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Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage. Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words 'hypertension' and 'proteomics', and focused specifically on the most recent literature on the utility of proteomics in hypertension research. Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers. [ABSTRACT FROM AUTHOR]

Spinosad and temephos are two of the most used pesticides in Mexico for the control of vector causing disease such as dengue, chikungunya and Zika. The aim of this study was to compare the neurotoxic effects of these two pesticides using guppy fish (Poecilia reticulata) as a model organism. Guppies were exposed for 7 and 21 days to technical grade temephos and spinosad at 1.0 and 0.07 g/L, respectively, (10 and 0.5 mg/L of active substance; concentrations recommended by the Ministery of Health of the State (Secretaría de Salud de Nayarit (SSN) Mexico)). Subsequently, acetylcholinesterase activity (AChE) and acetylcholine concentrations (ACh) in muscle tissue were determined. Temephos exposure decreased AChE activity and increased ACh concentration, whereas exposure to spinosad only increased ACh concentration. Though cholinergic alterations were more severe in fish exposed to temephos, both pesticides were equally lethal during the first seven days after exposure. Nonetheless, temephos was more lethal after 21 days. [ABSTRACT FROM PUBLISHER]

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The Mediterranean diet (MD) plays an important role in delaying vascular aging. The main objective of this study was to analyze the association between adherence to the MD and vascular aging estimated with brachial-ankle pulse wave velocity (ba-PWV) in a Spanish population sample and the differences by sex., Methods: Cross-sectional descriptive study. A total of 3437 subjects from the EVA, MARK and EVIDENT studies participated. The ba-PWV was assessed with the Vasera VS-1500 ® device. Vascular aging was classified as healthy vascular aging (HVA), normal vascular aging (NVA) and early vascular aging (EVA) and adherence to the MD was assessed with the Mediterranean Diet Adherence Screener questionnaire., Results: The mean age was 60.15 ± 9.55 (60.09 ± 9.71 in women; 60.20 ± 9.43 in men). Overall, MD adherence was observed in 48.0% of subjects (40% in women; 54% in men). The mean value of ba-PWV was 14.38 ± 2.71 (women 14.24 ± 2.89; men 14.49 ± 2.56). In multinomial logistic regression a positive association was found overall between HVA and NVA (OR = 1.751, 95% CI: 1.411-2.174, p < 0.001) and between HVA and EVA (OR = 1.501, 95% CI:1.295-1.740, p < 0.001); in women between HVA and NVA (OR = 2. 055, 95% CI:1.456-2.901, p < 0.001) and between HVA and EVA (OR = 1.413, 95% CI:1.124-1.776; p = 0.003); and in men between HVA and NVA (OR = 1.551, 95% CI: 1.175-2.047, p = 0.002) and between HVA and EVA (OR = 1.549, 95% CI: 1.275-1.882; p < 0.001)., Conclusions: The results of this work indicate that greater adherence to the MD is associated with healthier vascular aging.

Objectives: The aim of the study was to examine the relationship between the Mediterranean diet (MD) and vascular stiffness and metabolic syndrome (MetS), as well as its components in individuals over the age of 65, overall and by sex., Methods: The subjects of the study were people over 65 years of age, with a full record of all variables analyzed from the EVA, MARK, and EVIDENT studies. Data from 1280 subjects with a mean age of 69.52 ± 3.58 years (57.5% men) were analyzed. The MD was recorded with the validated 14 item MEDAS questionnaire. MetS was defined following the guidelines of the joint scientific statement from the Programa Nacional de Educación sobre el Colesterol III. Vascular stiffness was evaluated with the VaSera VS-1500 ® device by measuring the cardio-ankle vascular index (CAVI) and the brachial-ankle pulse wave velocity (baPWV)., Results: The mean MEDAS score was 6.00 ± 1.90, (5.92 ± 1.92 in males, 6.11 ± 1.88 in females; p = 0.036). CAVI: 9.30 ± 1.11 (9.49 ± 1.05 males, 9.03 ± 1.13 females; p = <0.001). baPWV: 15.82 ± 2.56 (15.75 ± 2.46 males, 15.92 ± 2.68 females; p = <0.001). MetS was found in 51% (49% males, 54% females; p = 0.036). Subjects with MetS had lower MD adherence and higher vascular stiffness values than subjects without MetS. Overall, we found a negative association with MD score and the number of MetS components (β = -0.168), with glycemia (β = -0.007), triglycerides (β = -0.003), waist circumference (β = -0.018), CAVI (β = -0.196) and baPWV (β = -0.065), and a positive association with HDL cholesterol (β = 0.013). Regarding sex, associations followed the same direction but without reaching statistical significance with blood glucose and triglycerides in females and with HDL cholesterol and waist circumference in males., Conclusions: The results indicate that greater adherence to the Mediterranean diet decreases vascular stiffness and the percentage of subjects with MetS, although results differed in the association with MetS components by sex.

Latent autoimmune diabetes in adults (LADA) is characterized by the presence of glutamate decarboxylase autoantibodies (GADA). LADA has intermediate features between type 1 diabetes and type 2 diabetes. In addition, genetic risk factors for both types of diabetes are present in LADA. Nonetheless, evidence about the genetics of LADA in non-European populations is scarce. This study aims to perform a genome-wide association study with a phenome-wide association study of LADA in a southeastern Mexican population. We included 59 patients diagnosed with LADA from a previous study and 3121 individuals without diabetes from the MxGDAR/ENCODAT database. We utilized the GENESIS package in R to perform the genome-wide association study (GWAS) of LADA and PLINK for the phenome-wide association study (PheWAS) of LADA features. Nine polymorphisms reach the nominal association level (1 × 10 -5 ) in the GWAS. The PheWAS showed that rs7305229 is genome-wide and associated with serum GADA levels in our sample ( p = 1.84 × 10 -8 ). rs7305229 is located downstream of the FAIM2 gene; previous reports associate FAIM2 variants with childhood obesity, body mass index, body adiposity measures, lymphocyte CD8+ activity, and anti-thyroid peroxidase antibodies. Our findings reveal that rs7305229 affects the GADA levels in patients with LADA from southeastern Mexico. More studies are needed to determine if this risk genotype exists in other populations with LADA.

(1) The main aim of this study was to analyze the relationship of the Mediterranean diet (MD) with vascular function in participants with and without increased insulin resistance (IR) in the Spanish population. A secondary aim was to study differences by gender. (2) Methods: Data were analyzed from 3401 subjects in the EVA, MARK, and EVIDENT studies (mean age = 60 years and 57% men). IR was evaluated with the triglyceride and glucose index (TyG index). TyG index = Ln [(fasting triglyceride mg/dL × fasting glucose mg/dL)/2]. The MD was measured against the MEDAS questionnaire, with the 14 items used in the PREDIMED study. Vascular stiffness was estimated with the brachial-ankle pulse wave velocity (baPWV) and the cardio ankle vascular index (CAVI) using the Vasera VS-1500 ® . (3) Results: The mean MEDAS value was 5.82 ± 2.03; (men: 5.66 ± 2.06; women: 6.04 ± 1.99; p < 0.001). MD adherence was 36.8% (men: 34.2%; women: 40.3%; p < 0.001). The mean baPWV value was 14.39 ± 2.78; (men: 14.50 ± 2.65; women: 14.25 ± 2.93; p = 0.005). A baPWV value ≥ 14.5 m/s was found in 43.4% (men: 43.6%; women: 40.0%; p = 0.727). The mean CAVI value was 8.59 ± 1.28; (men: 8.75 ± 1.28; women: 8.37 ± 1.26; p < 0.001). CAVI values ≥ 9 were present in 39.0% (men: 44.4%; women: 31.7%; p < 0.001). The mean value of the TGC/G index was 10.93 ± 1.39; (men: 11.08 ± 1.33; women: 10.73 ± 1.43; p < 0.001). IR was found in 49.9%. The average value of the MD score value was negatively associated with baPWV and CAVI in all groups analyzed (<0.05), except in the group of women with insulin resistance. (4) Conclusions: The results suggest that MD adherence is negatively associated with the vascular stiffness parameters analyzed in all the groups studied except the group of women with insulin resistance.

Background: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA)., Methods: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA)., Measurements: cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing., Results: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant., Conclusions: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

The aim of this study was to analyze the relationship between healthy vascular aging (HVA) and the Mediterranean diet alongside other lifestyles in a Spanish population aged 35 to 75 years without previous cardiovascular diseases., Methods: In this cross-sectional descriptive study, 501 individuals aged 35 to 75 years were recruited from five health centers by random sampling stratified by age and sex (55.90 ± 14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor ® device, and carotid intima-media thickness using Sonosite Micromax ® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X ® accelerometer., Results: The mean VAI value was 61.23 ± 12.86 (men-63.47 ± 13.75 and women-59.04 ± 11.54; p < 0.001). HVA was found in 18.9% (men-19.9% and women-17.8%). In the multiple regression analysis after adjusting for possible confounding factors, the mean VAI value showed a positive association with alcohol use (β = 0.020) and sedentary hours per week (β = 0.109) and a negative association with hours of activity per week (β = -0.102) and with the number of healthy lifestyles (β = -0.640). In the logistic regression analysis, after adjusting for possible confounding factors and compared to those classified as non-HVA, subjects classified as HVA were more likely to show MD adherence (OR = 0.571), do more than 26 h per week of physical activity (OR = 1.735), spend under 142 h per week being sedentary (OR = 1.696), and have more than two healthy lifestyles (OR = 1.877)., Conclusion: The results of this study suggest that the more time spent doing physical activity and the less time spent in a sedentary state, the lower the vascular aging index and the greater the likelihood of being classified in the group of subjects with HVA.

The main objective of this work is to investigate the relationship between the Mediterranean diet (MD) and metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary objective is to analyze sex differences., Methods: A cross-sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, and a total of 3417 subjects with a mean age ± SD of 60.14 ± 9.14 years (57% men) were included. We followed the five criteria established in the National Cholesterol Education Program III to define MetS. The MD was assessed with the 14-item Mediterranean diet adherence screener (MEDAS) used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value., Results: The mean ± SD value of the MEDAS questionnaire was 5.83 ± 2.04 (men 5.66 ± 2.06 and women 6.04 ± 1.99; p < 0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p < 0.001). MetS was observed in 41.6% (39.0% men and 45.2% women; p < 0.001). In the multiple regression analysis, after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β = -0.336), and with the different components of MetS: systolic blood pressure (β = -0.011), diastolic blood pressure (β = -0.029), glycemia (β = -0.009), triglycerides (β = -0.004), and waist circumference (β = -0.026), except with the HDL-cholesterol value which showed a positive association (β = 0.021); p < 0.001 in all cases. In the logistic regression analysis performed, we found that an increase in MD adherence was associated with a decrease in the probability of MetS (OR = 0.56) and its components: blood pressure levels ≥ 130/85 mmHg (OR = 0.63), fasting plasma glucose ≥ 100 mg/dL (OR = 0.62), triglyceride levels ≥ 150 mg/dL (OR = 0.65), waist circumference levels ≥ 88 cm in women and ≥102 cm in men (OR = 0.74), and increased high-density lipoprotein cholesterol < 40 mg/dL in men and <50 mg/dL in women (OR = 1.70); p < 0.001 in all cases. The results by sex were similar, both in multiple regression and logistic regression., Conclusions: The results found in our work indicate that the greater the adherence to the MD, the lower the probability of presenting MetS. This result is repeated in the study by sex. More studies are needed to clarify that these results can be extended to the rest of the Mediterranean countries, and to other countries outside the Mediterranean basin.

Background: Behavioral and substance addictions are prevalent health problems that, alongside obesity, are linked to reduced physical activity and increased sedentary time. Similarly, arterial stiffness and vascular aging are processes that begin gradually at an early age and are closely associated with morbidity and mortality from cardiovascular diseases. The main objective of this study is to analyze how addictions are related to obesity and body fat distribution, physical activity, sedentary time, arterial stiffness and vascular aging, as well as sleep quality, cognitive function and gender differences in young adults aged between 18 and 34 years., Methods: This cross-sectional descriptive observational study will analyze data from 500 subjects (250 men and 250 women) aged 18-34 without cardiovascular disease, selected by simple random sampling with replacement from the urban population of the city center of Salamanca (34,044 people aged 18-34, with 18,450 women and 15,594 men). Behavioral and substance addictions, as well as sleep quality and cognitive impairment will be assessed using questionnaires. The Pittisburg Sleep Quality Index (PSQI) will be used to measure sleep quality and the Ford questionnaire will be used to measure insomnia in response to stress. For obesity, weight, height, waist and hip circumference, body composition will be measured with the Inbody 230 ® impedance meter. For physical activity and sedentary time, we will use the Actigraph ® accelerometer alongside the international physical activity questionnaire (IPAQ) and the Marshall questionnaire. The Sphygmocor System ® will be used for pulse wave analysis and carotid-femoral pulse wave velocity (cfPWV), while the Vasera VS-2000 ® will measure cardio ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Vascular aging will be calculated with the 10th and 90th percentiles of cfPWV or baPWV. Demographic, analytical variables will be collected, as will data to assess vascular, cardiac, renal, and brain injury., Discussion: Addictions are on the rise in today's society, affecting the mental health and well-being of those who suffer from them, generating important social problems such as job loss, family dysfunction, debt and social isolation. Together with obesity, they are prevalent health problems in young adults and are associated with lower physical activity and higher sedentary time. Meanwhile, arterial stiffness and vascular aging are processes that begin gradually at an early age and determine morbidity and mortality caused by cardiovascular diseases. The results of this project will allow us to understand the situation regarding behavioral and substance addictions in young adults. Better understanding of these addictions will in turn facilitate the development of more effective prevention strategies and intervention programs, which can then reduce the negative impact at both the individual and societal levels., Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT05819840]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vicente-Gabriel, Lugones-Sánchez, Tamayo-Morales, Vicente Prieto, González-Sánchez, Conde Martín, Gómez-Sánchez, Rodríguez-Sánchez, García-Ortiz, Gómez-Sánchez, Gómez-Marcos and EVA-Adic Investigators Group.)

Introduction: Personalized programs of integrated strength and balance activities have been shown their effectiveness in falls reduction in the older adults., Objective: To measure whether a group intervention with the strength and balance principles of the sLiFE program is more effective than standard health advice in reducing the incidence of falls., Methods: The study will comprise 650 participants with more than 65 years who live at home, observing established inclusion and exclusion criteria. Participants will be randomly assigned in two groups: group intervention ( n  = 325) and standard health advice ( n  = 325). The intervention group will follow the balance and strength activities described in the LiFE program manual. The group intervention will be carried out in groups of 12-14 and will consist of seven one-hour sessions over 12 weeks in health centres. Incidence of falls and quality of life will be assessed as primary outcome variables. Fear of falling and exercise adherence will be analysed as secondary outcome variables., Discussion: Physical activity has been put forward as an effective treatment technique for these patients; however, long-term adherence to these programs remains a challenge. Group interventions could reduce dropout rates., Conclusion: Falls represent a major health problem globally due to the disability they cause in older people. Prevention would help reduce not only their incidence but also the health costs derived from their treatment. Group intervention helps clinicians to save resources and time, being able to attend more people with the same quality of care., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05912088?distance=50&term=NCT05912088&rank=1, identifier NCT05912088., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Llamas-Ramos, Llamas-Ramos, Lugones-Sánchez, González-García, Tamayo-Morales, Alvarado-Omenat, Pablos-Hernández, Gómez-Marcos, García-Ortiz and Rodríguez-Sánchez.)

Background: Currently, vaccination of livestock with attenuated strains of Brucella remains an essential measure for controlling brucellosis, although these vaccines may be dangerous to humans. The aim of this study was to review the risk posed to humans by occupational exposure to vaccine strains and the measures that should be implemented to minimize this risk., Methods: This article reviewed the scientific literature indexed in PubMed up to September 30, 2023, following "the PRISMA guidelines". Special emphasis was placed on the vaccine strain used and the route of exposure. Non-occupational exposure to vaccine strains, intentional human inoculation, publications on exposure to wild strains, and secondary scientific sources were excluded from the study., Results: Nineteen primary reports were found and classified in three subgroups: safety accidents in vaccine factories that led to an outbreak (n = 2), survellaince studies on vaccine manufacturing workers with a serologic diagnosis of Brucella infection (n = 3), and publications of infection by vaccine strains during their administration, including case reports, records of occupational accidents and investigations of outbreaks in vaccination campaigns (n = 14). Although accidental exposure during vaccine manufacturing were uncommon, they could provoke large outbreaks through airborne spread with risk of spread to the neighboring population. Besides, despite strict protection measures, a percentage of vaccine manufacturing workers developed positive Brucella serology without clinical infection. The most frequent type of exposure with symptomatic infection was needle injury during vaccine administration. Prolonged contact with the pathogen, lack of information and a low adherence to personal protective equipment (PPE) use in the work environment were commonly associated with infection., Conclusions: Brucella vaccines pose occupational risk of contagion to humans from their production to their administration to livestock, although morbidity is low and deaths were not reported. Recommended protective measures and active surveillance of exposed workers appeared to reduce this risk. It would be advisable to carry out observational studies and/or systematic registries using solid diagnostic criteria., Competing Interests: All authors declare that not competing interests exists., (Copyright: © 2024 Vives-Soto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca 2+ ) handling alterations. Next, we investigated the role of the TWEAK-Fn14 axis in cardiomyocyte function following renal ischaemia-reperfusion (I/R) injury in mice. We observed that TWEAK-Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca 2+ handling and arrhythmogenic Ca 2+ events through an impairment in sarcoplasmic reticulum Ca 2+ -adenosine triphosphatase 2a pump (SERCA 2a ) and ryanodine receptor (RyR 2 ) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca 2+ cycling and arrhythmogenic events and prevented SERCA 2a and RyR 2 modifications. In conclusion, this study establishes the relevance of the TWEAK-Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca 2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: In this study we analyzed the association between physical activity and sedentary lifestyle with vascular aging in Spanish populations aged 35-75 years., Methods: A cross-sectional study was developed, in which 501 subjects aged 35-75 years were recruited. Physical activity and sedentary time were measured with an accelerometer (Actigraph GTX3) for a week. We measured carotid-femoral pulse wave velocity (cfPWV) by a Sphygmo Cor® device and carotid intima-media thickness (cIMT) by ultrasound (Sonosite Micromax®). The vascular aging index (VAI) was calculated as described in the literature. Vascular aging was defined considering the 25th and 75th percentiles by age and sex of cfPWV and VAI, presence of vascular injury, type-2 diabetes mellitus or arterial hypertension. Individuals were classified into three groups: healthy, normal, and early vascular aging., Results: The mean age of the sample was 55.90 ± 14.24 years, 50% being women. Total physical activity was negatively associated with cfPWV ( β = -0.454) and VAI ( β = -1.845). Similarly, the number of steps per day obtained a negative association with cfPWV ( β = -0.052) and VAI ( β = -0.216), while sedentary time showed a positive association with cfPWV ( β = 0.028) and VAI ( β = 0.117). In the analysis by sex, the results showed similar values. The odds ratio (OR) of total physical activity of subjects classified as early vascular aging (EVA) with regarding those classified as healthy vascular aging (HVA) was 0.521 (95% confidence interval [CI] 0.317 to 0.856) for cfPWV, and 0.565 (95% CI 0.324 to 0.986) for VAI. In terms of the number of steps per day, the OR was 0.931 (95% CI 0.875 to 0.992) for cfPWV and 0.916 (95% CI 0.847 to 0.990) for VAI and for sedentary time the OR was 1.042 (95% CI 1.011 to 1.073) for cfPWV and 1.037 (95% CI 1.003 to 1.072) for VAI. The OR of subjects classified as vigorous physical activity was 0.196 (95% CI 0.041 to 0.941) using cfPWV and 0.161 (95% CI 0.032 to 0.820) using VAI. In the analysis by sex, the results showed an association in men when cfPWV was used and an association in women when VAI was used to define vascular aging., Conclusions: The results of this study indicate that the more time spent performing physical activity and the less sedentary time, the lower the arterial stiffness and the probability of developing early vascular aging., Clinical Trial Registration: The study was registered in ClinicalTrials.gov (number: NCT02623894)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

The aim of this longitudinal descriptive observational study was to analyze the influence of different lifestyles on arterial stiffness (AS) throughout five years of follow-up and to describe the differences by sex in a Spanish adult population without cardiovascular disease at the start of the study. A random stratified sampling by age and sex was used to obtain 501 subjects included in the initial assessment. No cardiovascular disease was allowed in the subjects. The average age was 55.9 years, and 50.3% were women. A total of 480 subjects were analyzed again five years later. Alcohol and tobacco consumption were collected with standardized questionnaires. Adherence to the Mediterranean diet was assessed with the Mediterranean diet adherence screener (MEDAS) questionnaire. Physical activity was assessed with the short version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and sedentary time was assessed with the Marshall Sitting Questionnaire (MSQ). AS was assessed by measuring carotid-femoral pulse wave velocity (cfPWV) and central augmentation index (CAIx) with SphygmoCor System ® , and ankle pulse wave velocity (baPWV) and cardio ankle vascular index (CAVI) with Vasera VS-1500 ® . Increases in vascular function measures per year of follow-up were: cfPWV = 0.228 ± 0.360 m/s, baPWV = 0.186 ± 0.308 m/s, CAVI = 0.041 ± 0.181 m/s, and CAIx = 0.387 ± 2.664 m/s. In multiple regression analysis, positive association was shown between an increase in baPWV and tobacco index (β = 0.007) and alcohol consumption (β = 0.005). Negative association was shown between CAVI and Mediterranean diet score (β = -0.051). In multinomial logistic regression analysis, the OR of tobacco index of subjects with a cfPWV increase >P75 was OR = 1.025 and of subjects classified between P25 and P75 was OR = 1.026 regarding subjects classified with an increase P75 was OR = 1.006 regarding subjects classified with an increase P75, and an OR = 0.841 was found of subjects classified between P25-75 regarding subjects classified with an increase

Background: The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function., Methods and Analysis: MIVAS III is a multicenter cross-sectional study that will take place in the Iberian Peninsula. One thousand subjects aged between 45 and 74 years without cardiovascular disease will be selected. The main variables are demographic information, anthropometric measurements, and habits (tobacco and alcohol). Dietary patterns will be assessed using a frequency consumption questionnaire (FFQ) and the Mediterranean diet adherence questionnaire. Physical activity levels will be evaluated using the International Physical Activity Questionnaire (IPAQ), Marshall Questionnaire, and an Accelerometer (Actigraph). Body composition will be measured using the Inbody 230 impedance meter. Arterial aging will be assessed through various means, including measuring medium intimate carotid thickness using the Sonosite Micromax, conducting analysis with pulse wave velocity (PWA), and measuring pulse wave velocity (cf-PWV) using the Sphygmocor System. Additional cardiovascular indicators such as Cardio Ankle Vascular Index (CAVI), ba-PWV, and ankle-brachial index (Vasera VS-2000 ® ) will also be examined. The study will analyze the intestinal microbiota using the OMNIgene GUT kit (OMR-200) and profile the microbiome through massive sequencing of the 16S rRNA gene. Linear discriminant analysis (LDA), effect size (LEfSe), and compositional analysis, such as ANCOM-BC, will be used to identify differentially abundant taxa between groups. After rarefying the samples, further analyses will be conducted using MicrobiomeAnalyst and R v.4.2.1 software. These analyses will include various aspects, such as assessing α and β diversity, conducting abundance profiling, and performing clustering analysis., Discussion: Lifestyle acts as a modifier of microbiota composition. However, there are no conclusive results demonstrating the mediating effect of the microbiota in the relationship between lifestyles and cardiovascular diseases. Understanding this relationship may facilitate the implementation of strategies for improving population health by modifying the gut and oral microbiota., Trial Registration: clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lugones-Sánchez, Santos-Mínguez, Salvado, González-Sánchez, Tamayo-Morales, Hoya-González, Ramírez-Manent, Magallón-Botaya, Quesada-Rico, Garcia-Cubillas, Rodríguez-Sánchez, Gómez-Marcos, Benito-Sanchez, Mira, Hernandez-Rivas, Garcia-Ortiz and MIVAS III Researchers Group.)

The predictD is an intervention implemented by general practitioners (GPs) to prevent depression, which reduced the incidence of depression-anxiety and was cost-effective. The e-predictD study aims to design, develop, and evaluate an evolved predictD intervention to prevent the onset of major depression in primary care based on Information and Communication Technologies, predictive risk algorithms, decision support systems (DSSs), and personalized prevention plans (PPPs). A multicenter cluster randomized trial with GPs randomly assigned to the e-predictD intervention + care-as-usual (CAU) group or the active-control + CAU group and 1-year follow-up is being conducted. The required sample size is 720 non-depressed patients (aged 18-55 years), with moderate-to-high depression risk, under the care of 72 GPs in six Spanish cities. The GPs assigned to the e-predictD-intervention group receive brief training, and those assigned to the control group do not. Recruited patients of the GPs allocated to the e-predictD group download the e-predictD app, which incorporates validated risk algorithms to predict depression, monitoring systems, and DSSs. Integrating all inputs, the DSS automatically proposes to the patients a PPP for depression based on eight intervention modules: physical exercise, social relationships, improving sleep, problem-solving, communication skills, decision-making, assertiveness, and working with thoughts. This PPP is discussed in a 15-min semi-structured GP-patient interview. Patients then choose one or more of the intervention modules proposed by the DSS to be self-implemented over the next 3 months. This process will be reformulated at 3, 6, and 9 months but without the GP-patient interview. Recruited patients of the GPs allocated to the control-group+CAU download another version of the e-predictD app, but the only intervention that they receive via the app is weekly brief psychoeducational messages (active-control group). The primary outcome is the cumulative incidence of major depression measured by the Composite International Diagnostic Interview at 6 and 12 months. Other outcomes include depressive symptoms (PHQ-9) and anxiety symptoms (GAD-7), depression risk (predictD risk algorithm), mental and physical quality of life (SF-12), and acceptability and satisfaction ('e-Health Impact' questionnaire) with the intervention. Patients are evaluated at baseline and 3, 6, 9, and 12 months. An economic evaluation will also be performed (cost-effectiveness and cost-utility analysis) from two perspectives, societal and health systems., Trial Registration: ClinicalTrials.gov, identifier: NCT03990792., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bellón, Rodríguez-Morejón, Conejo-Cerón, Campos-Paíno, Rodríguez-Bayón, Ballesta-Rodríguez, Rodríguez-Sánchez, Mendive, López del Hoyo, Luna, Tamayo-Morales and Moreno-Peral.)

Multiple factors associate diabetes with cognitive impairment and depression. Antidiabetic drugs have reported antidepressant and pro-cognitive effects in diabetic and non-diabetic subjects. Antidepressant and pro-cognitive effects of metformin are reported in various studies; however, these effects are not consistent among researches. We designed a cross-sectional study. We recruited patients with T2D diagnosis from the Diabetes Clinic of the Regional Hospital of High Specialty "Dr. Gustavo A. Rovirosa Pérez" from January 2019 to May 2022. We included 431 subjects with T2D, 374 patients with metformin treatment and 57 subjects without metformin. These patients were on intensive therapies and had not a previous diagnosis of cognitive impairment or depression. We applied Mini-Mental State Examination (MMSE) to evaluate cognitive impairment, and Hamilton Depression Rating Scale (HAM-D) to assess depressive signs. Our sample had a mean age of 53.77 ± 13.43 years. Metformin users were 374 individuals, and 57 subjects didn't use metformin. MMSE found cognitive impairment in 8.3% (n = 31) of metformin users, and 14.8% (n = 8) of patients without metformin. HAM-D scale showed that 39.5% (n = 147) of patients with metformin had depression signs, subjects without metformin and depressive signs were 44.6% (n = 25). We found no differences between groups for cognitive impairment and depression grades. We did not find associations between metformin treatment, cognitive impairment measures and depression sign measures. However, chronic metformin treatment, insulin use, glycemic control and age could influence our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Latent autoimmune diabetes in adults (LADA) has clinical and metabolic features of type 1 and type 2 diabetes. LADA does not have specific features for its diagnosis apart from autoantibody detection; however, these tests are not affordable in clinical settings. In this cross-sectional study, we analyzed clinical criteria, metabolic control, pharmacological treatment, and diabetic complications in two groups of patients with diabetes -LADA and T2D- in order to identify specific characteristic of these clinical entities. Finally, we evaluated if the estimated glucose disposal rate (eGDR) and age at diagnosis of diabetes could be used as a diagnostic criterion for LADA. Demographic, biochemical, clinical and treatment were measured in 377 individuals with diabetes. The diagnostics of LADA were determined using Glutamic acid decarboxylase autoantibodies levels. Chi-square test or t-Student test were used to establish differences between groups. To identify factors associated with LADA, a logistic regression analysis was used. Finally, a ROC curve was plotted to assess the possible variables as diagnostic criteria for LADA. The 377 patients with diabetes were separated into 59 patients with LADA and 318 patients with T2D. Patients with LADA showed lower fasting glucose values, fewer diabetic complications, younger age at diagnosis of diabetes, higher insulin use, and higher eGDR in comparison to patients with T2D. Both groups had a mean BMI classified as overweight. The ROC evaluated the sensitivity and specificity, this analysis indicated that an age younger than 40.5 years and an eGDR value higher than 9.75 mg/kg/min correlated better with LADA. These parameters could be useful to identify patients suspected to have LADA at the first level of medical care in the population of southeastern Mexico and refer them to a second level of care., (© 2023. The Author(s).)

Calcific aortic stenosis (CAS) and type 2 diabetes mellitus (T2DM) are related and often concomitant pathologies, accompanied by common comorbidities such as hypertension or dyslipidemia. Oxidative stress is one of the mechanisms that trigger CAS, and it can drive the vascular complications in T2DM. Metformin can inhibit oxidative stress, yet its effects have not been studied in the context of CAS. Here, we assessed the global oxidative status in plasma from patients with CAS, both alone and with T2DM (and under treatment with metformin), using multimarker scores of systemic oxidative damage (OxyScore) and antioxidant defense (AntioxyScore). The OxyScore was determined by measuring carbonyls, oxidized LDL (oxLDL), 8-hydroxy-20-deoxyguanosine (8-OHdG), and xanthine oxidase (XOD) activity. In contrast, the AntioxyScore was determined through the catalase (CAT) and superoxide dismutase (SOD) activity, as well as the total antioxidant capacity (TAC). Patients with CAS displayed enhanced oxidative stress compared to control subjects, probably exceeding their antioxidant capacity. Interestingly, patients with CAS and T2DM displayed less oxidative stress, possibly due to the benefits of their pharmacological therapy (metformin). Thus, reducing oxidative stress or enhancing antioxidant capacity through specific therapies could be a good strategy to manage CAS, focusing on personalized medicine.

People living with dementia (PLWD) and their family caregivers report higher rates of having a sedentary lifestyle than their non-disabled peers do. This study analyzed the effectiveness of an intervention designed to increase physical activity among PLWD and their family caregivers in primary health care settings. A cluster-randomized multicenter clinical trial was conducted. Participants from four health centers were randomly assigned to the intervention group (IG) or the control group (CG) in a 1:1 ratio using Epidat software. After a seven-day period with a digital pedometer (Omron Hj-321 lay-UPS), participants were asked to complete the International Physical Activity Questionnaire Short Form (IPAQ-SF). PLWD and caregivers allocated to the IG were given brief advice, educational materials and an additional 15 min appointment to prescribe an individualized physical activity plan. Seventy PLWD and 80 caregivers were assigned to the CG and 70 PLWD and 96 caregivers were assigned to the IG. Results of the pedometer assessment show that in PLWD, the IG's activity increased by 52.89 aerobic steps at 6 months and the CG's activity decreased by 615.93 aerobic steps, showing a net increase in the IG of 668.82 (95% CI: -444.27 to 1781.91; p = 0.227). For caregivers in the IG, activity increased by 356.91 aerobic steps and in the CG it decreased by 12.95 aerobic steps, showing a net increase in favor of the IG of 369.86 (95%CI: -659.33 to 1399.05; p = 0.476). The effectiveness of interventions to increase physical activity in this group of people with dementia and their caregivers did not achieved positive results overall but may have provided suggestions for family physicians and physical therapists to improve physical activity among people with dementia and their families.

Acute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated with an alteration in the anti-aging factor klotho expression. However, it is unknown whether a klotho deficiency might aggravate cardiac damage after AKI. We examined intracellular calcium (Ca 2+ ) handling in native ventricular isolated cardiomyocytes from wild-type (+/+) and heterozygous hypomorphic mice for the klotho gene (+/ kl ) in which an overdose of folic acid was administered to induce AKI. Twenty-four hours after AKI induction, cardiomyocyte contraction was decreased in mice with the partial deletion of klotho expression (heterozygous hypomorphic klotho named +/kl ). This was accompanied by alterations in Ca 2+ transients during systole and an impairment of sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2a) function in +/kl mice after AKI induction. Moreover, Ca 2+ spark frequency and the incidence of Ca 2+ pro-arrhythmic events were greater in cardiomyocytes from heterozygous hypomorphic klotho compared to wild-type mice after AKI. A decrease in klotho expression plays a role in cardiorenal damage aggravating cardiac Ca 2+ mishandling after an AKI, providing the basis for future targeted approaches directed to control klotho expression as novel therapeutic strategies to reduce the cardiac burden that affects AKI patients.

Background: Cognitive impairment and dementia have a high prevalence among the elderly and cause significant socio-economic impact. Any progress in their prevention can benefit millions of people. Current data indicate that cardiovascular risk (CVR) factors increase the risk of developing cognitive impairment and dementia. Using models to calculate CVR specific for the Spanish population can be useful for estimating the risk of cognitive deterioration since research on this topic is limited and predicting this risk is mainly based on outcomes in the Anglo-Saxon population. The aim of this study is to assess the relationship between CVR in the Spanish population, as calculated using the FRESCO (Función de Riesgo Española de acontecimientos Coronarios y Otros) and REGICOR (Registre Gironí del Cor) CVR tables, and the change in cognitive performance at a 5-year follow-up., Methods: Design: Observational, analytic, prospective cohort study, with a 5-year follow-up. Ambit: Population. Population: Subjects 55 to 74 years of age, included in the NEDICES2 (2014-2017) cohort, who did not present dementia and had undergone the neuropsychological evaluation (N = 962). Variables: Exposure factors (CVR factors and estimated risk according to the CVR predictors by REGICOR and FRESCO), dependent variables (change in the score of the brief neuropsychological test in the study NEDICES2 five years after the first evaluation), and clinical and socio-demographic variables. Statistical analysis: Analysis of data quality. Descriptive analysis: socio-demographic and clinical variables of subjects. Bivariate analysis: relationship between basal CVR and change in neuropsychological tests. Multivariate analysis: relationship between basal CVR and change in neuropsychological tests adjusted by co-variables. Analysis and comparison of the reliable change in independent samples., Discussion: The Spanish population can benefit from determining if individuals with high CVR, which is commonly detected in usual clinical practice, will present decreased cognitive performance compared to subjects with lower CVR. This study can affect how to address CVR factors and the design of effective prevention strategies for cognitive deterioration., Trial Registration: Clinicaltrials.gov, NCT03925844., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tapias-Merino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: mHealth technologies could help to improve cardiovascular health; however, their effect on arterial stiffness and hemodynamic parameters has not been explored to date., Objective: To evaluate the effect of a mHealth intervention, at 3 and 12 months, on arterial stiffness and central hemodynamic parameters in a sedentary population with overweight and obesity., Methods: Randomised controlled clinical trial (Evident 3 study). 253 subjects were included: 127 in the intervention group (IG) and 126 in the control group (CG). The IG subjects were briefed on the use of the Evident 3 app and a smart band (Mi Band 2, Xiaomi) for 3 months to promote healthy lifestyles. All measurements were recorded in the baseline visit and at 3 and 12 months. The carotid-femoral pulse wave velocity (cfPWV) and the central hemodynamic parameters were measured using a SphigmoCor System ® device, whereas the brachial-ankle pulse wave velocity (baPWV) and the Cardio Ankle Vascular Index (CAVI) were measured using a VaSera VS-2000 ® device., Results: Of the 253 subjects who attended the initial visit, 237 (93.7%) completed the visit at 3 months of the intervention, and 217 (85.3%) completed the visit at 12 months of the intervention. At 12 months, IG showed a decrease in peripheral augmentation index (PAIx) (-3.60; 95% CI -7.22 to -0.00) and ejection duration (ED) (-0.82; 95% CI -1.36 to -0.27), and an increase in subendocardial viability ratio (SEVR) (5.31; 95% CI 1.18 to 9.44). In CG, cfPWV decreased at 3 months (-0.28 m/s; 95% CI -0.54 to -0.02) and at 12 months (-0.30 m/s, 95% CI -0.54 to -0.05), central diastolic pressure (cDBP) decreased at 12 months (-1.64 mm/Hg; 95% CI -3.19 to -0.10). When comparing the groups we found no differences between any variables analyzed., Conclusions: In sedentary adults with overweight or obesity, the multicomponent intervention (Smartphone app and an activity-tracking band) for 3 months did not modify arterial stiffness or the central hemodynamic parameters, with respect to the control group. However, at 12 months, CG presented a decrease of cfPWV and cDBP, whereas IG showed a decrease of PAIx and ED and an increase of SEVR.

Hypertension mediated organ damage (HMOD) refers to structural or functional changes in arteries or target organs that can be present in long-standing hypertension, but it can be also found in naïve never treated patients. Traditionally, cardiovascular risk is stratified with charts or calculators that tend to underestimate the real cardiovascular risk. The diagnosis of HMOD automatically reclassifies patients to the highest level of cardiovascular risk. Subclinical HMOD can be present already at the diagnosis of hypertension and more than 25% of hypertensives are misclassified with the routine tests recommended by hypertension guidelines. Whether HMOD regression improves cardiovascular outcomes has never been investigated in randomized clinical trials and remains controversial. However, different drugs have been probed with promising results in high cardiovascular risk patients, such as the new antidiabetic or the novel non-steroid mineralocorticoid antagonists. Accordingly, trials have shown that lowering blood pressure reduces cardiovascular events. In this narrative review, we will discuss the role of HMOD in cardiovascular risk stratification, the different types of organ damage, and the evidence available to define whether HMOD can be used as a therapeutic target., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Renal ischemia and reperfusion injury (IRI) is the main cause of acute kidney injury (AKI). AKI induces the development of cardiac hypertrophy (CH) during cardiorenal syndrome (CRS), and cardiomyocyte calcium mishandling though systemic inflammation after 8 days of renal IRI. Klotho has recently been described as an anti-inflammatory component. Given this, Klotho treatment could prevent or attenuate the inflammation, thereby also preventing electrical cardiac outcomes incurred by CRS. The aim of this study was to investigate the therapeutic role of Klotho in CRS after unilateral renal IRI through its anti-inflammatory action., Methods: We examined renal tissue structure and function, intracellular Ca 2+ dynamics in adult ventricular cardiomyocytes and serum cytokine levels from C57BL/6 mice that suffered unilateral renal IRI by occluding the left pedicle for 60 min and reperfusion for 8 days. The animals were treated with recombinant Klotho protein starting from the day of the surgery, then daily for 8 days., Results: After Klotho treatment for 8 days, the left renal tissue remained damaged, however the renal function was restored due to the right kidney tissue preservation. In parallel, Klotho also prevented an increase in serum interleukin (IL-) 6, IL-1β, and tumor necrosis factor alpha (TNF-α) levels. CH and low cell contraction were also prevented, as well as a decrease in systolic Ca 2+ transients and sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2a) activity measured as Ca 2+ transient decay, an increase in spontaneous Ca 2+ release and the incidence of pro-arrhythmic events., Conclusions: The Klotho treatment showed promise, playing an important role in the pathophysiology of CRS. We were unable to observe a total renoprotective role of the compound in the model; in turn, a cardioprotective role of Klotho was demonstrated through the prevention of hypertrophy and normalization of the Ca 2+ cycle dysfunction of cardiomyocytes. We propose that Klotho acts in the cardiorenal syndrome by systematically preventing inflammation and increased FGF23, alleviating cardiac outcomes., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The aim of this study was to analyze the association of physical activity and its intensity with arterial stiffness and vascular aging and differences by sex in a Spanish population with intermediate cardiovascular risk., Methods: Cross-sectional study. A total of 2475 individuals aged 35-75 years participated in the study. Brachial-ankle pulse wave velocity (baPWV) was measured using a VaSera VS-1500 ® device. Based on the age and sex percentile presented by the participants, the latter were classified as follows: those with a percentile above 90 and presenting established cardiovascular disease were classified as early vascular aging (EVA); those with a percentile between 10 and 90 were classified as normal vascular aging (NVA) and those with a percentile below 10 were classified as healthy vascular aging (HVA). Physical activity was analyzed through the short version of the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ)., Results: The mean age of the participants was 61.34 ± 7.70 years, with 61.60% men. Of the total sample, 86% were sedentary (83% men vs 90% women). The total physical activity showed a negative association with baPWV (β = - 0.045; 95% CI - 0.080 to - 0.009). Intense physical activity showed a negative relationship with baPWV (β = - 0.084; 95% CI - 0.136 to - 0.032). The OR of the total physical activity and the intense physical activity carried out by the subjects classified as NVA with respect to those classified as HVA was OR = 0.946; (95% CI 0.898 to 0.997) and OR = 0.903; (95% CI 0.840 to 0.971), and of those classified as EVA it was OR = 0.916; (95% CI 0.852 to 0.986) and OR = 0.905; (95% CI 0.818 to 1.000). No association was found with moderate- or low-intensity physical activity., Conclusions: The results of this study suggest that, when intense physical activity is performed, the probability of presenting vascular aging is lower. In the analysis by sex, this association is only observed in men., (© 2022. The Author(s).)

Purpose: To assess whether subjects with Philadelphia negative myeloproliferative neoplasms (Ph-MPNs) show differences in the presence of vascular, cardiac or renal target organ damage (TOD) and other vascular function parameters as compared to individuals without this condition., Methods: An observational study was conducted. Fifty-seven subjects diagnosed with Ph-MPNs used as cases and 114 subjects without Ph-MPNs as controls. We matched the subjects with and without Ph-MPNs using the propensity scores in a 1:2 ratio using the variables gender, type 2 diabetes mellitus, high blood pressure, hyperlipidaemia and smoking. Vascular, cardiac and renal TOD were established according to the criteria of the European Society of Hypertension and Cardiology guidelines. Arterial stiffness was also assessed using the cardio-ankle vascular index (CAVI)., Results: Mean age was 63.50±11.70 and 62.90±8.32 years in subjects with and without Ph-MPNs, 32 females (56%) in the first group and 62 (54%) in the second. Subjects with Ph-MPNs have a higher percentage of carotid injury than subjects without Ph-MPNs (35.1% vs. 21.1%) and higher albumin/creatinine ratio. In the logistic regression analysis, subjects with Ph-MPNs had an OR=2.382 (IC95% 1.066-5.323) for carotid injury versus those without haematological disease., Conclusions: Subjects with Ph-MPNs have twice the risk of by carotid injury than those without haematological disease., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

The objectives of this study were to analyse the capacity of different anthropometric indices to predict vascular ageing and this association in Spanish adult population without cardiovascular disease. A total of 501 individuals without cardiovascular disease residing in the capital of Salamanca (Spain) were selected (mean age: 55.9 years, 50.3% women), through stratified random sampling by age and sex. Starting from anthropometric measurements such as weight, height, and waist circumference, hip circumference, or biochemical parameters, we could estimate different indices that reflected general obesity, abdominal obesity, and body fat distribution. Arterial stiffness was evaluated by measuring carotid-femoral pulse wave velocity (cf-PWV) using a SphygmoCor ® device. Vascular ageing was defined in three steps: Step 1: the participants with vascular injury were classified as early vascular ageing (EVA); Step 2: classification of the participants using the 10 and 90 percentiles of cf-PWV in the study population by age and sex in EVA, healthy vascular ageing (HVA) and normal vascular ageing (NVA); Step 3: re-classification of participants with arterial hypertension or type 2 diabetes mellitus included in HVA as NVA. The total prevalence of HVA and EVA was 8.4% and 21.4%, respectively. All the analysed anthropometric indices, except waist/hip ratio (WHpR), were associated with vascular ageing. Thus, as the values of the different anthropometric indices increase, the probability of being classified with NVA and as EVA increases. The capacity of the anthropometric indices to identify people with HVA showed values of area under the curve (AUC) ≥ 0.60. The capacity to identify people with EVA, in total, showed values of AUC between 0.55 and 0.60. In conclusion, as the values of the anthropometric indices increased, the probability that the subjects presented EVA increased. However, the relationship of the new anthropometric indices with vascular ageing was not stronger than that of traditional parameters. Therefore, BMI and WC can be considered to be the most useful indices in clinical practice to identify people with vascular ageing in the general population.

Biomarkers of mineral bone disorders (MBD) including phosphorus, fibroblast growth factor (FGF)-23 and Klotho are strongly altered in patients with acute kidney injury (AKI) who have high cardiac outcomes and mortality rates. However, the crosslink between MBD and cardiac damage after an AKI episode still remains unclear. We tested MBD and cardiac biomarkers in an experimental AKI model after 24 or 72 hours of folic acid injection and we analyzed structural cardiac remodeling, intracellular calcium (Ca 2+ ) dynamics in cardiomyocytes and cardiac rhythm. AKI mice presented high levels of FGF-23, phosphorus and cardiac troponin T and exhibited a cardiac hypertrophy phenotype accompanied by an increase in systolic Ca 2+ release 24 hours after AKI. Ca 2+ transients and contractile dysfunction were reduced 72 hours after AKI while diastolic sarcoplasmic reticulum Ca 2+ leak, pro-arrhythmogenic Ca 2+ events and ventricular arrhythmias were increased. These cardiac events were linked to the activation of the calcium/calmodulin-dependent kinase II pathway through the increased phosphorylation of ryanodine receptors and phospholamban specific sites after AKI. Cardiac hypertrophy and the altered intracellular Ca 2+ dynamics were prevented in transgenic mice overexpressing Klotho after AKI induction. In a translational retrospective longitudinal clinical study, we determined that combining FGF-23 and phosphorus with cardiac troponin T levels achieved a better prediction of mortality in AKI patients at hospital admission. Thus, monitoring MBD and cardiac damage biomarkers could be crucial to prevent mortality in AKI patients. In this setting, Klotho might be considered as a new cardioprotective therapeutic tool to prevent deleterious cardiac events in AKI conditions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sedentary behaviour is associated with a greater predisposition to developing cardiovascular diseases. The aim of the study was to analyse the relationship between sedentary time and early vascular ageing. A total of 501 participants (49.70% men) were recruited through random sampling stratified by age group and sex. Vascular ageing was evaluated considering three criteria: (1) the vascular ageing index (VAI); (2) the carotid−femoral pulse wave velocity (cfPWV) 10th and 90th percentiles of the reference values in the European population by age; and (3) the Framingham’s heart age. The carotid intima−media thickness was measured using a Sonosite Micromaxx ultrasound, the presence of peripheral artery disease was assessed by calculating the ankle−brachial index using a VaSera VS-1500, and the cfPWV was measured with a SphygmoCor® device. Weekly sedentary hours were evaluated through a sitting time questionnaire. The average age of the population was 55.90 ± 14.24 years. The men spent more hours sitting per week (47.6 ± 16.6 vs. 36.8 ± 17.3 h/W), at work (16.7 ± 16.2 vs. 9.73 ± 14.9 h/W), and watching TV (21.6 ± 12.5 vs. 18.7 ± 11.9 h/W). In the logistic regression analysis, the individuals with early vascular aging (EVA), with respect to those with healthy vascular aging (HVA), spent more hours sitting per week (OR = 1.03 vs. OR = 1.02; p < 0.05) and watching TV (OR = 1.03 vs. OR = 1.03; p < 0.05), using the criteria of the European guideline and VAI, and more hours sitting when commuting (OR = 1.04; p < 0.05), using Framingham’s heart age to define EVA. The results of this study indicate that sedentary time is associated with early vascular ageing. Therefore, reducing sedentary time would improve vascular health.

Background: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown., Methods: We examined intracellular Ca 2+ dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days following unilateral renal I/R., Results: After 7 days of I/R, the cell contraction was significantly lower in cardiomyocytes compared to sham-treated mice. It was accompanied by a significant decrease in both systolic Ca 2+ transients and sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA 2a ) activity measured as Ca 2+ transients decay. Moreover, the incidence of pro-arrhythmic events, measured as the number of Ca 2+ sparks, waves or automatic Ca 2+ transients, was greater in cardiomyocytes from mice 7 days after I/R than from sham-treated mice. Ca 2+ mishandling related to systolic Ca 2+ transients and contraction were recovered to sham values 15 days after I/R, but Ca 2+ sparks frequency and arrhythmic events remained elevated., Conclusions: Renal I/R injury causes a cardiomyocyte Ca 2+ cycle dysfunction at medium (contraction-relaxation dysfunction) and long term (Ca 2+ leak), after 7 and 15 days of renal reperfusion, respectively.

Introduction: The aim of this work was to analyse the association of the retinal arteriolar calibre and the arteriole/venule index (AV index) with vascular ageing in a general population without previous cardiovascular disease., Materials and Methods: Descriptive cross-sectional study. A total of 482 individuals without cardiovascular disease (mean age: 55.6 ± 14.2 years) were selected by random sampling, stratified by age and sex. The retinal arteriolar calibre was measured using digital fundus images of the back of the eye captured with a validated, semiautomatized and computer-assisted software (Index calculator). Vascular ageing was defined using three criteria based on the values of: (1) Carotid-femoral Pulse Wave Velocity (cfPWV), (2) Brachial-ankle Pulse Wave Velocity (baPWV) and (3) Carotid Intima-Media Thickness., Results: The AV index and arteriolar calibre show a negative correlation with age, arterial pressure, cardiovascular risk and parameters of vascular structure and function (p < 0.001 in all cases). We found lower mean values of the AV index and arteriolar calibre in the individuals with early vascular ageing compared to those with healthy vascular ageing. AV index was negatively correlated with cfPWV ((β=-2.9; 95% CI (-4.7; -1.1)), baPWV ((β=-3.2; 95% CI (-5.4; -0.9)) and vascular ageing index ((β=-1.7; 95% CI (-2.7; -0.7)). Arteriolar calibre showed a negative correlation with baPWV (β=-0.1; 95% CI (-0.2; -0.1)). In the logistic regression analysis, lower values of AV index ((OR=0.01; 95% CI (0.01-0.10), OR=0.03; 95% CI (0.01-0.11) and OR=0.09; 95% CI (0.01-0.67)) were associated with EVA defined with cfPWV, baPWV and vascular ageing index respectively, and lower values of arteriolar calibre ((OR=0.71; 95% CI (0.55-0.91)) were associated with EVA defined with vascular ageing index., Conclusions: Lower values of AV index and retinal arteriolar calibre were associated with vascular ageing in a general Spanish population without previous cardiovascular disease., (© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown., Methods: We carried out a translational approach to study the relationship between the FGF23-Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels., Results: Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K + ) current (I tof ), caused by the downregulation of K + channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced I tof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes., Conclusion: The FGF23-Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD., (© 2022. The Author(s).)

A balanced diet can help in the prevention of chronic diseases. The aim of this study was to evaluate the effect of an mHealth intervention on the distribution of macronutrients and the intake of food groups. A total of 650 participants were included in this multi-center, clinical, randomized, controlled trial (Evident 3 study). All participants were given brief advice about diet and exercise. The intervention group received, in addition, an app (Evident 3) for the self-recording of their diet and an activity tracker wristband for 3 months. Follow-up visits were performed at 3 and 12 months to collect the diet composition using the Food Frequency Questionnaire. There were decreases in the intake of total calories, fat, protein and carbohydrates in both groups throughout the study, without significant differences between them. The intervention group reduced the intake of cholesterol (-30.8; 95% CI -59.9, -1.7) and full-fat dairies (-23.3; 95% CI -42.8, -3.8) and increased the intake of wholemeal bread (3.3; 95% CI -6.7, 13.3) and whole-grain cereals (3.4; 95% CI -6.8, 13.7) with respect to the control group. No differences were found in the rest of the nutritional parameters. The brief advice is useful to promote a healthier diet, and the app can be a support tool to obtain changes in relevant foods, such as integral foods, and the intake of cholesterol. Trial registration: ClinicalTrials.gov with identifier NCT03175614.

The aim of this study was to analyse the association of diet with arterial stiffness and vascular ageing in a Caucasian population with intermediate cardiovascular risk. We recruited 2475 individuals aged 35-75 years with intermediate cardiovascular risk. Brachial-ankle pulse wave velocity (baPWV) was measured using a VaSera VS-1500 ® device. Vascular ageing was defined in two steps. Step 1: The 20 individuals who presented kidney disease, peripheral arterial disease, or heart failure were classified as early vascular ageing (EVA). Step 2: The individuals with percentiles by age and sex above the 90th percentile of baPWV among the participants of this study were classified as EVA, and the rest of the individuals were classified as non-EVA. The diet of the participants was analysed with two questionnaires: (1) the diet quality index (DQI) questionnaire and (2) the Mediterranean diet (MD) adherence questionnaire. The mean age of the sample was 61.34 ± 7.70 years, and 61.60% were men. Adherence to the MD was 53.30%. The DQI was 54.90%. Of the entire sample, 10.70% (11.15% of the men and 9.95% of the women) were EVA. In the multiple linear regression analysis, for each additional point in the DQI questionnaire, there was a decrease of -0.081 (95%CI (confidence intervals) -0.105--0.028) in baPWV; in the MD adherence questionnaire, there was a decrease of -0.052 (95%CI -0141--0.008). When performing the analysis, separated by sex, the association remained significant in men but not in women. In the logistic regression analysis, there was an increase in MD adherence and a decrease in the probability of presenting EVA, both with the DQI questionnaire (OR (odds ratio) = 0.65; 95%CI 0.50-0.84) and with the MD adherence questionnaire (OR = 0.75; 95%CI 0.58-0.97). In the analysis by sex, the association was only maintained in men (with DQI, OR = 0.54; 95%CI 0.37-0.56) (with MD, OR = 0.72; 95%CI 0.52-0.99). The results of this study suggest that a greater score in the DQI and MD adherence questionnaires is associated with lower arterial stiffness and a lower probability of presenting EVA. In the analysis by sex, this association is only observed in men.

Aims: The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH)., Methods and Results: Ambulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24 h systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24 h PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway., Conclusion: We propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The data on the relationship between insulin resistance and vascular ageing are limited. The aim of this study was to explore the association of different indices of insulin resistance with vascular ageing in an adult Caucasian population without cardiovascular disease. We selected 501 individuals without cardiovascular disease (mean age: 55.9 years, 50.3% women) through random sampling stratified by sex and age. Arterial stiffness was evaluated by measuring the carotid-to-femoral pulse wave velocity (cfPWV) and brachial-to-ankle pulse wave velocity (baPWV). The participants were classified into three groups according to the degree of vascular ageing: early vascular ageing (EVA), normal vascular ageing (NVA) and healthy vascular ageing (HVA). Insulin resistance was evaluated with the homeostatic model assessment of insulin resistance (HOMA-IR) and another five indices. The prevalence of HVA and EVA was 8.4% and 21.4%, respectively, when using cfPWV, and 7.4% and 19.2%, respectively, when using baPWV. The deterioration of vascular ageing, with both measurements, presented as an increase in all the analysed indices of insulin resistance. In the multiple regression analysis and logistic regression analysis, the indices of insulin resistance showed a positive association with cfPWV and baPWV and with EVA.

Introduction: Little is known about the relationship between arterial stiffness and cardiovascular target organ damage (TOD) in the general population. The aim was to analyse the relationship between different measurements of arterial stiffness and TOD, in a general Spanish population without a history of cardiovascular event., Materials and Methods: Transversal descriptive study. Through stratified random sampling, a total of 501 individuals were included. Carotid-femoral pulse wave velocity (cf-PWV) was measured using a SphygmoCor System ® , the cardio-ankle vascular index (CAVI) was determined with aVasera VS-1500 ® and brachial-ankle pulse wave velocity (ba-PWV)was calculated through a validated equation., Results: The average age was 55.84 ± 14.26.The percentage of vascular TOD, left ventricular hypertrophy (LVH) and renal TOD was higher in men ( p  < .001). A positive correlation was obtained between carotid intima-media thickness (c-IMT) and the measurements of vascular function. In the model 1 of the logistic regression analysis, cf-PWV was associated with vascular TOD (OR = 1.15, p  = .040), ba-PWV was associated with vascular TOD (OR = 1.20, p  = .010) and LVH (OR = 1.12, p  = .047)., Conclusions: The different measurements of arterial stiffness are highly associated with each other. Moreover, cf-PWV and ba-PWV were associated with vascular TOD, and ba-PWV with LVH, although they disappear when adjusting for cardiovascular risk factors. Key Messages There is a strong correlation between the different measurements of vascular structure and function. Carotid-femoral and brachial-ankle pulse wave velocity were positively associated with vascular target organ damage, the latter was also positively associated with left ventricular hypertrophy. This associations disappear when adjusting for cardiovascular risk factors.

Background: In most trials and systematic reviews that evaluate exercise-based interventions in reducing depressive symptoms, it is difficult to separate treatment from prevention., Aims: To evaluate the effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression., Method: We searched PubMed, PsycINFO, Embase, WOS, SPORTDiscus, CENTRAL, OpenGrey and other sources up to 25 May 2020. We selected randomised controlled trials (RCTs) that compared exclusively exercise-based interventions with control groups, enrolling participants without clinical depression, as measured using validated instruments, and whose outcome was reduction of depressive symptoms and/or incidence of new cases of people with depression. Pooled standardised mean differences (SMDs) were calculated using random-effect models (registration at PROSPERO: CRD42017055726)., Results: A total of 14 RCTs (18 comparisons) evaluated 1737 adults without clinical depression from eight countries and four continents. The pooled SMD was -0.34 (95% CI -0.51 to -0.17; P < 0.001) and sensitivity analyses confirmed the robustness of this result. We found no statistical evidence of publication bias and heterogeneity was moderate (I2 = 54%; 95% CI 22-73%). Only two RCTs had an overall low risk of bias and three had long-term follow-up. Multivariate meta-regression found that a larger sample size, country (Asia) and selective prevention (i.e. people exposed to risk factors for depression) were associated with lower effectiveness, although only sample size remained significant when adjustment for multiple tests was considered. According to the Grading of Recommendations Assessment, Development and Evaluation tool, the quality of evidence was low., Conclusions: Exercise-based interventions have a small effect on the reduction of depressive symptoms in people without clinical depression. It could be an alternative to or complement psychological programmes, although further higher-quality trials with larger samples and long-term follow-up are needed.