LOXL2. VSMCs are the primary source of LOXL2 in the aorta. Hypertension increases LOXL2 processing and collagen I accumulation in the aorta. Overall, LOXL2 depletion offers protection in young hypertensive males and females.

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 .

Effects of five types of exercise on vascular function in postmenopausal women: a network meta-analysis and systematic review of 32 randomized controlled trials.

Background: As women age, especially after menopause, cardiovascular disease (CVD) prevalence rises, posing a significant global health concern. Regular exercise can mitigate CVD risks by improving blood pressure and lipid levels in postmenopausal women. Yet, the optimal exercise modality for enhancing vascular structure and function in this demographic remains uncertain. This study aims to compare five exercise forms to discern the most effective interventions for reducing cardiovascular risk in postmenopausal women. Methods: The study searched PubMed, Web of Science, Cochrane, EBSCO, and Embase databases. It conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) on five exercise interventions: continuous endurance training (CET), interval training (INT), resistance training (RT), aerobic combined with resistance training (CT), and hybrid-type training (HYB). Outcome measures included carotid artery intima-media thickness (IMT), nitric oxide (NO), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) of the brachial artery. Eligible studies were assessed for bias using the Cochrane tool. A frequentist random-effects NMA was employed to rank exercise effects, calculating standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: The analysis of 32 studies (n = 1,427) indicates significant increases in FMD with CET, INT, RT, and HYB in postmenopausal women. Reductions in PWV were significant with CET, INT, RT, CT, and HYB. AIx decreased significantly with INT and HYB. CET, INT, and CT significantly increased NO levels. However, no significant reduction in IMT was observed. SUCRA probabilities show INT as most effective for increasing FMD, CT for reducing PWV, INT for decreasing AIx, CT for lowering IMT, and INT for increasing NO in postmenopausal women. Conclusion: The study demonstrates that CET, INT, RT, and HYB have a significant positive impact on FMD in postmenopausal women. Furthermore, all five forms of exercise significantly enhance PWV in this population. INT and HYB were found to have a significant positive effect on AIx in postmenopausal women, while CET, INT, and CT were found to significantly improve NO levels. For improving vascular function in postmenopausal women, it is recommended to prioritize INT and CT exercise modalities. On the other hand, as CET and RT were not ranked at the top of the Sucra value ranking in this study and were less effective than INT and CT as exercise interventions to improve vascular function in postmenopausal women, it is not recommended that CET and RT be considered the preferred exercise modality.

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.

Long term worsening of arterial stiffness from monitoring of QKD interval predicts the occurrence of cardiovascular events.

Arterial stiffness is an independent predictor of cardiovascular events in different populations. Destiffening appears to be possible through the control of the main cardiovascular risk factors, with however important individual variations. There are so far too few data available on the prognostic importance of changes in arterial stiffness. We tested the consequences of changes in arterial stiffness assessed with the QKD method on the incidence of cardiovascular events in a cohort of hypertensive patients. The change of QKD100-60 was calculated as the difference between baseline and last follow-up value. Patients were classified as group 0 with stable or increased QKD100-60 and group 1 with decreased QKD100-60 (increased arterial stiffness). The prognostic of these two groups was analysed with a Cox model including age, baseline QKD100-60, 24 h SBP (baseline and change), delay between first and last recording, sex, diabetes, smoking, and hypercholesterolemia. We included 555 essential hypertensive patients with 24 h ambulatory measurement of BP and QKD at baseline and follow-up. The follow-up period was 12.28 ± 7.38 years with an average time between baseline and last recording of 8.86 ± 6.48 years. 94 cardiovascular events occurred. The group with increased arterial stiffness shows the double risk of occurrence of cardiovascular event than the group with stable or reduced arterial stiffness independently of other factors including changes in 24 h SBP.

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.

Impact of Periodontitis on Endothelial Risk Dysfunction and Oxidative Stress Improvement in Patients with Cardiovascular Disease.

Periodontitis is a multifactorial chronic inflammatory disease that affects the periodontium and overall oral health and is primarily caused by a dysbiotic gingival biofilm, which includes, among others, Gram-negative bacteria such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Tannerella forsythensis that colonize gingival tissues and that can lead, if not properly treated, to periodontal tissue destruction and tooth loss. In the last few decades, several large-scale epidemiological studies have evidenced that mild and severe forms of periodontitis are strictly bilaterally associated with several cardiovascular diseases (CVDs), stroke, and endothelial dysfunction. Specifically, it is hypothesized that patients with severe periodontitis would have compromised endothelial function, a crucial step in the pathophysiology of atherosclerosis and several CVD forms. In this regard, it was postulated that periodontal treatment would ameliorate endothelial dysfunction, hence bolstering the notion that therapeutic approaches targeted at diminishing cardiovascular risk factors and different forms of periodontal treatment could improve several CVD biomarker outcomes in the short- and long-term in CVD patients. The aim of this review is to update and analyze the link between periodontitis and CVD, focusing on the inflammatory nature of periodontitis and its correlation with CVD, the effects of periodontal therapy on endothelial dysfunction and oxidative stress, and the impact of such therapy on CVD biomarkers and outcomes. The article also discusses future research directions in this field.

Prognostic value of brachial-ankle pulse wave velocity changes post-transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) offers a solution, especially for high-risk aortic stenosis (AS) patients. However, patient outcomes post-TAVR show variability, highlighting the need for reliable prognostic indicators. Brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, may predict outcomes post-TAVR. This study aims to explore baPWV's prognostic value in relation to all-cause mortality post-TAVR. This study prospectively enrolled 212 severe AS patients undergoing TAVR between September 2015 and December 2021, focusing on pre- and post-TAVR baPWV measurements to explore associations with all-cause mortality. Of the 212 patients (119 females, 93 males, mean age 85 years), post-TAVR baPWV increased significantly from 1589 ± 376 to 2010 ± 521 cm/s (p < 0.001). Aortic valve (AV) peak velocity and mean pressure gradient decreased, while AV area increased, indicating procedural success. Despite this, 88% of patients experienced an increase in baPWV, with higher pre-procedure AV peak velocity and mean pressure gradient identified as predictors of increased baPWV post-TAVR. Over 23 months, 29 patients (14%) reached the primary endpoint of all-cause mortality. Notably, changes in baPWV, rather than baseline values, were significantly associated with event-free survival (HR: 0.64 per 1SD increase, p = 0.009). The study highlights the prognostic value of baPWV changes post-TAVR in predicting patient outcomes. Elevated baPWV post-TAVR may reflect a beneficial adaptation to altered hemodynamics, suggesting the need for individualized patient evaluation and the integration of baPWV measurements into clinical practice for improved post-TAVR management.

Chronic pain in multiple sites is associated with cardiovascular dysfunction: an observational UK Biobank cohort study.

BACKGROUND: Chronic pain is associated with development of cardiovascular disease. We investigated the association between how widespread chronic pain is and the development of cardiovascular dysfunction. METHODS: We analysed data from participants enrolled in the UK Biobank study who underwent examinations at baseline, plus first follow-up and two imaging visits. Pain sites (including hip, knee, back, neck/shoulder, or 'all over the body') and pain duration were recorded at each visit. Chronic pain was defined as pain lasting for ≥3 months. Participants were categorised into six groups: no chronic pain, chronic pain in one, two, three, or four sites, or 'all over the body'. Arterial stiffness index was measured at each time point. Carotid intima-media thickness, cardiac index, and left ventricular ejection fraction (LVEF) were measured using ultrasound and heart MRI at two additional imaging visits in a subset of participants. Mixed-effect linear regression models were used for the analyses. RESULTS: The number of chronic pain sites was directly related to increased arterial stiffness index (n=159,360; ß=0.06 per one site increase, 95% confidence interval 0.04 to 0.08). In 23,899 participants, lower LVEF was associated with widespread chronic pain (ß=-0.17 per one site increase, 95% confidence interval -0.27 to -0.07). The number of chronic pain sites was not associated with carotid intima-media thickness (n=30,628) or cardiac index (n=23,899). CONCLUSION: A greater number of chronic pain sites is associated with increased arterial stiffness and poorer cardiac function, suggesting that widespread chronic pain is an important contributor to cardiovascular dysfunction.

Role of Physical Activity and Sedentary Behaviors on Vascular and Myocardial Structure and Function in Type 1 Diabetes.

OBJECTIVE: To estimate associations between physical activity and sedentary behaviors and early markers of cardiovascular diseases (CVD) in adolescents with and without type 1 diabetes. STUDY DESIGN: Cross-sectional data stem from CARDEA, a study investigating early CVD development in 100 adolescents with type 1 diabetes recruited at Sainte-Justine University Hospital Diabetes Clinic and 97 healthy adolescents without diabetes (14-18 years), in Montréal, Canada. Outcomes included arterial stiffness by pulse-wave velocity, endothelial function (VTI) by flow-mediated dilation test, and cardiac magnetic resonance imaging markers. Moderate-to-vigorous physical activity (MVPA) and sedentary time were estimated by accelerometry and leisure screen time by questionnaire. We estimated multivariable linear regression models stratified by group. RESULTS: In adolescents with type 1 diabetes, 10-minutes daily increase in MVPA was associated with 3.69 g/m (95% CI: -1.16; 8.54) higher left ventricular (LV) mass/height and 1-h increase in device-measured sedentary time with 0.68 mm (0.20; 1.16) higher wall thickness but only in those with glycated hemoglobin ≤7.5%. In healthy adolescents, a 10-minute increase in MVPA was associated with 1.32 g/m (-0.03; 2.66) higher LV mass/height. Every 1-hour increase in sedentary time was associated with -1.82 cm (-3.25; -0.39) lower VTI, -2.99 g/m (-5.03; -0.95) lower LV mass/height, and -0.47 mm (-0.82; -0.12) lower wall thickness. CONCLUSIONS: Being active and limiting sedentary time appears beneficial for cardiac structure and endothelial function in healthy adolescents; however adequate glycemic control combined with higher levels of MVPA may be required for adolescents with type 1 diabetes to overcome the impact of diabetes.

Acute Effects of Cadence-Controlled Walking on Cognition and Vascular Function in Physically Inactive Older Adults: A Randomized Crossover Study.

BACKGROUND: Cadence-controlled walking may be a desirable approach for older adults to self-monitor exercise intensity and achieve physical activity guidelines. We examined the acute effects of cadence-controlled walking on cognition and vascular function in physically inactive older adults. METHODS: In a randomized crossover design, 26 participants (65% females, 67.8 ± 11.3 years) underwent 30-min acute exercise (walking at 100 steps/min) and control (sitting) conditions. We measured cognition, central blood pressure (BP), and arterial stiffness before, and immediately, after each condition. RESULTS: We observed significant Time × Condition interactions in the Flanker Inhibitory Control and Attention (Flanker) test and Dimensional Change Card Sort (DCCS) test scores, and in central systolic BP, central pulse pressure, and carotid to femoral pulse wave velocity (p < .05). The Flanker and DCCS scores significantly increased after walking (d = 0.4 and 0.5, respectively), but not after sitting. Central systolic BP, central pulse pressure, and carotid to femoral pulse wave velocity significantly increased after sitting but remained unchanged after acute walking (d = 0.4-0.2), with p-values < .05. After walking, significant correlations were observed between DCCS and diastolic BP and central pulse pressure change scores and change scores in central pulse wave velocity, Flanker, and DCCS (rs = -0.45 to -0.52). CONCLUSION: These findings suggest that a single bout of cadence-controlled walking elicited an immediate improvement in cognition and might have mitigated increases in arterial stiffness and central BP observed in the seated control condition. Further research is needed to examine the association between cognition and vascular function following acute exercise compared to control conditions. SIGNIFICANCE: Our findings may have practical implications for developing daily physical activity recommendations for improving the cognitive health for successful aging.