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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).)

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).)

Background: Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care., Methods: Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months., Results: With a willingness-to-pay threshold of €10,000 (£8568) the probability of cost-effectiveness oscillated from 83% (societal perspective) to 89% (health perspective). If the threshold was increased to €30,000 (£25,704), the probability of being considered cost-effective was 94% (societal perspective) and 96%, respectively (health perspective). The sensitivity analysis confirmed these results., Conclusions: Compared with usual care, an intervention based on personal predictors of risk of depression implemented by GPs is a cost-effective strategy to prevent depression. This type of personalized intervention in primary care should be further developed and evaluated., Trial Registration: ClinicalTrials.gov, NCT01151982. Registered on June 29, 2010.

Background: We analyzed the associations between diabetes and cognitive impairment (CI) and dependence in a population of patients 65 years or older., Methods: Cross-sectional study. We randomly selected 311 participants over the age of 65 living in an urban area of Spain. The mean age of the cohort was 75.89 ± 7.12 years, and 69 of the individuals (22.2%) had diabetes. Two questionnaires were used to assess cognitive performance (MMSE and Seven Minute Screen Test), and two assessments were used to evaluate patient dependence (Barthel Index and Lawton-Brody Index). Clinical information and sociodemographic data were also gathered., Results: Nearly one quarter of patients with diabetes (21.7%) lived alone. Diabetic patients were more sedentary (p = .033) than non-diabetic patients. Roughly one sixth (15.3%) of the diabetics and 10.1% of the non-diabetics were depressed (p = .332). CI was present in 26.1% of the diabetics and 14.5% of non-diabetics (p = .029). Diabetic patients had a MMSE score that was significantly worse than non-diabetics (24.88 ± 4.74 vs 26.05 ± 4.03; p <.05), but no differences were found in the Seven Minute Screen Test. Logistic regressions revealed that the presence of diabetes was independently associated with CI (adjusted for age, gender, years of education, sedentary lifestyle, body mass index, diastolic blood pressure, cholesterol, and depression (OR = 2.940, p = .013). Patients with diabetes showed greater dependence, as measured by the Barthel Index (p = .03) and Lawton-Brody Index (p <.01). Nevertheless, when dependence (dependence or not dependence for each questionnaire) used as a dependent variable in the logistic regression analyses, no significant association with diabetes was found, after adjusting for confounding variables., Conclusions: Diabetic patients over the age of 65 are more likely to present CI but not dependence. These findings support the need to include both a functional and cognitive assessment as necessary components in a standard evaluation in both clinical guides and randomized trials of therapeutic interventions in patients with diabetes.

Background: The 'predictD algorithm' provides an estimate of the level and profile of risk of the onset of major depression in primary care attendees. This gives us the opportunity to develop interventions to prevent depression in a personalized way. We aim to evaluate the effectiveness, cost-effectiveness and cost-utility of a new intervention, personalized and implemented by family physicians (FPs), to prevent the onset of episodes of major depression., Methods/design: This is a multicenter randomized controlled trial (RCT), with cluster assignment by health center and two parallel arms. Two interventions will be applied by FPs, usual care versus the new intervention predictD-CCRT. The latter has four components: a training workshop for FPs; communicating the level and profile of risk of depression; building up a tailored bio-psycho-family-social intervention by FPs to prevent depression; offering a booklet to prevent depression; and activating and empowering patients. We will recruit a systematic random sample of 3286 non-depressed adult patients (1643 in each trial arm), nested in 140 FPs and 70 health centers from 7 Spanish cities. All patients will be evaluated at baseline, 6, 12 and 18 months. The level and profile of risk of depression will be communicated to patients by the FPs in the intervention practices at baseline, 6 and 12 months. Our primary outcome will be the cumulative incidence of major depression (measured by CIDI each 6 months) over 18 months of follow-up. Secondary outcomes will be health-related quality of life (SF-12 and EuroQol), and measurements of cost-effectiveness and cost-utility. The inferences will be made at patient level. We shall undertake an intention-to-treat effectiveness analysis and will handle missing data using multiple imputations. We will perform multi-level logistic regressions and will adjust for the probability of the onset of major depression at 12 months measured at baseline as well as for unbalanced variables if appropriate. The economic evaluation will be approached from two perspectives, societal and health system., Discussion: To our knowledge, this will be the first RCT of universal primary prevention for depression in adults and the first to test a personalized intervention implemented by FPs. We discuss possible biases as well as other limitations., Trial Registration: ClinicalTrials.gov identifier: NCT01151982.

Background: We investigated the association between heart rate and its variability with the parameters that assess vascular, renal and cardiac target organ damage., Methods: A cross-sectional study was performed including a consecutive sample of 360 hypertensive patients without heart rate lowering drugs (aged 56 ± 11 years, 64.2% male). Heart rate (HR) and its standard deviation (HRV) in clinical and 24-hour ambulatory monitoring were evaluated. Renal damage was assessed by glomerular filtration rate and albumin/creatinine ratio; vascular damage by carotid intima-media thickness and ankle/brachial index; and cardiac damage by the Cornell voltage-duration product and left ventricular mass index., Results: There was a positive correlation between ambulatory, but not clinical, heart rate and its standard deviation with glomerular filtration rate, and a negative correlation with carotid intima-media thickness, and night/day ratio of systolic and diastolic blood pressure. There was no correlation with albumin/creatinine ratio, ankle/brachial index, Cornell voltage-duration product or left ventricular mass index. In the multiple linear regression analysis, after adjusting for age, the association of glomerular filtration rate and intima-media thickness with ambulatory heart rate and its standard deviation was lost. According to the logistic regression analysis, the predictors of any target organ damage were age (OR = 1.034 and 1.033) and night/day systolic blood pressure ratio (OR = 1.425 and 1.512). Neither 24 HR nor 24 HRV reached statistical significance., Conclusions: High ambulatory heart rate and its variability, but not clinical HR, are associated with decreased carotid intima-media thickness and a higher glomerular filtration rate, although this is lost after adjusting for age., Trial Registration: ClinicalTrials.gov: NCT01325064.

Background: To analyze the relationship of cocoa intake to central and peripheral blood pressure, arterial stiffness, and carotid intima-media thickness in subjects with some cardiovascular risk factor., Design: A cross-sectional study of 351 subjects (mean age 54.76 years, 62.4% males)., Measurements: Intake of cocoa and other foods using a food frequency questionnaire, central and peripheral (ambulatory and office) blood pressure, central and peripheral augmentation index, pulse wave velocity, ambulatory arterial stiffness index, carotid intima-media thickness, and ankle-brachial index., Results: Higher pulse wave velocity and greater cardiovascular risk were found in non-cocoa consumers as compared to high consumers (p < 0.05). In a multivariate analysis, these differences disappeared after adjusting for age, gender, the presence of diabetes, systolic blood pressure and antihypertensive and lipid-lowering drug use. All other arterial stiffness measures (central and peripheral augmentation index, ambulatory arterial stiffness index, ankle-brachial index, and carotid intima-media thickness) showed no differences between the different consumption groups., Conclusions: In subjects with some cardiovascular risk factors, cocoa consumption does not imply improvement in the arterial stiffness values., Trial Registration: Clinical Trials.gov Identifier: NCT01325064.

Background: The present study was designed to evaluate which arterial stiffness parameter - AASI or the home arterial stiffness index (HASI) - correlates best with vascular, cardiac and renal damage in hypertensive individuals., Methods: A cross-sectional study was carried out involving 258 hypertensive patients. AASI and HASI were defined as the 1-regression slope of diastolic over systolic blood pressure readings obtained from 24-hour recordings and home blood pressure over 6 days. Renal damage was evaluated by glomerular filtration rate (GFR) and microalbuminuria; vascular damage by carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI); and left ventricular hypertrophy by the Cornell voltage-duration product (VDP) and the Novacode index., Results: AASI and HASI were not correlated with microalbuminuria, however AASI and HASI- blood pressure variability ratio (BPVR) showed negative correlation with GRF. The Cornell PDV was positively correlated with AASI- BPVR-Sleep (r = 0.15, p < 0.05) and the left ventricular mass index with HASI-BPVR (r = 0.19, p < 0.01). Carotid IMT and PWV were positively correlated with all the parameters except the HASI, while ABI was negatively correlated with AASI and Awake-AASI. After adjusting for age, gender and 24 hours heart rate, statistical significance remains of the IMT with AASI, Awake AASI and AASI-BPVR. PWV with the AASI, Awake-AASI and Sleep-AASI. ABI with AASI and Awake-AASI. Odd Ratio to presence target organ damage was for AASI: 10.47(IC95% 1.29 to 65.34), Awake-AASI: 8.85(IC95% 1.10 to 71.04), Sleep-AASI: 2.19(IC95% 1.10 to 4.38) and AASI-BPVR-night: 4.09 (IC95% 1.12 to 14.92)., Conclusions: After adjusting for age, gender and 24-hour heart, the variables that best associated with the variability of IMT, PWV and ABI were AASI and Awake-AASI, and with GFR was HASI-BPVR.

Background: Few data are available on the prevalence of cognitive impairment (CI) in Spain, and the existing information shows important variations depending on the geographical setting and the methodology employed. The aim of this study was to determine the prevalence of CI in individuals aged over 65 in an urban area, and to analyze its associated risk factors., Design: A descriptive, cross-sectional, home questionnaire-based study;, Setting: Populational, urban setting., Participants: The reference population comprised over-65s living in the city of Salamanca (Spain) in 2009. Randomized sampling stratified according to health district was carried out, and a total of 480 people were selected. In all, 327 patients were interviewed (68.10%), with a mean age of 76.35 years (SD: 7.33). Women accounted for 64.5% of the total., Measurements: A home health questionnaire was used to obtain the following data: age, sex, educational level, family structure, morbidity and functionality. All participants completed a neuropsychological test battery. The prevalence data were compared with those of the European population, with direct adjustment for age and sex. Diagnoses were divided into three general categories: normal cognitive function, cognitive impairment - no dementia (CIND), and dementia., Results: The prevalence of CI among these over-65s was 19% (14.7% CIND and 4.3% dementia). The age-and sex-adjusted global prevalence of CI was 14.9%. CI increased with age (p < 0.001) and decreased with increasing educational level (p < 0.001). Significant risk factors were found with the multivariate analyses: age (OR = 1.08, 95%CI: 1.03-1.12), anxiety-depression (OR = 3.47, 95%CI: 1.61-7.51) and diabetes (OR = 2.07, 95%CI: 1.02-4.18). In turn, years of education was found to be a protective factor (OR = 0.79, 95%CI: 0.70-0.90). Although CI was more frequent among women and in people living without a partner, these characteristics were not significantly associated with CI risk., Conclusions: The observed raw prevalence of CI was 19% (14.9% after adjusting for age and sex). Older age and the presence of diabetes and anxiety-depression increased the risk of CI, while higher educational level reduced the risk.

Background: Studies centered on the detection of cognitive impairment and its relationship to cardiovascular risk factors in elderly people have gained special relevance in recent years. Knowledge of the cardiovascular risk factors that may be associated to cognitive impairment could be very useful for introducing treatments in early stages - thereby possibly contributing to improve patient quality of life.The present study explores cognitive performance in people over 65 years of age in Salamanca (Spain), with special emphasis on the identification of early symptoms of cognitive impairment, with the purpose of detecting mild cognitive impairment and of studying the relationships between this clinical situation and cardiovascular risk factors., Methods/design: A longitudinal study is contemplated. The reference population will consist of 420 people over 65 years of age enrolled through randomized sampling stratified by healthcare area, and who previously participated in another study., Measurement: a) Sociodemographic variables; b) Cardiovascular risk factors; c) Comorbidity; d) Functional level for daily life activities; and e) Study of higher cognitive functions based on a neuropsychological battery especially adapted to the evaluation of elderly people., Discussion: We hope that this study will afford objective information on the representative prevalence of cognitive impairment in the population over 65 years of age in Salamanca. We also hope to obtain data on the relationship between cognitive impairment and cardiovascular risk factors in this specific population group. Based on the results obtained, we also will be able to establish the usefulness of some of the screening tests applied during the study, such as the Mini-Mental State Examination and the 7 Minute Screen test., Trial Registration: ClinicalTrials.gov: NCT01327196.

Background: There are caregivers who see their quality of life (QoL) impaired due to the demands of their caregiving tasks, while others manage to adapt and overcome the crises successfully. The influence of the family function in the main caregiver's situation has not been the subject of much evaluation. The aim of this study is to analyse the relationship between the functionality of the family and the QoL of caregivers of dependent relatives., Methods: We conducted a cross-sectional study including 153 caregivers., Setting: Two health centers in the city of Salamanca(Spain). Caregiver variables analysed: demographic characteristics, care recipient features; family functionality (Family APGAR-Q) and QoL (Ruiz-Baca-Q) perceived by the caregiver. Five multiple regressions are performed considering global QoL and each of the four QoL dimensions as dependent variables. The Canonical Correspondence Analysis (CCA) was used to study the influence of the family function questionnaire on QoL., Results: Family function is the only one of the variables evaluated that presented an association both with global QoL and with each of the four individual dimensions (p<0.05). Using the CCA, we found that the physical and mental well-being dimensions are the ones which present a closer relationship with family functionality, while social support is the quality dimension that is least influenced by the Family APGAR-Q., Conclusion: We find an association between family functionality and the caregiver's QoL. This relation holds for both the global measure of QoL and each of its four individual dimensions., (© 2011 Rodríguez-Sánchez et al; licensee BioMed Central Ltd.)

Background: We examined the relationship between the intima-media thickness of the common carotid artery (CCA-IMT) and arterial stiffness, assessed by pulse wave velocity (PWV), the ambulatory arterial stiffness index (AASI) and the augmentation index (AIx) in subjects with and without type 2 diabetes., Methods: A case-series study was made in 366 patients (105 diabetics and 261-non-diabetics). Ambulatory blood pressure monitoring was performed on a day of standard activity with the SpaceLabs 90207 system. AASI was calculated as "1-slope" from the within-person regression of diastolic-on-systolic ambulatory blood pressure readings. PWV and AIx were measured with the SphygmoCor system, and a Sonosite Micromax ultrasound unit was used for automatic measurements of CCA-IMT., Results: PWV, AASI and CCA-IMT were found to be greater in diabetic patients, while no differences in AIx were observed between the two groups. CCA-IMT was independently correlated to the three measures of arterial stiffness in both groups. We found an increase in CCA-IMT of 0.40, 0.24 and 0.36 mm in diabetics, and of 0.48, 0.17 and 0.55 mm in non-diabetics for each unit increase in AASI, AIx and PWV. The variability of CCA-IMT was explained mainly by AASI, AIx and gender in diabetic patients, and by age, gender, AASI and PWV in non-diabetic patients., Conclusions: CCA-IMT showed a positive correlation to PWV, AASI and AIx in subjects with and without type 2 diabetes. However, when adjusting for age, gender and heart rate, the association to PWV was lost in diabetic patients, in the same way as the association to Alx in non-diabetic patients. The present study demonstrates that the three measures taken to assess arterial stiffness in clinical practice are not interchangeable, nor do they behave equally in all subjects.

Background: Although Primary Health Care (PHC) Teams are used to deal with prevention and treatment of sanitary problems in adults with chronic diseases, they usually have a lack of experience in development of psychotherapeutic interventions. However, these interventions are the ones that achieve better results to reduce symptomatology and improve emotional state of caregivers.The study aims to evaluate the effectiveness of an intervention of psychotherapy in improving the mental health and Quality of life of caregivers. This intervention is based on theoretical approaches to care adjusted to cognitive theory, in order to be applied in primary health care centres., Methods/design: This is multicentre clinical trials study, randomized in two parallel groups, carry out in two PHC, Study population: 150 caregivers will be included by consecutive sampling and they will be randomized the half to experimental group and the other half to control group. They provide mostly all the assistance to care-dependent familiars receiving attention in PHC Centers., Measurements: Each caregiver will be evaluated on a personal interview. The caregivers' assessment protocol: 1) Assessment of different socio-demographic related to care, and caregiver's personal situation. 2)Care-dependent individuals will also be assessed by Barthel Index and Pfeiffer Questionnaire (SPMSQ). 3)Change in caregivers will be the principal measure: family function (Family APGAR Questionnaire), burden short questionnaire (Short Zarit Burden Interview), quality of life (Ruiz & Baca: 1993 Questionnaire), the Duke-UNK Functional Social Support Questionnaire, the General Health Questionnaire-12, and changes in Dysfunctional Thoughts about caring. 4) Intervention implementation measures will also be assessed., Intervention: A psychotherapeutic intervention will be 8 sessions of 90 minutes in groups. This intervention has been initially developed for family caregivers of patients with dementia., Discussion: Psychotherapeutic interventions have been proved to obtain better results to reduce symptomatology and improve emotional state of caregivers. Moreover, this intervention has been proved to be effective in a different setting other than PHC, and was developed by professionals of Mental Health. If we found that this intervention is effective in PHC and with our professionals, it would be an important instrument to offer to caregivers of care-dependent patients., Trial Registration: ClinicalTrials.gov Identifier NCT01177696.

Background: Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome., Design: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up., Setting: The study will be carried out in the urban primary care setting., Study Population: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included., Measurements: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs., Discussion: The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus.