Adherence to Supervised and Unsupervised Exercise Programmes in Ageing Population with Intermittent Claudication: A Randomized Controlled Trial.

Background: Intermittent Claudication symptomatic peripheral arterial disease (ICSPAD) is associated with reduced mobility, functional capacity, and quality of life. Physical exercise is an effective non-pharmacological intervention for the management of ICSPAD. Adherence to exercise programs is challenging, due to the nature of the disease and the complex comorbidities associated with it. This study aimed to determine adherence to three supervised physical exercise programs (a walking intervention, strength intervention, and concurrent intervention) and an unsupervised exercise program (standard advice) in individuals with ICSPAD. Methods: In this clinical trial, 122 patients were divided into four groups based on the type of exercise program they followed: standard advice, walking intervention, strength intervention, and concurrent intervention. Results: The results revealed that while the demographic characteristics were similar, the strength intervention group had a younger mean age, and the walking group had a higher prevalence of hypertension and increased usage of anti-hypertensive drugs. Adherence to physical exercise and pedometer wearing was highest in the standard advice group. Logistic regression analysis showed lower odds of adherence to exercise and pedometer wearing in the intervention groups compared to the standard advice group. Adherence did not significantly vary across ankle-brachial index categories. Furthermore, there was no significant difference in adherence between the severity levels of intermittent claudication, though mild cases tended to exhibit higher adherence. Conclusions: The results show that the standard advice from healthcare professionals positively influences treatment adherence.

Genetic Variants at the 9p21.3 Locus Are Associated with Risk for Non-Compressible Artery Disease: Results from the ARTPER Study.

Peripheral artery disease (PAD) and non-compressible artery disease (NCAD) constitute predictors of subclinical atherosclerosis easily assessed through the ankle brachial index (ABI). Although both diseases show substantial genetic influences, few genetic association studies have focused on the ABI and PAD, and none have focused on NCAD. To overcome these limitations, we assessed the role of several candidate genes on the ABI, both in its continuous distribution and in the clinical manifestations associated to its extreme values: PAD and NCAD. We examined 13 candidate genomic regions in 1606 participants from the ARTPER study, a prospective population-based cohort, with the ABI assessed through ultrasonography. Association analyses were conducted independently for individuals with PAD (ABI < 0.9) or with NCAD (ABI > 1.4) vs. healthy participants. After including potential covariates and correction for multiple testing, minor alleles in the genetic markers rs10757278 and rs1333049, both in the 9p21.3 region, were significantly associated with a decreased risk of NCAD. Associations with the ABI showed limited support to these results. No significant associations were detected for PAD. The locus 9p21.3 constitutes the first genetic locus associated with NCAD, an assessment of subclinical atherosclerosis feasible for implementation in primary healthcare settings that has been systematically neglected from genetic studies.

Automated Systems for Calculating Arteriovenous Ratio in Retinographies: A Scoping Review.

There is evidence of an association between hypertension and retinal arteriolar narrowing. Manual measurement of retinal vessels comes with additional variability, which can be eliminated using automated software. This scoping review aims to summarize research on automated retinal vessel analysis systems. Searches were performed on Medline, Scopus, and Cochrane to find studies examining automated systems for the diagnosis of retinal vascular alterations caused by hypertension using the following keywords: diagnosis; diagnostic screening programs; image processing, computer-assisted; artificial intelligence; electronic data processing; hypertensive retinopathy; hypertension; retinal vessels; arteriovenous ratio and retinal image analysis. The searches generated 433 articles. Of these, 25 articles published from 2010 to 2022 were included in the review. The retinographies analyzed were extracted from international databases and real scenarios. Automated systems to detect alterations in the retinal vasculature are being introduced into clinical practice for diagnosis in ophthalmology and other medical specialties due to the association of such changes with various diseases. These systems make the classification of hypertensive retinopathy and cardiovascular risk more reliable. They also make it possible for diagnosis to be performed in primary care, thus optimizing ophthalmological visits.

[Evolution of the prevalence of peripheral artery disease in clinical practice: A descriptive population study with real databases (SIDIAP-CMBD)]. / Evolución de la prevalencia de arteriopatía periférica en la práctica clínica: Estudio descriptivo poblacional con bases de datos reales (SIDIAP-CMBD).

OBJECTIVE: To evaluate, with real world data (SIDIAP and CMBD), the evolution of the prevalence of peripheral arterial disease (PAD) in the Catalan population and the cardiovascular risk factors present in people with this pathology. DESIGN: Longitudinal descriptive population study. SITE: Primary health care. PARTICIPANTS: Patients listed in SIDIAP and CMBD with a diagnosis of peripheral artery disease between 2008 and 2018 ≥ 35 years, as well as those without a diagnosis, but with an ABI < 0.9 in SIDIAP. INTERVENTIONS AND MAIN MEASUREMENTS: Main variable AP (ICD-9, ICD-10). Sociodemographic data, risk factors and cardiovascular disease, drug use and prevalent cardiovascular events at the time of diagnosis. RESULTS: 141,520 patients were studied. 75% had hypertension, 58% were smokers or former smokers, and 23% had a myocardial infarction. The global prevalence increased from 1.15% in 2008 to 3.10% in 2018. The prevalence of PAD increased with age, with a moderate increase at younger ages, and more pronounced in > 55 years, exceeding 10% in > 85 years. CONCLUSION: This is a population study where it is observed that the evolution of the prevalence of peripheral artery disease has presented a constant increase during the years 2008-2018, being higher in men, especially from 55 years of age. Studies with large databases can facilitate the design and implementation of new policies in national health systems.

Supervised physical activity in patients with symptomatic peripheral arterial disease: protocol for a randomized clinical trial (ARTPERfit Study).

INTRODUCTION: Peripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical exercise increases the distance walked and improves quality of life. The aim of our study will be increased walking distance prolonging the time of onset of pain in patients with symptomatic PAD (IC). METHODS AND ANALYSIS: This study will be performed in Mataró Hospital's vascular surgery service and School of Health Sciences, TecnoCampus. This population comes from 15 primary healthcare centres ofNorth Barcelona, Spain (450 000 inhabitants).This study will be a four-group parallel, longitudinal, randomised controlled trial, blind to analysis.The main primary outcome of this study will be the improvement in pain-free walking distance. Others primary objectives are and improvement in functional status, quality of life and Ankle-Brachial Index (ABI). Secondary outcomes will be the analysis of cardiorespiratory fitness, evaluation of muscle fitness, determine the maintenance of primary objectives at 6 and 12 months.We will be included 124 patients (31 per group). The changes of the outcome (Barthel, SF-12, VascQOL-6, ABI) of the three intervention groups vs the control group at 3, 6 and 12 months will be compared, both continuously (linear regression) and categorically (logistic regression). A person who has not performed at least 75% of the training will be considered to have not completed the intervention. ETHICS AND DISSEMINATION: The study will be conducted according to the Declaration of Helsinki . It was approved by the Ethics Committee of the Research Institute Primary Health IDIAP Jordi Gol (20/035 P),Barcelona 6 October 2020. Informed consent will be obtained from all patients before the start of the study. We will disseminate results through academic papers and conference presentations. TRIAL REGISTRATION NUMBER: NCT04578990.

Relationship between Retinal Microvasculature, Cardiovascular Risk and Silent Brain Infarction in Hypertensive Patients.

OBJECTIVE: The aims of this study are to analyze the role of artery-vein ratio AVR assessment using VesselMap 2 software (Imedos Systems) and cardiovascular risk evaluation by means of REGICOR in the prediction of silent brain infarction (SBI) in middle-age hypertensive patients from the ISSYS study. MATERIAL AND METHODS: A cross-sectional study with 695 patients with hypertension aged 50 to 70 years who participated in the project Investigating Silent Strokes in HYpertensives: a Magnetic Resonance Imaging Study (ISSYS), was conducted in two Primary Care Centres of Barcelona. Participants agreed to a retinography and an MRI to detect silent brain infarction (SBI). The IMEDOS software was used for the semiautomatic caliber measurement of retinal arteries and veins, and the AVR was considered abnormal when <0.66. The REGICOR score was calculated for all patients. RESULTS: Multivariate logistic regression analysis was used to evaluate the impact of AVR and REGICOR scores on SBI. The OR (odds ratio) for a high REGICOR score and an abnormal AVR were 3.16 and 4.45, respectively. When analysing the interaction of both factors, the OR of an abnormal AVR and moderate REGICOR score was 3.27, whereas with a high REGICOR score it reached 13.07. CONCLUSIONS: The measurement of AVR in patients with hypertension and with a high REGICOR score can contribute to the detection of silent brain infarction.

Sex-Specific Protective Effects of APOE ε2 on Cognitive Performance.

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (ß = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and ß = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.

Long-Term Morbidity and Mortality after First and Recurrent Cardiovascular Events in the ARTPER Cohort.

BACKGROUND: Cardiovascular events are a major cause of mortality and morbidity worldwide. The risk of recurrence after a first cardiovascular event has been documented in the international literature, although not as extensively in a Mediterranean population-based cohort with low cardiovascular risk. There is also ample, albeit contradictory, research on the recurrence of stroke and myocardial infarctions (MI) after a first event and the factors associated with such recurrence, including the role of pathological Ankle-Brachial Index (ABI). METHODS: The Peripheral Arterial ARTPER study is aimed at deepening our knowledge of patient evolution after a first cardiovascular event in a Mediterranean population with low cardiovascular risk treated at a primary care centre. We study overall recurrence, cardiac and cerebral recurrence. We studied participants in the ARTPER prospective observational cohort, excluding patients without cardiovascular events or with unconfirmed events and patients who presented arterial calcification at baseline or who died. In total, we analyzed 520 people with at least one cardiovascular event, focusing on the presence and type of recurrence, the risk factors associated with recurrence and the behavior of the ankle-brachial index (ABI) as a predictor of risk. RESULTS: Between 2006 and 2017, 46% of patients with a first cardiovascular event experienced a recurrence of some type; most recurrences fell within the same category as the first event. The risk of recurrence after an MI was greater than after a stroke. In our study, recurrence increased with age, the presence of peripheral arterial disease (PAD), diabetes and the use of antiplatelets. Diabetes mellitus was associated with all types of recurrence. Additionally, patients with an ABI < 0.9 presented more recurrences than those with an ABI ≥ 0.9. CONCLUSIONS: In short, following a cardiac event, recurrence usually takes the form of another cardiac event. However, after having a stroke, the chance of having another stroke or having a cardiac event is similar. Lastly, ABI < 0.9 may be considered a predictor of recurrence risk.

[Reliability of retinography for the detection of hypertensive retinopathy in Primary Care]. / Fiabilidad de la retinografía para la detección de retinopatía hipertensiva en Atención Primaria.

OBJECTIVE: High blood pressure is one of the most prevalent diseases in general adult population. Its importance lies in the complications it causes in target organs such as kidney, heart, brain and eye. The aim of this work is to evaluate the agreement in the evaluation and interpretation of retinographies of hypertensive patients by family doctors and ophthalmologists. MATERIAL AND METHODS: This is a multicentric cross-sectional study in which 976 hypertensive patients from 50 to 70 years old were involved. They were participants of the «Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study¼ (ISSYS project) carried out in primary care centers of Barcelona and who agreed to undergo retinography. Six family physicians and 2 ophthalmologists evaluated the presence of retinal lesions through the Keith-Wagener-Barker criteria. RESULTS: The inter/intra-observer Kappa concordance of the evaluations was analyzed. The evaluation of the retinographies under the usual conditions of clinical practice obtained a high subjective component with slight and fair intra-observer concordance values in the Keith-Wagener-Barker criteria. Only the assessment of the microaneurysms showed a moderate concordance and the ratio artery/vein was the worst concordant. CONCLUSIONS: The evaluation of the retinographies in habitual conditions of clinical practice has a high subjective component that is reflected in slight and fair inter-intraobserver concordance values. The use of objective reading systems in the assessment of retinography in hypertensive patients would be useful.

Effects and Mechanisms of Cognitive, Aerobic Exercise, and Combined Training on Cognition, Health, and Brain Outcomes in Physically Inactive Older Adults: The Projecte Moviment Protocol.

INTRODUCTION: Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses. METHODS: One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention. RESULTS: Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample. DISCUSSION: Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03123900.

Low, borderline and normal ankle-brachial index as a predictor of incidents outcomes in the Mediterranean based-population ARTPER cohort after 9 years follow-up.

BACKGROUND: Guidelines recommended adopting the same cardiovascular risk modification strategies used for coronary disease in case of low Ankle-brachial index (ABI), but here exist few studies on long-term cardiovascular outcomes in patients with borderline ABI and even fewer on the general population. AIM: The aim of the present study was to analyze the relationship between long-term cardiovascular events and low, borderline and normal ABI after a 9-year follow up of a Mediterranean population with low cardiovascular risk. DESIGN AND SETTING: A population-based prospective cohort study was performed in the province of Barcelona, Spain. METHOD: A total of 3,786 subjects >49 years were recruited from 2006-2008. Baseline ABI was 1.08 ± 0.16. Subjects were followed from the time of enrollment to the end of follow-up in 2016 via phone calls every 6 months, systematic reviews of primary-care and hospital medical records and analysis of the SIDIAP (Information System for Primary Care Research) database to confirm the possible appearance of cardiovascular events. RESULTS: 3146 individuals participated in the study. 2,420 (77%) subjects had normal ABI, 524 (17%) had borderline ABI, and 202 (6.4%) had low ABI. In comparison with normal and borderline subjects, patients with lower ABI had more comorbidities, such as hypertension, hypercholesterolemia and diabetes. Cumulative MACE incidence at 9 years was 20% in patients with low ABI, 6% in borderline ABI and 5% in normal ABI. The annual MACE incidence after 9 years follow-up was significantly higher in people with low ABI (26.9/1000py) (p<0.001) than in borderline (6.6/1000py) and in normal ABI (5.6/1000py). Subjects with borderline ABI are at significantly higher risk for coronary disease (HR: 1.58; 95% CI: 1.02-2, 43; p = 0,040) compared to subjects with normal ABI, after adjustment. CONCLUSION: The results of the present study support that low ABI was independently associated with higher incidence of MACE, ICE, cardiovascular and no cardiovascular mortality; while borderline ABI had significantly moderate risk for coronary disease than normal ABI.

Correction: Contribution of the ankle-brachial index to improve the prediction of coronary risk: The ARTPER cohort.

[This corrects the article DOI: 10.1371/journal.pone.0191283.].

Safety of cilostazol in peripheral artery disease: a cohort from a primary healthcare electronic database.

BACKGROUND: Cilostazol has been associated with spontaneous reports of cardiovascular adverse events and serious bleeding. The objective of this study is to determine the relative risk of cardiovascular adverse events or haemorrhages in patients with peripheral artery disease treated with cilostazol in comparison to pentoxifylline users. METHODS: Population-based cohort study including all individuals older than 40 who initiated cilostazol or pentoxifylline during 2009-2011 in SIDIAP database. The two treatment groups were matched through propensity score (PS). RESULTS: Nine thousand one hundred twenty-nine patients met inclusion criteria and after PS matching, there were 2905 patients in each group. 76% of patients were men, with similar mean ages in both groups (68.8 for cilostazol and 69.4 for pentoxifylline). There were no differences in bleeding, cerebrovascular and cardiovascular events between both groups. CONCLUSIONS: Patients treated with cilostazol were different from those treated with pentoxifylline at baseline, so they were matched through PS. We did not find differences between treatment groups in the incidence of bleeding or cardiovascular and cerebrovascular events. Cilostazol should be used with precaution in elderly polymedicated patients.

Contribution of the ankle-brachial index to improve the prediction of coronary risk: The ARTPER cohort.

BACKGROUND: The different cardiovascular risk prediction scales currently available are not sufficiently sensitive. AIM: The aim of the present study was to analyze the contribution of the ankle-brachial index (ABI) added to the Framingham and REGICOR risk scales for the reclassification of cardiovascular risk after a 9-year follow up of a Mediterranean population with low cardiovascular risk. DESIGN AND SETTING: A population-based prospective cohort study was performed in the province of Barcelona, Spain. METHOD: A total of 3,786 subjects >49 years were recruited from 2006-2008. Baseline ABI was performed and cardiovascular risk was calculated with the Framingham and REGICOR scales. The participants were followed until November 2016 by telephone and review of the clinical history every 6 months to confirm the possible appearance of cardiovascular events. RESULTS: 2,716 individuals participated in the study. There were 126 incidental cases of first coronary events (5%) during follow up. The incidence of coronary events in patients with ABI <0.9 was 4-fold greater than that of subjects with a normal ABI (17.2/1,000 persons-year versus 4.8/1,000 persons-year). Improvement in the predictive capacity of REGICOR scale was observed on including ABI in the model, obtaining a net reclassification improvement of 7% (95% confidence interval 0%-13%) for REGICOR+ ABI. Framingham + ABI obtained a NRI of 4% (-2%-11%). CONCLUSION: The results of the present study support the addition of the ABI as a tool to help in the reclassification of cardiovascular risk and to confirm the greater incidence of coronary events in patients with ABI < 0.9.

Evolution and degree of control of cardiovascular risk factors after 5 years of follow-up and their relationship with the incidence of peripheral arterial disease: ARTPER cohort. / Evolución y grado de control de los factores de riesgo cardiovascular tras 5 años de seguimiento y su relación con la incidencia de arteriopatía periférica: cohorte poblacional ARTPER.

BACKGROUND AND OBJECTIVE: Although cardiovascular risk factors (CVRF) are well known, their degree of control is not optimal. The aim of this study is to assess the evolution and control of CVRFs after 5 years of monitoring a population-based cohort and their association with the incidence of peripheral arterial disease (PAD). MATERIAL AND METHOD: Prospective cohort study recruited between 2006-2008. Second phase between 2011-2012. An ankle brachial index was determined for all participants in both phases. Demographic variables, CVRF and previous cardiovascular events, blood pressure, total cholesterol and its fractions (HDL, LDL), triglycerides, glucose and glycosylated hemoglobin levels in diabetic patients and the cardiovascular risk score according to the REGICOR table were recorded. RESULTS: A total of 2,125 individuals were analyzed. We observed an increase in the prevalence of hypertension (HT) (15.4%), diabetes (DM) (8.2%) and hypercholesterolemia (20.4%), with no changes in obesity and smoking. The cardiovascular risk determined on the basis of the REGICOR table remained at around 5.5%. We observed an increased control of CVRF throughout the follow-up period, except in the case of DM and obesity. In the multivariate analysis, uncontrolled HT 2-folded the risk of onset of PAD (odds ratio [OR] 2.3; 95% confidence interval [95% CI] 1.3-4.1), whereas smoking 5-folded this risk (OR 5.0; 95% CI 2.5-10.2). CONCLUSIONS: Smoking and uncontrolled HT increase the risk of onset of PAD in this population. Despite the increase in drug treatments, the control of CVRFs continues to be suboptimal.

Incidence of peripheral arterial disease in the ARTPER population cohort after 5 years of follow-up.

BACKGROUND: To know the epidemiology (prevalence, incidence, progression and morbidity and mortality associated) of peripheral artery disease in general population and the factors associated with this progression is essential to know the evolution of atherosclerosis and develop preventive strategies. The aim of the study was to determine the incidence of PAD after 5 years of follow-up population-based cohort ARTPER, and the evolution of Ankle brachial Index (ABI) in this period. METHODS: Peripheral artery disease incidence analysis after 5 years of follow-up of 3786 subjects > 50 years old. Peripheral artery disease incident when the second cross section Ankle brachial Index was <0.9 in any of the lower limbs, with normal baseline (0.9 to 1.4). RESULTS: Between 2012 and 2013 2762 individuals (77% participation) were re-examined . Finally analyzed 2256 subjects (after excluding pathological Ankle brachial Index) followed for 4.9 years (range 3.8 to 5.8 years), totalling 11,106 person-years. Peripheral artery disease 95 new cases were detected, representing an incidence of 4.3% at 5 years and 8.6 per 1000 person-years (95% CI 6.9 to 10.5) being higher in men (10.2, 95% CI 7.4 to 13.5) than in women (7.5, 95% CI 5.5 to 9.9). Linear correlation between the baseline Ankle brachial Index and the second cross section was low (r = 0.23). CONCLUSIONS: The incidence of peripheral artery disease in ARTPER cohort was 8.6 cases per 1000 person-years, being higher in men, especially <65 years. The correlation between two measures Ankle brachial Index after 5 years of follow-up was low. One might consider whether Ankle brachial Index repeated measures could improve the correlation.

Evaluation of the relationship between effervescent paracetamol and blood pressure: clinical trial.

BACKGROUND: Paracetamol's solubility is achieved by adding to the excipient sodium salts, either as bicarbonate, carbonate or citrate. As the relationship between salt and hypertension is well known, due to the sodium content it has raised a hypothesis that may interfere with the control of that risk factor. Therefore, the objective of this study is to evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent, in hypertensive patients. METHODS/DESIGN: This is the protocol of a phase IV multicenter clinical trial, randomized, controlled, crossover, open, which will compare the effect of two different formulations of paracetamol (effervescent or non-effervescent) in the blood pressure of hypertensive patients, with a seven weeks follow up. 49 controlled hypertensive patients will be included (clinical BP lower than 150 and 95 mmHg, and lower than 135 mmHg and 85 mmHg in patients with diabetes or a history of cardiovascular event, and daytime ambulatory measurements lower than 140 and 90 mmHg) and mild to moderate pain (Visual Analog Scale between 1 and 4). The study was approved by the ethics committee of the Fundació Jordi Gol i Gurina and following standards of good clinical practice. The primary endpoint will be the variations in systolic BP in 24 h Ambulatory Blood Pressure Monitoring, considering significant differences 2 or more mmHg among those treated with non-effervescent and effervescent formulations. Intention-to-treat and per-protocol analysis will be held. DISCUSSION: Despite the broad recommendation not to use effervescent drugs in patients with hypertension, there are relatively little studies that show exactly this pressor effect due to sodium in salt that gives the effervescence of the product. This is the first clinical trial designed to study the effect of effervescence compared to the non-effervescent, in well-controlled hypertensive patients with mild to moderate pain, performed in routine clinical practice. TRIAL REGISTRATION: NCT 02514538.

Impairment of functional integration of the default mode network correlates with cognitive outcome at three months after stroke.

Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48-72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57-69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P = 0.014; threshold = 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t = 2.01); left parahippocampal gyrus and right superior frontal gyrus (t = 2.11); left parahippocampal gyrus and lSFG (t = 2.39); right parietal and lSFG (t = 2.29). Finally, mean path length obtained from graph-computation analysis showed positive correlations with semantic fluency test (r(s) = 0.454; P = 0.023), phonetic fluency test (r(s) = 0.523; P = 0.007) and the mini mental state examination (r(s) = 0.528; P = 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity.

Remote thalamic microstructural abnormalities related to cognitive function in ischemic stroke patients.

OBJECTIVE: Ischemic stroke can lead to a continuum of cognitive sequelae, ranging from mild vascular cognitive impairment to vascular dementia. These cognitive deficits can be influenced by the disruption of cortico-subcortical circuits. We sought to explore remote thalamic microstructural abnormalities and their association with cognitive function after ischemic stroke. METHOD: Seventeen patients with right hemispheric ischemic stroke and 17 controls matched for age, sex, and years of education were included. All participants underwent neurological, neuropsychological, and diffusion tensor image examination. Patients were assessed 3 months poststroke. Voxel-wise analysis was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) and mean diffusivity (MD) values in significant thalamic areas were calculated for each subject and correlated with cognitive performance. RESULTS: Stroke patients showed lower FA values and higher MD values in specific areas of both the left and right thalamus compared with controls. In patients, decreased FA values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.45, ß = 0.74) and the left thalamus (R(2) = 0.57, ß = 0.77) after adjusting for diabetes mellitus. Moreover, increased MD values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.27, ß = -0.54) after adjusting for diabetes mellitus. In controls, thalamic FA and MD values were not related to any cognitive function. CONCLUSION: Our findings support the hypothesis that ischemic stroke lesions are associated with remote thalamic diffusion abnormalities, and that these abnormalities can contribute to cognitive dysfunction 3 months after a cerebrovascular event.

[Concordance between 3 methods of measurement the ankle-brachial index to diagnose peripheral artery disease]. / Concordancia entre 3 métodos de medición del índice tobillo-brazo para el diagnóstico de arteriopatía periférica.

BACKGROUND AND OBJECTIVES: To determine the concordance of the ankle-brachial index (ABI) determined by automatic measurements (sphygmomanometer Omron and the triple cuff device) using doppler as the gold-standard, computing as well as sensitivity and specificity. PATIENTS AND METHODS: ARTPER population cohort subjects, classified as peripheral arterial disease (PAD) if ABI<0.9, calcified if ABI≥1.4 and healthy otherwise. To asses concordance we used kappa index using the 3 categories and the intraclass correlation coefficient (ICC) for ABI continuous values. RESULTS: Eighty-eight participants, 52% women, 57-87 years. It was possible to calculate the ABI using doppler for 100%, 97% using Omron and 95% using triple. ABI means (standard deviation) were: doppler 1.089 (0.236), Omron 1.082 (0.110), triple 1.146 (0.134), with poor agreement (ICC doppler/Omron=0.27, doppler/triple=0.13, and triple/Omron=0.39). Categorizing ABI as PAD-healthy-calcified 13.6% (doppler), 6.8% (Omron) and 3.4% (triple) were PAD and 9.1% (doppler), 1.1% (Omron) and 9.1% (triple) were calcified. Kappa indexes were weak (doppler/Omron=0.22, doppler/triple=0.01, triple/Omron=0.17). Both triple and Omron were highly specific (97%) but had very low sensitivity (8 and 33%, respectively) compared to doppler. CONCLUSIONS: Concordance of ABI automatic measurements as Omron and triple with doppler was poor, and they do not seem suitable for screening for PAD in primary care consultations.