This study aimed to develop a chronic proximal thoracic aortic aneurysm (PTAA) model by combining periaortic elastase application with oral administration of 3-aminopropionitrile fumarate salt (BAPN) after surgery. Sixty 8-week-old C57BL/6J male mice were divided into four groups: Sham, Sham + BAPN, Elastase, and Elastase + BAPN. High-resolution micro-ultrasound was performed on days 7, 14, 21, 28, 56, and 90 post-operation to measure aortic diameter. Histopathological, transcriptomic, and bioinformatics analyses were conducted to assess the model's relevance to human PTAA. The operative mortality rate was 10 % (6/60). During follow-up, 4 animals in the elastase + BAPN group and 1 in the elastase group died from aortic rupture. Significant continuous dilation of the proximal thoracic aorta was observed only in the elastase + BAPN group, with average dilation rates of 116.60 %, 178.99 %, and 231.90 % on days 28, 56, and 90, respectively, compared to 66.46 %, 61.13 %, and 68.73 % in the elastase group. Histopathology revealed greater aortic wall thickening, collagen deposition, MMP2 expression, elastin degradation, smooth muscle cell loss, calcification, and immune cell infiltration in the elastase + BAPN group. Transcriptomic analysis identified 3039 differentially expressed genes, enriched in immune and inflammation-related pathways. Weighted gene co-expression network analysis showed significant overlap in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment results between human and murine PTAA-related gene modules which were most positively correlated with PTAA diameters. This study establishes a chronic PTAA model that mimics key features of human disease, providing a valuable tool for investigating PTAA mechanisms and developing new therapies.

This study aimed to explore and compare the role of cumulative exposure to four blood pressure (BP) markers [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP)] in predicting cardiovascular disease (CVD) risk in the Uyghur population.

We recruited 3,553 Uyghurs from Tumxuk City, and conducted blood pressure measurements on them at least three times, with a minimum interval of two years between consecutive measurements. Cumulative BP was defined as the sum of the product of the average BP between consecutive examinations and the time interval between visits. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to estimate the association between cumBP and CVD risk. The incremental predictive value of cumBP was further assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).

Over a median follow-up of 6.29 years, 383 (10.78%) incidents of CVD occurred. All four cumBP markers were associated with CVD risk, with cumulative SBP (cumSBP) and cumulative PP (cumPP) showing the strongest associations. For each 1-SD increase in cumSBP and cumPP, the CVD risk increased by 31% [HR (95% CI): 1.310 (1.153, 1.489)] and 28% [HR (95% CI): 1.284 (1.132, 1.457)], respectively. Additionally, 1-SD values corresponded to 107.90 mmHg·years for cumSBP and 65.33 mmHg·years for cumPP. RCS analysis showed a linear relationship between cumBP and CVD risk. CumSBP provided the best incremental predictive value for CVD after adding cumSBP to the conventional model, improving the NRI by 0.126 (P = 0.019) and the IDI by 0.009 (P = 0.001). Although cumulative MAP and cumulative PP also improved the predictive capabilities to varying degrees, the effect sizes were smaller than those of cumSBP.

All four cumBP markers were significantly associated with CVD risk in this population. Compared with the other three cumBP measures, cumSBP had the strongest association with CVD events and provided a superior incremental predictive value for CVD events.

This study explores the feasibility of continuous pulse wave velocity (PWV) monitoring during general anaesthesia (GA), particularly in response to blood pressure fluctuations. Our aim is to evaluate whether dynamic PWV can provide new insight to detect cardiovascular risks. From December 2022 to February 2023, continuous carotid and femoral Doppler monitoring was performed on patients scheduled for surgery with GA, to collect PWV data at awakening (PWVAW) and during GA (PWVGA). The study investigated PWV's response to MAP fluctuations using the α-angle, a dynamic stiffness parameter. We evaluated PWV and α-angle efficacy in discriminating between low (CVR-) and high (CVR+) cardiovascular risk patients. Among 43 patients, 41 (95%) had successful PWV measurements. PWVAW was significantly higher than PWVGA (8.1 vs. 7.4 m.s-1, p < 0.0001). This difference vanished after matching MAP levels. A strong correlation was found between PWVAW and PWVGA (r = 0.88, and r = 0.97 at the same MAP levels). PWVGA, α-angle and their product (α x PWVGA) were significantly higher in CVR + patients (8.1 vs. 6.9 m.s-1, p < 0.01; 2.6 vs. 1.3 degrees, p < 0.001; 21.8 vs. 8.1 degrees.m.s-1, p < 0.001, respectively), with AUC values indicating good predictive capabilities for cardiovascular risk (PWVGA: AUC [95%CI] = 0.80 [0.65-0.95]; α-angle: 0.83 [0.69-0.96]; product: 0.86 [0.74-0.97]). Measurement of PWV under GA using carotid and femoral Doppler is a feasible method to continuously assess arterial stiffness under general anaesthesia. Further studies are required to validate the α-angle parameter in different physiological conditions.

The aim of this study was to determine whether pulse pressure (PP), an indicator of arterial stiffness, was independently associated with the risk of acute kidney injury (AKI) following intracerebral hemorrhage (ICH). We enrolled patients with acute ICH from a multicenter stroke registry in Fukuoka, Japan, from June 2007 to September 2019. The mean PP, measured three times on the third day after admission, was categorized into three groups based on tertiles: G1 < 54 mmHg, G2 54-64 mmHg, and G3 ≥ 65 mmHg. AKI was defined as an increase of ≥0.3 mg/dL or ≥150% in serum creatinine levels above baseline during hospitalization. The associations between PP and AKI were evaluated using logistic regression analyses. Overall, 1512 patients with acute ICH (mean age: 69.8 ± 13.5 years; 56.4% men) were included in the analysis. The incidence rates of AKI were 5.6%, 11.0%, and 13.2% in groups G1, G2, and G3, respectively. The odds ratio (95% confidence interval) of AKI was significantly elevated in G2 (1.77 [1.07-2.91]) and G3 (1.82 [1.10-3.03]) compared to G1, even after adjusting for initial systolic blood pressure (SBP) values on admission and subsequent SBP reductions. This significant association was observed in patients with an initial SBP < 200 mmHg (P for heterogeneity, 0.045) and those receiving intravenous antihypertensive therapy in the acute stage (P for heterogeneity, 0.03). High PP should be recognized as a novel potential risk factor for AKI following ICH. High pulse pressure was significantly associated with an increased risk of acute kidneyinjury following intracranial hemorrhage. Pulse pressure should be recognized as anovel potential risk factor and one of the predictors of acute kidney injury afterintracranial hemorrhage.

Genome-wide association studies (GWAS) have identified over 1,000 blood pressure (BP) loci and over 80 loci for Alzheimer's disease (AD). Considering BP is an AD risk factor, identifying pleiotropy in BP and cognitive performance measures may indicate mechanistic links between BP and AD.

Genome-wide scans for pleiotropy in BP variables-systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP)-and co-calibrated scores for cognitive domains (executive function, language, and memory) were performed using generalized linear mixed models and 116,075 longitudinal measures from 25,726 participants of clinic-based and prospective cohorts. GWAS was conducted using PLACO to estimate each SNP's main effect and interaction with age, and their joint effect on pleiotropy. Effects of genome-wide significant (GWS) pleiotropic SNPs on cognition as direct or mediated through BP were evaluated using Mendelian randomization. Potential contribution of genes in top-ranked pleiotropic loci to cognitive resilience was assessed by comparing their expression in brain tissue from pathologically confirmed AD cases with and without clinical symptoms.

Pleiotropy GWAS identified GWS associations with APOE and 11 novel loci. In the total sample, pleiotropy was identified for SBP and language with JPH2 ( P Joint =6.09×10 -9 ) and GATA3 ( P G×Age =1.42×10 -8 ), MAP and executive function with PAX2 ( P G×Age =4.22×10 -8 ), MAP and language with LOC105371656 ( P G×Age =1.75×10 -8 ), and DBP and language with SUFU ( P G =2.10×10 -8 ). In prospective cohorts, pleiotropy was found for SBP and language with RTN4 ( P G×Age =1.49×10 -8 ), DBP and executive function with ULK2 ( P Joint =2.85×10 -8 ), PP and memory with SORBS2 ( P G =2.33×10 -8 ), and DBP and memory with LOC100128993 ( P G×Age =2.81×10 -8 ). In clinic-based cohorts, pleiotropy was observed for PP and language with ADAMTS3 ( P G =2.37×10 -8 ) and SBP and memory with LINC02946 ( P G×Age =3.47×10 -8 ). Five GWS pleiotropic loci influence cognition directly, and genes at six pleiotropic loci were differentially expressed between pathologically confirmed AD cases with and without clinical symptoms.

Our results provide insight into the underlying mechanisms of high BP and AD. Ongoing efforts to harmonize BP and cognitive measures across several cohorts will improve the power of discovering, replicating, and generalizing novel associations with pleiotropic loci.

Tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) receptor signalling are used in cancer therapy to inhibit angiogenesis. Unfortunately, VEGF inhibitors are known to induce severe hypertension in patients. This study aimed to elucidate the impact of the TKI lenvatinib on blood pressure, arterial stiffness, vascular reactivity, as well as cardiac function in a short-term murine model to shed light on potential contributors to cardiovascular (CV) toxicities associated with VEGF inhibition.

Male C57BL/6J mice were randomly divided into 2 cohorts, either treated for 4 days with lenvatinib 4 mg/kg/day or 40% hydroxypropyl β-cyclodextrin as control. In an additional study, mice were subjected to a 4-day treatment followed by a 4-day wash-out, with echocardiography and blood pressure measurements performed on day 2 and 7. Subsequently, ex vivo vascular reactivity of thoracic aortic segments was determined.

Lenvatinib induced hypertension and arterial stiffness (i.e., increased pulse wave velocity), starting from day 2 of treatment. Further, left ventricular ejection fraction was reduced and the ventricle dilated upon treatment. Lenvatinib induced neither endothelial dysfunction nor impaired vascular smooth muscle cell reactivity to nitric oxide (NO). Interestingly, lenvatinib demonstrated a concentration-dependent increase in ATP-mediated relaxation. In addition, after the 4-day wash-out period, lenvatinib-treated mice did not show complete remission of hypertension. However, arterial stiffness, ATP-mediated relaxation and cardiac adaptation were recovered.

This comprehensive investigation provides valuable insights into the interplay between VEGF inhibition, vascular function and cardiac outcomes, emphasising the need for nuanced understanding and further exploration of the differential effects of lenvatinib on the CV system. Additionally, the study proposes a synergistic formation between VEGF and ATP, indicating an enhanced response via P2Yx receptor signalling.

Noise pollution is a known health risk factor and evidence for cardiovascular diseases associated with traffic noise is growing. At least 20% of the European Union's population lives in noise-polluted areas with exposure levels exceeding the recommended limits of the World Health Organization, which is considered unhealthy by the European Environment Agency. This results in the annual loss of 1.6 million healthy life years. Here, we investigated the protective effects of cardiovascular drug interventions against aircraft noise-mediated cardiovascular complications such as elevated oxidative stress or endothelial dysfunction. Using our established mouse exposure model, we applied mean sound pressure levels of 72 dB(A) for 4 d. C57BL/6 mice were treated with the beta-blocker propranolol (15 mg/kg/d s.c. for 5 d) or the alpha-blocker phenoxybenzamine (1.5 mg/kg/d s.c. for 5 d) and noise-exposed for the last 4 d of the drug administration. Short-term noise exposure caused hypertension (measured by tail-cuff blood pressure monitoring) and impaired endothelial function (measured by isometric tension recording in the aorta and video microscopy in cerebral arterioles in response to acetylcholine). Noise also increased markers of oxidative stress and inflammation. Treatment of mice with propranolol and phenoxybenzamine prevented endothelial and microvascular dysfunction, which was supported by a decrease in markers of inflammation and oxidative stress in heart tissue and the brain. Amelioration of noise-induced hypertension (systolic blood pressure) was not observed, whereas pulse pressure was lowered by trend. This study provides a novel perspective mitigating the adverse effects of noise pollution, especially in vulnerable groups with medication, a rationale for further pharmacological human studies.

Objective: The study aimed to assess the potential impacts of mean arterial pressure (MAP) and its determinants (cardiac output and systemic vascular resistance) on diabetic nephropathy (DNP)-associated impaired aortic function. Methods: This multi-ethnic study included 115 chronic kidney disease (CKD) patients (67 non-dialysis and 48 dialysis). Six aortic function measures were evaluated by SpygmoCor. The stroke volume was determined by echocardiography. Results: Hypertensive nephropathy (HNP) (53.9%), DNP (32.2%), glomerulonephritis (19.1%), and HIV-associated nephropathy (7.8%) composed the major CKD etiologies. Concurrent HNP and DNP were present in 31.1% of the patients. Participants with compared with those without concurrent HNP and DNP experienced more frequent established cardiovascular disease (43.2% versus 14.9%, p = 0.01), a faster pulse wave velocity (p = 0.001), and smaller total arterial compliance as an indicator of proximal aortic stiffness (p = 0.03). DNP was associated with each aortic function measure (p < 0.001-0.02) independent of potential confounders and MAP, as well as its determinants. HNP was not related to aortic function (p > 0.05 for all relationships). MAP and its determinants did not mediate the potential impact of DNP on aortic function (-4.1-6.4% contribution). Covariates that were associated with impaired aortic function measures included MAP and its determinants (p < 0.001-0.01). Conclusions: Mean or distending arterial pressure and its determinants were associated with impaired aortic function in the overall CKD population. However, these hemodynamic factors did not mediate DNP-associated impaired aortic function. Our results suggest that blood pressure lowering can be anticipated to improve impaired aortic function in the overall CKD population but not when it is solely induced by DNP.

Hypertension is a common, long-term condition that tends to be associated with age and can lead to significant cardiovascular complications. This study aimed to identify factors influencing the longitudinal Pulse Pressure of hypertensive patients treated at Assosa General Hospital (AGH), Western Ethiopia.

A retrospective study design was conducted from 325 randomly selected HTN patients in the outpatient department (OPD) clinic at AGH during the follow-up period from January 2022 to January 2024. The analysis included exploratory data analysis and the application of a linear mixed model. This model was used to analyze the longitudinally measured pulse pressure in patients with hypertension. The appropriate variance-covariance structure chosen for this analysis was the unstructured (UN) format.

Among the 325 patients included in the study, 51.5% were female, and 54.2% were from urban areas. The variables: Age (p-value < 0.0001), Urban (p-value = 0.012), FHHTN (p-value < 0.0238), Stage-I HTN (p-value = 0.0403), Stage-II HTN (p-value = 0.0022), DM (p-value < 0.0001), CKD (p-value < 0.0001), Smoking (p-value < 0.0001), Enalapril + Nifedipine (p-value = 0.0249), and follow-up time (p-value < 0.0001) were significant factors for the progression of pulse pressure.

The profile plot showed that the patient's pulse pressure decreases slowly as follow-up time increases. Age, Residence, FHHTN, DM, CKD, Smoking status, and Stages of HTN were positively associated with pulse pressure, whereas Treatment type and follow-up time were negatively associated with pulse pressure. So, Healthcare providers should prioritize addressing the modifiable risk factors mentioned above to help mitigate the progression of blood pressure specifically pulse pressure in hypertensive patients.

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.

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.

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).

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.

Recent studies indicate that intensive blood pressure (BP) targets can be reached with less than two medications. This cross-sectional study, involving 4991 individuals from the Majiapu community, assessed the correlation between BP control and the burden of antihypertensive drugs. Participants on medication were categorized into controlled (BP < 140/90 mm Hg) and uncontrolled (BP ≥ 140/90 mm Hg) groups, with the former further divided into optimal (BP < 130/80 mm Hg) and good control (BP < 140/90 but >130/80 mm Hg) subgroups. Multivariate logistic regression analyzed factors affecting hypertension control across these BP categories. The study found that, 54% of participants had hypertension. Of those treated (62.5%), 55.7% achieved BP control, including 23.15% maintaining BP below 130/80 mm Hg. The average number of antihypertensive medications was 1.61 for the controlled group (with an average BP of 126.6/76 mm Hg) and 1.75 for the uncontrolled group (with an average BP of 150.6/84.0 mm Hg). Additionally, the average number of antihypertensive medications was 1.66 in the good control group and 1.55 in the optimal control group. The uncontrolled group had a higher mean systematic coronary risk estimation (SCORE) of 5.59, against 3.97 and 2.5 in the good and optimal control groups, respectively. Key factors linked to poor BP control included age over 65, male sex, obesity, and former smoking, whereas lipid-lowering medication use was associated with better control. In conclusions, patients needing fewer antihypertensive drugs to achieve stricter targets may have a lower risk profile. Notably, only a small proportion of treated patients are low-risk individuals who can easily achieve BP levels below 130/80 mm Hg.

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality, and highly prevalent in older age, underscoring the importance of its appropriate management. The population is ageing at an increasing rate, with those aged 80+ years being the fastest growing population characterized by high heterogeneity in terms of functionality and autonomy. The prevalence of hypertension rises with increasing age, due to a significant increase in SBP largely as a result of age-related stiffening of the aorta and other large arteries, affecting almost 80% of those aged 80+ years. Appropriate management of blood pressure in this population is a priority for clinicians. Frailty is a condition characterized by marked vulnerability to adverse health outcomes and is common among older adults including those with hypertension. Hypertension increases frailty level and at the same time, individuals with increasing frailty present with more drug-related adverse effects meaning they are less tolerant to blood pressure lowering by medication. Thus, frailty is a factor that should be integrated when treating hypertension in this population. The European Society of Hypertension 2023 Guidelines on the management of Hypertension are the first international guidelines to integrate the concept of adapting blood pressure management in older adults according to their frailty/functionality level, and to propose practical tools for the application of this concept in the daily practice of physicians and other healthcare professionals. The present article prepared by the European Society of Hypertension Working Group on Hypertension in Older Adults aims to further address some important aspects mentioned concisely in the 2023 European Society of Hypertension guidelines, in order to help physicians and other healthcare professionals including those practicing in primary care. To this end, this study discusses 12 'hot questions' which are answered with the help of the 2023 European Society of Hypertension Guidelines. We hope the present article and Working Group's actions will contribute to understanding and applying the ideal management of hypertension in this most vulnerable population.

Arterial pulsation is crucial for promoting fluid circulation and for influencing neuronal activity. Previous studies assessed the pulsatility index based on blood flow velocity pulsatility in relatively large cerebral arteries of human. Here, we introduce a novel method to quantify the volumetric pulsatility of cerebral microvasculature across cortical layers and in white matter (WM), using high-resolution 4D vascular space occupancy (VASO) MRI with simultaneous recording of pulse signals at 7T. Microvascular volumetric pulsatility index (mvPI) and cerebral blood volume (CBV) changes across cardiac cycles are assessed through retrospective sorting of VASO signals into cardiac phases and estimating mean CBV in resting state (CBV0) by arterial spin labeling (ASL) MRI at 7T. Using data from 11 young (28.4±5.8 years) and 7 older (61.3±6.2 years) healthy participants, we investigated the aging effect on mvPI and compared microvascular pulsatility with large arterial pulsatility assessed by 4D-flow MRI. We observed the highest mvPI in the cerebrospinal fluid (CSF) on the cortical surface (0.19±0.06), which decreased towards the cortical layers as well as in larger arteries. In the deep WM, a significantly increased mvPI (p = 0.029) was observed in the older participants compared to younger ones. Additionally, mvPI in deep WM is significantly associated with the velocity pulsatility index (vePI) of large arteries (r = 0.5997, p = 0.0181). We further performed test-retest scans, non-parametric reliability test and simulations to demonstrate the reproducibility and accuracy of our method. To the best of our knowledge, our method offers the first in vivo measurement of microvascular volumetric pulsatility in human brain which has implications for cerebral microvascular health and its relationship research with glymphatic system, aging and neurodegenerative diseases.

As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic.

We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma.

This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients.

Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05).

The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.

Background/Objectives: Mortality due to various non-communicable diseases, including hypertension, is increasing globally. Studies have reported that periodontitis, a chronic inflammatory disorder caused by oral pathogens, is a potential risk factor for hypertension. These pathogens can invade arterial walls, leading to vascular inflammation and endothelial dysfunction, which then increases the likelihood of developing hypertension. However, evidence of the association between periodontitis and hypertension remains limited. Therefore, the aim of this study is to determine whether periodontitis is associated with hypertension among adults in Rwanda. Methods: A cross-sectional study was carried out among 420 participants (hypertensive and non-hypertensive) at the University Teaching Hospital of Kigali (CHUK) and Ruhengeri Hospital in Rwanda. Periodontitis was assessed using clinical parameters: clinical attachment loss (CAL), bleeding on probing (BoP), and periodontal pocket depth (PDD). Hypertension was defined as a patient with a systolic or diastolic blood pressure (SBP/DBP) of ≥140/90 mmHg. Descriptive statistics, the Chi-square test, and logistical regression were performed using SPSS version 29 for statistical data analysis. Results: The prevalence of periodontitis was found to be 69.5% among hypertensive patients and 52.4% among non-hypertensive patients. Clinical attachment loss was 6.24 times (AOR = 6.24, 95% CI: 1.99-19.56) higher among hypertensive patients and the difference was significant (p = 0.001). Other periodontal parameters such as periodontal pocket depth and bleeding on probing showed a more significant association among hypertensive than non-hypertensive patients. Conclusions: Our study found a significant association between periodontitis and hypertension in Rwandan adults. However, further intervention studies are needed to explore causality and potential interventions.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between a stiff AA and reduced longitudinal strain and the subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). The proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in silico utilizing the Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with (A) an elastic AA, (B) a stiff AA, and (C) a stiff AA with a free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that could abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of the LV longitudinal strain are common in patients with HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

In an era marked by a global demographic shift towards an aging society, there is a heightened prevalence of chronic kidney disease (CKD) among older adults. The burden of CKD spans from kidney-related complications to impacting psychological well-being, giving rise to depressive symptoms and caregiver burnout. This article delves into CKD prevention strategies within the context of aging, contributing to the discourse by exploring its multifaceted aspects. The prevention of CKD in the older adults necessitates a comprehensive approach. Primary prevention is centered on the modification of risk factors, acknowledging the intricate interplay of various comorbidities. Secondary prevention focuses on early CKD identification. Tertiary prevention aims to address factors contributing to CKD progression and complications, emphasizing the importance of timely interventions. This comprehensive strategy aims to enhance the quality of life for individuals affected by CKD, decelerating the deterioration of functional status. By addressing CKD at multiple levels, this approach seeks to effectively and compassionately care for the aging population.

The synergistic negative effects of type 2 diabetes (T2DM) and hypertension increases all-cause mortality and the medical complexity of management, which disproportionately impact Hispanics who face barriers to healthcare access. The Salud y Vida intervention was delivered to Hispanic adults living along the Texas-Mexico Border with comorbid poorly controlled T2DM and hypertension. The Salud y Vida multicomponent intervention incorporated community health workers (CHWs) into an expanded chronic care management model to deliver home-based follow-up visits and provided community-based diabetes self-management education.

We conducted multivariable longitudinal analysis to examine the longitudinal intervention effect on reducing systolic and diastolic blood pressure among 3806 participants enrolled between 2013 and 2019. Participants were compared according to their program participation as either higher (≥ 10 combined educational classes and CHW visits) or lower engagement (<10 encounters). Data was collected between 2013 and 2020.

Baseline mean systolic and diastolic blood pressure were 138 and 81 mmHg respectively. There were overall improvements in systolic (-6.49; 95% CI = [-7.13, -5.85]; p < 0.001) and diastolic blood pressure (-3.97; 95% CI = [-4.37, -3.56]; p < 0.001). The higher engagement group had greater systolic blood pressure reduction at 3 months (adjusted mean difference = -1.8 mmHg; 95% CI = [-3.2, -0.3]; p = 0.016) and at 15 month follow-up (adjusted mean difference = -2.3 mmHg; 95% CI = [-4.2, -0.39]; p = 0.0225) compared to the lower engagement group.

This intervention, tested and delivered in a real-world setting, provides an example of how CHW integration into an expanded chronic care model can improve blood pressure outcomes for individuals with co-morbidities.

Loneliness is recognised as a risk factor for cardiovascular disease development. However, it is unclear whether loneliness itself or other closely related mental health symptoms, such as depression and social anxiety, are associated with the development of cardiovascular disease. In the present study, we examined the relationship between loneliness and several early cardiovascular disease markers in young adults, after controlling for depression and social anxiety. Sixty-six young adults (18-35 years old, Mage = 22.70; 75.8% females) completed psychological questionnaires and took part in several physiological tests assessing cardiovascular health (e.g., vascular function). Results revealed higher loneliness was significantly associated with shorter pulse transit time (β = - 0.70, p = 0.002; shorter pulse transit time is a subclinical marker for arterial stiffness). Additionally, results show that while loneliness and depression were both related to vascular dysfunction in young adults, the underlining physiological mechanisms through which they affect vascular function may be different. Specifically, higher loneliness was associated with increased arterial stiffness, whereas depression was associated with increased endothelial dysfunction (β = - 0.43, p = 0.04). Our findings indicate that presence of loneliness and depression in young adults may be accompanied by early indicators of poor cardiovascular health, such as arterial stiffness and endothelial dysfunction. Results from the study further support the link between loneliness and cardiovascular disease development.

Aneurysm number (An) is a novel prediction tool utilizing parameters of pulsatility index (PI) and aneurysm geometry. An has been shown to have the potential to differentiate intracranial aneurysm (IA) rupture status. The objective of this study is to investigate the feasibility and accuracy of An for IA rupture status prediction using Australian based clinical data.

A retrospective study was conducted across three tertiary referral hospitals between November 2017 and November 2020 and all saccular IAs with known rupture status were included. Two sets of An values were calculated based on two sets of PI values previously reported in the literature.

Five hundred and four IA cases were included in this study. The results demonstrated no significant difference between ruptured and unruptured status when using An ≥1 as the discriminator. Further analysis showed no strong correlation between An and IA subtypes. The area under the curve (AUC) indicated poor performance in predicting rupture status (AUC1 = 0.55 and AUC2 = 0.56).

This study does not support An ≥1 as a reliable parameter to predict the rupture status of IAs based on a retrospective cohort. Although the concept of An is supported by hemodynamic aneurysm theory, further research is needed before it can be applied in the clinical setting.

This study demonstrates that the novel prediction tool, An, proposed in 2020 is not reliable and that further research of this hemodynamic model is needed before it can be incorporated into the prediction of IA rupture status.

During systole, longitudinal shortening of the left ventricle (LV) displaces the aortic root toward the apex of the heart and stretches the ascending aorta (AA). An in silico study (Living Left Heart Human Model, Dassault Systèmes Simulia Corporation) demonstrated that stiffening of the AA affects myocardial stress and LV strain patterns. With AA stiffening, myofiber stress increased overall in the LV, with particularly high-stress areas at the septum. The most pronounced reduction in strain was noted along the septal longitudinal region. The pressure-volume loops showed that AA stiffening caused a deterioration in LV function, with increased end-systolic volume, reduced systolic LV pressure, decreased stroke volume and effective stroke work, but elevated end-diastolic pressure. An increase in myofiber contractility indicated that stroke volume and effective stroke work could be recovered, with an increase in LV end-systolic pressure and a decrease in end-diastolic pressure. Longitudinal and radial strains remained reduced, but circumferential strains increased over baseline, compensating for lost longitudinal LV function. Myofiber stress increased overall, with the most dramatic increase in the septal region and the LV apex. We demonstrate a direct mechanical pathophysiologic link between stiff AA and reduced longitudinal left ventricular strain which are common in patients with HFpEF.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Overnight increases in arterial stiffness associated with sleep-disordered breathing may adversely affect patients with acute heart failure. Thus, we investigated overnight changes in arterial stiffness and their association with sleep-disordered breathing in patients hospitalized for acute heart failure. Consecutive patients with acute heart failure were enrolled. All participants underwent overnight full polysomnography following the initial improvement of acute signs and symptoms of acute heart failure. The arterial stiffness parameter, cardio-ankle vascular index (CAVI), was assessed before and after polysomnography. Overall, 60 patients (86.7% men) were analyzed. CAVI significantly increased overnight (from 8.4 ± 1.6 at night to 9.1 ± 1.7 in the morning, P < 0.001) in addition to systolic and diastolic blood pressure (from 114.1 mmHg to 121.6 mmHg, P < 0.001; and from 70.1 mmHg to 78.2 mmHg, P < 0.001, respectively). Overnight increase in CAVI (ΔCAVI ≥ 0) was observed in 42 patients (70%). The ΔCAVI ≥ 0 group was likely to have moderate-to-severe sleep-disordered breathing (i.e., apnea-hypopnea index ≥15, 55.6% vs 80.9%, P = 0.047) and greater obstructive respiratory events (29.4% vs 58.5%, P = 0.041). In multivariable analysis, moderate-to-severe sleep-disordered breathing and greater obstructive respiratory events were independently correlated with an overnight increase in CAVI (P = 0.033 and P = 0.042, respectively). In patients hospitalized for acute heart failure, arterial stiffness, as assessed by CAVI, significantly increased overnight. Moderate-to-severe sleep-disordered breathing and obstructive respiratory events may play an important role in the overnight increase in cardio-ankle vascular index.

Progressive cerebral infarction (PCI) is a common complication in patients with ischemic stroke that leads to poor prognosis. Blood pressure (BP) can indicate post-stroke hemodynamic changes which play a key role in the development of PCI. The authors aim to investigate the association between BP-derived hemodynamic parameters and PCI. Clinical data and BP recordings were collected from 80 patients with cerebral infarction, including 40 patients with PCI and 40 patients with non-progressive cerebral infarction (NPCI). Hemodynamic parameters were calculated from the BP recordings of the first 7 days after admission, including systolic and diastolic BP, mean arterial pressure, and pulse pressure (PP), with the mean values of each group calculated and compared between daytime and nighttime, and between different days. Hemodynamic parameters and circadian BP rhythm patterns  were compared between PCI and NPCI groups using t-test or non-parametric equivalent for continuous variables, Chi-squared test or Fisher's exact test for categorical variables, Cox proportional hazards regression analysis and binary logistic regression analysis for potential risk factors. In PCI and NPCI groups, significant decrease of daytime systolic BP appeared on the second and sixth days, respectively. Systolic BP and fibrinogen at admission, daytime systolic BP of the first day, nighttime systolic BP of the third day, PP, and the ratio of abnormal BP circadian rhythms were all higher in the PCI group. PCI and NPCI groups were significantly different in BP circadian rhythm pattern. PCI is associated with higher systolic BP, PP and more abnormal circadian rhythms of BP.

Over the last few decades, research efforts have resulted in major advances in our understanding of the pathophysiology of hypertensive heart disease (HHD). This is the third part of a three-part review series. Here, we focus on the influence of high blood pressure on the micro- and macroalterations that occur in the vasculature in HHD. We also provide an overview of circulating cardiac biomarkers that may prove useful for a better understanding of the pathophysiology, development and progression of HHD, and may play a unique role in the diagnostic and prognostic evaluation of patients with HHD, taking into account their properties showing as abnormal long before the onset of the disease. In the conclusion, we propose an updated definition of HHD and a matrix for clinical classification, which we suspect will be useful in practice, allowing an individual approach to HHD patients.

The aim of this study was to assess the prevalence of hypertension and to investigate risk factors linked to hypertension in older adults. An observational study was conducted in a group of adults between 60 and 85 years of age, living in south-eastern Poland. In line with the specific inclusion criteria, 80 women and 29 men were enrolled for the study (109 adults). Participants' body weight, height, and body fat percentage (BFP) were assessed using a bioelectrical impedance analysis, blood pressure was measured using automated oscillometric sphygmomanometer, moderate-to-vigorous physical activity (MVPA) and sedentary time were assessed using a tri-axial accelerometer, whereas data related to socio-economic and lifestyle factors were collected using a self-report technique. Arterial hypertension was found at a rate of 16% in participants with normal body weight, 22% in those with overweight and 85% in those with obesity. Body mass index (BMI) and BFP correlated significantly with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The highest median SBP and DBP values were found in the group of participants with obesity, and the lowest values were identified in those with normal body weight. Out of all the investigated socio-economic risk factors linked to hypertension, education level was the only one that showed significant associations. A logistic regression analysis was performed to check which factors were most strongly associated with hypertension in the study group. The stepwise method showed that hypertension was more common in participants with a higher BMI, and BFP and in those who did not meet MVPA recommendation.

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population.

Participants with stage 1 hypertension ( n = 69,509) or normal BP ( n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis.

During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13-1.25) for primary outcome, 1.24 (95% CI, 1.05-1.46) for MI, 1.45 (95% CI, 1.33-1.59) for stroke, and 1.11 (95% CI, 1.04-1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85-0.96).

Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.

In the growing population of older patients with hypertension, limited evidence supports an association between lowering systolic blood pressure (SBP) and decreased adverse events. We aimed to investigate cardiovascular outcomes according to on-treatment SBP in older hypertensive patients.

This multicenter, retrospective study used data from the Korea University Medical Center database built on electronic health records from 2017 to 2022. Patients initiated on at least two antihypertensive drugs in combination were followed for three years. The patients were grouped by average on-treatment SBP in 10-mmHg increments from <110 to 160 mmHg or more. The primary outcome was a composite of all-cause death, myocardial infarction, stroke, and hospitalization due to heart failure.

A total of 6427 patients aged ≥75 years (mean age, 80 years) were identified. The incidence of the primary outcome was lowest in individuals with an SBP of 120-129 mmHg (14.0%, P  < 0.001), and the adjusted hazard ratio for the primary outcome showed a J-shaped relationship with on-treatment SBP. Achieving an SBP of 120-129 mmHg showed acceptable safety profiles, including electrolyte imbalance, acute kidney injury, new-onset atrial fibrillation, and new-onset dementia or Alzheimer's disease when compared to the group with SBP of 130-139 mmHg.

An average on-treatment SBP of less than 130 mmHg was associated with improved outcomes in older hypertensive patients without raising safety concerns. These findings support the target SBP of 130 mmHg in older patients, if tolerated.

Hypovolemic shock (HS), a clinical condition of insufficient blood perfusion and oxygenation in body tissues, is associated with immense morbidity and mortality. Treatment approaches include fluid replacement and surgical repair of reversible causes of hemorrhage; however, they cause irreversible blood perfusion loss, systemic inflammation, multiple organ failure, and death. Centhaquin citrate (CC) is an innovative centrally acting cardiovascular active agent that is initially intended as an antihypertensive drug. However, due to its positive ionotropic effect, Centhaquin citrate is being tested clinically as a resuscitative agent for the management of hypovolemic shock It acts at the α2B-adrenergic receptor to produce venous constriction followed by an increase in venous return to the heart. These actions are assumed to be capable of resuscitative activity observed by centhaquin citrate, through an increase in cardiac output and tissue perfusion. Pharmacokinetics investigations in animals and humans have shown that centhaquin citrate is well tolerated and has insignificant side effects. Therefore, centhaquin citrate seems to be a promising entity and gaining the interest of researchers to develop it as a resuscitative agent in HS. The review gives insight into the development of centhaquin citrate as a resuscitative agent and provides insight into the associated mechanism of action and molecular signalling to foster future research on CC for its clinical use in HS.

This study aimed to investigate the relationship between hypertension and Alzheimer's disease (AD) and demonstrate the key role of stroke in this relationship using mediating Mendelian randomization. AD, a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral abnormalities, severely affects the quality of life of patients. Hypertension is an important risk factor for AD. However, the precise mechanism underlying this relationship is unclear. To investigate the relationship between hypertension and AD, we used a mediated Mendelian randomization method and screened for mediating variables between hypertension and AD by setting instrumental variables. The results of the mediated analysis showed that stroke, as a mediating variable, plays an important role in the causal relationship between hypertension and AD. Specifically, the mediated indirect effect value for stroke obtained using multivariate mediated MR analysis was 54.9%. This implies that approximately 55% of the risk of AD owing to hypertension can be attributed to stroke. The results suggest that the increased risk of AD owing to hypertension is mediated through stroke. The finding not only sheds light on the relationship between hypertension and AD but also indicates novel methods for the prevention and treatment of AD. By identifying the critical role of stroke in the link between hypertension and AD, this study provides insights into potential interventions that could mitigate the impact of hypertension on AD. This could help develop personalized treatments and help improve the quality of life of patients with AD who suffer from hypertension.

Peripheral arterial disease (PAD) is a global health problem and associated with poor outcomes. It causes increased arterial stiffness. The association of PAD with aortic arterial stiffness was investigated in previous studies. However, there is limited data regarding the effect of peripheral revascularization on arterial stiffness. The aim of our study is to investigate the effect of peripheral revascularization on aortic stiffness parameters in patients with symptomatic PAD.

A total of 48 patients with PAD who underwent peripheral revascularization were included in the study. Echocardiography was performed before and after the procedure, and aortic stiffness parameters were obtained by using aortic diameters and arterial blood pressure measurements.

Post-procedural aortic strain (5.1 [1.3-14] vs. 6.3 [2.8-6.3], p = 0.009) and aortic distensibility (0.2 [0.0-0.9] vs. 0.3 [0.1-1.1], p = 0.001) measurements were significantly increased compared to pre-procedural values. Patients were also compared according to the lesion laterality, site and treatment methods. It was found that the change in aortic strain (p = 0.031) and distensibility (p = 0.043) were significantly higher in unilateral lesion compared to bilateral lesion. Also, the change in aortic strain (p = 0.042) and distensibility (p = 0.033) were significantly higher in iliac site lesion compared to superficial femoral artery (SFA) site lesion. Moreover, the change in aortic strain was significantly higher (p = 0.013) in patients treated with stent compared to only balloon angioplasty.

Our study showed that successful percutaneous revascularization significantly reduced aortic stiffness in PAD. The change in aortic stiffness was significantly higher in unilateral lesions, iliac site lesions and stent-treated lesions.

Arterial stiffness and hypertension are closely related in pathophysiology. Chronic high blood pressure (BP) can lead to arterial wall damage by mechanical stress, endothelial dysfunction, increased inflammation, oxidative stress, and renin-angiotensin-aldosterone system (RAAS) activation. Hypertension also increases collagen fiber production and accelerates elastin fiber degradation. Stiffened arteries struggle with BP changes, raising systolic BP and pulse pressure. The resulting increased systolic pressure further hardens arteries, creating a harmful cycle of inflammation and calcification. Arterial stiffness data can predict target organ damage and future cardiovascular events in hypertensive patients. Thus, early detection of arterial stiffness aids in initiating preventive measures and treatment plans to protect against progression of vascular damage. While various methods exist for measuring arterial stiffness, pulse wave velocity is a non-invasive, simple measurement method that maximizes effectiveness. Healthy lifestyle changes, RAAS blockers, and statins are known to reduce arterial stiffness. Further research is needed to ascertain if improving arterial stiffness will enhance prognosis in hypertensive patients.

Prolonged P-wave duration (PWD), which indicates atrial conduction delay, is a potent precursor of atrial fibrillation (AF) that may be induced by obstructive sleep apnea (OSA). The cardio-ankle vascular index (CAVI), which is an arterial stiffness parameter, is elevated in patients with OSA; moreover, an increased CAVI is associated with atrial conduction delay through left atrium enlargement in association with left ventricular diastolic dysfunction. We aimed to examine the relationship between the CAVI and PWD in patients with OSA.

We included patients with a sinus rhythm who underwent overnight polysomnography. We measured the PWD and CAVI on standard 12-lead electrocardiograms; further, we analyzed the relationship between PWD and CAVI.

We analyzed data from 300 participants (men, 89.0%; mean age, 52.3 ± 13.1 years; and body mass index, 26.2 ± 3.9 kg/m2). The mean PWD was 104.4 ± 10.4 ms while the mean CAVI was 7.5 ± 1.5. PWD was significantly correlated with CAVI (r = 0.478, p < 0.001); additionally, PWD and CAVI were directly associated with OSA severity (p = 0.002 and p = 0.002, respectively). Multivariate regression analysis revealed an independent significant correlation of PWD and CAVI with OSA severity.

In patients with OSA, an increase in arterial stiffness is associated with atrial conduction delay.

Arterial stiffness and cerebrovascular pulsatility are non-traditional risk factors of Alzheimer's disease. However, there is a gap in understanding the earliest mechanisms that link these vascular determinants to brain aging. Changes to mechanical tissue properties of the hippocampus (HC), a brain structure essential for memory encoding, may reflect the impact of vascular dysfunction on brain aging. We tested the hypothesis that arterial stiffness and cerebrovascular pulsatility are related to HC tissue properties in healthy adults across the lifespan. Twenty-five adults underwent measurements of brachial blood pressure (BP), large elastic artery stiffness, middle cerebral artery pulsatility index (MCAv PI), and magnetic resonance elastography (MRE), a sensitive measure of HC viscoelasticity. Individuals with higher carotid pulse pressure (PP) exhibited lower HC stiffness (β = -0.39, r = -0.41, p = 0.05), independent of age and sex. Collectively, carotid PP and MCAv PI significantly explained a large portion of the total variance in HC stiffness (adjusted R2 = 0.41, p = 0.005) in the absence of associations with HC volumes. These cross-sectional findings suggest that the earliest reductions in HC tissue properties are associated with alterations in vascular function.

Atherosclerotic disease, including stroke and myocardial infarction, is the leading cause of morbidity and mortality worldwide. Atherosclerotic plaque formation occurs in the setting of excess oxidative and hemodynamic stress and is perpetuated by smoking, poor diet, dyslipidemia, hypertension, and diabetes. Plaque may rupture, resulting in acute thrombotic events. Smoking cessation, lifestyle modification, risk factor optimization, and antithrombotic therapies are the mainstays of atherosclerotic disease management and are the cornerstones to reduce morbidity and mortality in this high-risk patient population. Novel therapeutics are in development and will add to the growing armamentarium available to physicians who manage atherosclerotic disease.