Rigidez carotídea y riesgo de eventos vasculares y mortalidad: el estudio REGICOR / Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study

Introducción y objetivos: Los objetivos son analizar la relación dosis-respuesta de la rigidez de la arteria carótida y la mortalidad y evaluar su capacidad predictiva. Métodos: Estudio de cohorte poblacional que incluyó a 6.468 participantes, con una mediana de seguimiento de 6,5 años. Se evaluaron 6 índices de rigidez. Se identificaron los eventos coronarios y cerebrovasculares y la mortalidad. Resultados: La rigidez carotídea, el coeficiente de Peterson y la velocidad de la onda de pulso (VOP) se asociaron de manera lineal y directa con los eventos cerebrovasculares: aumento del 8% (IC95%, 1-16%) por unidad de rigidez, del 7% (IC95%, 2-13%) cada 10 unidades del coeficiente de Peterson y del 26% (IC95%, 8-48%) por unidad de la VOP. La tensión carotídea se asoció de modo no lineal con el riesgo de enfermedad coronaria: en valores <0,09 unidades, cada aumento de 0,01 unidades se asoció con una disminución de un 16% del riesgo (IC95%, –33 a +6%); por encima de 0,09 unidades, cada incremento de 0,01 unidades se asoció con un aumento de un 16% del riesgo (IC95%, 6-27%). La inclusión de estos índices no mejoró la capacidad predictiva de las funciones de riesgo. Conclusiones: La rigidez carotídea, el coeficiente de elasticidad de Peterson y la VOP tienen una relación lineal y directa con el riesgo de enfermedad cerebrovascular. La tensión (strain) carotídea tiene una relación en U con el riesgo de enfermedad coronaria. Estos índices no contribuyen a mejorar la capacidad predictiva de las funciones de riesgo. (AU)

Introduction and objectives: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. Methods: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. Results: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,−33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. Conclusions: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions. (AU)

Sex matters in the association between cardiovascular health and incident dementia: evidence from real world data.

BACKGROUND: Cardiovascular health has been associated with dementia onset, but little is known about the variation of such association by sex and age considering dementia subtypes. We assessed the role of sex and age in the association between cardiovascular risk and the onset of all-cause dementia, Alzheimer's disease, and vascular dementia in people aged 50-74 years. METHODS: This is a retrospective cohort study covering 922.973 Catalans who attended the primary care services of the Catalan Health Institute (Spain). Data were obtained from the System for the Development of Research in Primary Care (SIDIAP database). Exposure was the cardiovascular risk (CVR) at baseline categorized into four levels of Framingham-REGICOR score (FRS): low (FRS < 5%), low-intermediate (5% ≤ FRS < 7.5%), high-intermediate (7.5% ≤ FRS < 10%), high (FRS ≥ 10%), and one group with previous vascular disease. Cases of all-cause dementia and Alzheimer's disease were identified using validated algorithms, and cases of vascular dementia were identified by diagnostic codes. We fitted stratified Cox models using age parametrized as b-Spline. RESULTS: A total of 51,454 incident cases of all-cause dementia were recorded over a mean follow-up of 12.7 years. The hazard ratios in the low-intermediate and high FRS groups were 1.12 (95% confidence interval: 1.08-1.15) and 1.55 (1.50-1.60) for all-cause dementia; 1.07 (1.03-1.11) and 1.17 (1.11-1.24) for Alzheimer's disease; and 1.34 (1.21-1.50) and 1.90 (1.67-2.16) for vascular dementia. These associations were stronger in women and in midlife compared to later life in all dementia types. Women with a high Framingham-REGICOR score presented a similar risk of developing dementia - of any type - to women who had previous vascular disease, and at age 50-55, they showed three times higher risk of developing dementia risk compared to the lowest Framingham-REGICOR group. CONCLUSIONS: We found a dose‒response association between the Framingham-REGICOR score and the onset of all dementia types. Poor cardiovascular health in midlife increased the onset of all dementia types later in life, especially in women.

Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

Analysis of myocardial infarction incidence and case-fatality in the last three decades in the province of Girona.

INTRODUCTION AND OBJECTIVES: Myocardial infarction (MI) incidence and case fatality trends are highly informative but relatively untested at the population level. The objective of this work was to estimate MI incidence and case fatality in the Girona population aged 35-74 years, and to determine their 30-year trends (1990-2019). METHODS: The REGICOR (Girona Heart Registry) monitored MI incidence and case fatality rates from 1990 to 2008. For the period 2008 to 2019, we linked discharges from Girona hospitals (n=4 974 977) and mortality registry (n=70 405) during this period. Our linkage algorithm selected key MI diagnostic codes and removed duplicates. Estimates from the linkage algorithm and the REGICOR registry were compared using chi-square tests for overlapping years (2008-2009). We estimated the annual percent change (APC) of standardized MI incidence and 28-day case fatality, and analyzed their trends using joinpoint regression. RESULTS: MI incidence and case fatality estimates were similar in the linkage algorithm and the REGICOR registry. We observed significant decreasing trends in the incidence of MI. The trend was APC, -0.96% (95% confidence interval (95%CI), -1.4 to -0.53) in women from 1990 to 2019 and -4.2% (95%CI, -5.5 to -3.0) in men from 1994 to 2019. The largest decrease in case fatality was -3.8% (95%CI, -5.1 to -2.5) from 1995 to 2003 in women and -2.4% (95%CI, -2.9 to -1.9) from 1995 to 2004 in men, mainly due to prehospital case fatality declines: -1.8% (95%CI, -2.6 to -1.1) in men and -3.2% (95%CI, -4.6 to -1.8) in women. CONCLUSIONS: In Girona, MI incidence and case fatality decreased between 1990 and 2019. The incidence showed a slow but continuous decrease while case fatality only stabilized in the last decade, particularly in women.

La Red de Investigación en Actividades Preventivas y Promoción de la Salud (redIAPP): una red de referencia e impulsora de la investigación en atención primaria / The Research Network on Preventive Activities and Health Promotion (redIAPP): a reference network and promoter of primary care research

La Red de Investigación en Actividades Preventivas y Promoción de la Salud (redIAPP), una red de referencia e impulsora de la investigación en atención primaria fue creada en 2003 gracias al programa Redes Temáticas de Investigación Cooperativa en Salud (RETICS) del Instituto de Salud Carlos III (ISCIII). Su creación ha supuesto un cambio radical en la situación de la investigación en atención primaria. A lo largo de sus 19 años (2003-2021) han participado distintos grupos de investigación y comunidades autónomas, y se han desarrollado distintas líneas de investigación con numerosos proyectos y publicaciones. A pesar de las dificultades sufridas, ha creado una experiencia de investigación colaborativa entre distintas comunidades autónomas con gran vitalidad y con importantes resultados para la atención primaria. La redIAPP, por tanto, ha sido un gran referente para la investigación en atención primaria y para la profundización de su área de conocimiento. Se sugieren varias líneas de mejora para el futuro de la investigación en atención primaria.(AU)

The Research Network on Preventive Activities and Health Promotion (redIAPP), a reference network and promoter of primary care research was created in 2003 thanks to the program Thematic Networks for Cooperative Research in Health (RETICS) of the Instituto de Salud Carlos III (ISCIII). Its creation has meant a radical change in the situation of research in primary care. Throughout its 19 years (2003-2021), different research groups and autonomous communities have participated, and different lines of research have been developed with numerous projects and publications. Despite the difficulties suffered, it has created a collaborative research experience between different autonomous communities with great vitality and with important results for primary care. The redIAPP, therefore, has been a great reference for research in primary care and for the deepening of its area of knowledge. Several lines of improvement are suggested for the future of primary care research.(AU)

Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study.

INTRODUCTION AND OBJECTIVES: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. METHODS: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. RESULTS: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,-33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. CONCLUSIONS: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions.

Safety and immunogenicity of a recombinant protein RBD fusion heterodimer vaccine against SARS-CoV-2.

In response to COVID-19 pandemic, we have launched a vaccine development program against SARS-CoV-2. Here we report the safety, tolerability, and immunogenicity of a recombinant protein RBD fusion heterodimeric vaccine against SARS-CoV-2 (PHH-1V) evaluated in a phase 1-2a dose-escalation, randomized clinical trial conducted in Catalonia, Spain. 30 young healthy adults were enrolled and received two intramuscular doses, 21 days apart of PHH-1V vaccine formulations [10 µg (n = 5), 20 µg (n = 10), 40 µg (n = 10)] or control [BNT162b2 (n = 5)]. Each PHH-1V group had one safety sentinel and the remaining participants were randomly assigned. The primary endpoint was solicited events within 7 days and unsolicited events within 28 days after each vaccination. Secondary endpoints were humoral and cellular immunogenicity against the variants of concern (VOCs) alpha, beta, delta and gamma. All formulations were safe and well tolerated, with tenderness and pain at the site of injection being the most frequently reported solicited events. Throughout the study, all participants reported having at least one mild to moderate unsolicited event. Two unrelated severe adverse events (AE) were reported and fully resolved. No AE of special interest was reported. Fourteen days after the second vaccine dose, all participants had a >4-fold change in total binding antibodies from baseline. PHH-1V induced robust humoral responses with neutralizing activities against all VOCs assessed (geometric mean fold rise at 35 days p < 0.0001). The specific T-cell response assessed by ELISpot was moderate. This initial evaluation has contributed significantly to the further development of PHH-1V, which is now included in the European vaccine portfolio.ClinicalTrials.gov Identifier NCT05007509EudraCT No. 2021-001411-82.

Adipose tissue coregulates cognitive function.

Obesity is associated with cognitive decline. Recent observations in mice propose an adipose tissue (AT)-brain axis. We identified 188 genes from RNA sequencing of AT in three cohorts that were associated with performance in different cognitive domains. These genes were mostly involved in synaptic function, phosphatidylinositol metabolism, the complement cascade, anti-inflammatory signaling, and vitamin metabolism. These findings were translated into the plasma metabolome. The circulating blood expression levels of most of these genes were also associated with several cognitive domains in a cohort of 816 participants. Targeted misexpression of candidate gene ortholog in the Drosophila fat body significantly altered flies memory and learning. Among them, down-regulation of the neurotransmitter release cycle-associated gene SLC18A2 improved cognitive abilities in Drosophila and in mice. Up-regulation of RIMS1 in Drosophila fat body enhanced cognitive abilities. Current results show previously unidentified connections between AT transcriptome and brain function in humans, providing unprecedented diagnostic/therapeutic targets in AT.

Role of personal aptitudes as determinants of incident morbidity, lifestyles, quality of life, use of health services, and mortality (DESVELA cohort): quantitative study protocol for a prospective cohort study in a hybrid analysis.

Introduction: The healthcare and well-being of the population depend on multiple factors and should adapt to societal changes. The opposite is also occurring; society has evolved concerning the individuals' approach to their care, which includes participation in decision-making processes. In this scenario, health promotion and prevention become crucial to provide an integrated perspective in the organization and management of the health systems.Health status and well-being depend on many aspects, determinants of health, which in turn may be modulated by individual behavior. Certain models and frameworks try to study the determinants of health and individual human behaviors, separately. However, the interrelation between these two aspects has not been examined in our population.Our main objective is to analyze whether personal aptitudes related to behaviors are independently associated with the incidence of morbidity. A secondary objective will enquire whether these personal aptitudes are independently associated with lower all-cause mortality, enhanced adoption of healthy lifestyles, higher quality of life, and lower utilization of health services during follow-up. Methods: This protocol addresses the quantitative branch of a multicenter project (10 teams) for the creation of a cohort of at least 3,083 persons aged 35 to 74 years from 9 Autonomous Communities (AACC). The personal variables to evaluate are self-efficacy, activation, health literacy, resilience, locus of control, and personality traits. Socio-demographic covariates and social capital will be recorded. A physical examination, blood analysis, and cognitive evaluation will be carried out.Several sets of six Cox models (one for each independent variable) will analyze the incidence of morbidity (objective 1); all-cause mortality and the rest of the dependent variables (objective 2). The models will be adjusted for the indicated covariates, and random effects will estimate Potential heterogeneity between AACC. Discussion: The analysis of the association of certain behavioral patterns and determinants of health is essential and will contribute to improving health promotion and prevention strategies. The description of the individual elements and interrelated aspects that modulate the onset and persistence of diseases will allow the evaluation of their role as prognostic factors and contribute to the development of patient-tailored preventive measures and healthcare.Clinical Trial Registration: ClinicalTrials.gov, NCT04386135. Registered on April 30, 2020.

[The Research Network on Preventive Activities and Health Promotion (redIAPP): a reference network and promoter of primary care research]. / La Red de Investigación en Actividades Preventivas y Promoción de la Salud (redIAPP): una red de referencia e impulsora de la investigación en atención primaria.

The Research Network on Preventive Activities and Health Promotion (redIAPP), a reference network and promoter of primary care research was created in 2003 thanks to the program Thematic Networks for Cooperative Research in Health (RETICS) of the Instituto de Salud Carlos III (ISCIII). Its creation has meant a radical change in the situation of research in primary care. Throughout its 19 years (2003-2021), different research groups and autonomous communities have participated, and different lines of research have been developed with numerous projects and publications. Despite the difficulties suffered, it has created a collaborative research experience between different autonomous communities with great vitality and with important results for primary care. The redIAPP, therefore, has been a great reference for research in primary care and for the deepening of its area of knowledge. Several lines of improvement are suggested for the future of primary care research.

Role of personal aptitudes as determinants of incident morbidity, lifestyles, quality of life, use of the health services and mortality (DESVELA cohort): qualitative study protocol for a prospective cohort study in a hybrid analysis.

Introduction: Maintaining or acquiring healthier health-oriented behaviours and promoting physical and mental health amongst the Spanish population is a significant challenge for Primary Health Care. Although the role of personal aptitudes (characteristics of each individual) in influencing health behaviours is not yet clear, these factors, in conjunction with social determinants such as gender and social class, can create axes of social inequity that affect individuals' opportunities to engage in health-oriented behaviours. Additionally, lack of access to health-related resources and opportunities can further exacerbate the issue for individuals with healthy personal aptitudes. Therefore, it is crucial to investigate the relationship between personal aptitudes and health behaviours, as well as their impact on health equity. Objectives: This paper outlines the development, design and rationale of a descriptive qualitative study that explores in a novel way the views and experiences on the relationship between personal aptitudes (activation, health literacy and personality traits) and their perception of health, health-oriented behaviours, quality of life and current health status. Method and analysis: This qualitative research is carried out from a phenomenological perspective. Participants will be between 35 and 74 years of age, will be recruited in Primary Health Care Centres throughout Spain from a more extensive study called DESVELA Cohort. Theoretical sampling will be carried out. Data will be collected through video and audio recording of 16 focus groups in total, which are planned to be held in 8 different Autonomous Communities, and finally transcribed for a triangulated thematic analysis supported by the Atlas-ti program. Discussion: We consider it essential to understand the interaction between health-related behaviours as predictors of lifestyles in the population, so this study will delve into a subset of issues related to personality traits, activation and health literacy.Clinical trial registration: ClinicalTrials.gov, identifier NCT04386135.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

Five-Year Changes in Inflammatory, Metabolic, and Oxidative Biomarkers and 10-Year Cardiovascular Disease Incidence: The REGICOR Cohort Study.

Ischemic cardiovascular diseases (CVD) originate from an imbalance between atherosclerotic plaque formation, instability, and endothelial healing dynamics. Our aim was to examine the relationship between 5-year changes in inflammatory, metabolic, and oxidative biomarkers and 10-year CVD incidence in a population without previous CVD. This was a prospective cohort study of individuals aged 35-74 years (n = 419) randomly selected from 5263 REGICOR participants without CVD recruited in 2005. Biomarkers were measured at baseline and in 2010. Participants were followed up until 2020 for a composite CVD endpoint including coronary artery disease, stroke, and peripheral artery disease. We used Cox regression to analyze the effect of biomarker levels on the occurrence of the composite endpoint, adjusted for traditional CVD risk factors and baseline levels of each biomarker. Individuals with elevated IL-6 or insulin after 5 years had a higher independent risk of CVD at 10 years, compared to those with lower levels. Each rise of 1 pg/mL of IL-6 or 10 pg/mL of insulin increased the 10-year risk of a CVD event by 32% and 2%, respectively. Compared to a model with traditional CVD risk factors only, the inclusion of IL-6 and insulin improved continuous reclassification by 51%. Elevated serum levels of IL-6 and insulin were associated with a higher risk of CVD at 10 years, independently of traditional CVD risk factors.

Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome.

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial ß-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.

A multiple health behaviour change intervention to prevent depression: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of a 12-month MHBC intervention in the prevention of onset depression in primary health care (PHC). METHODS: Twenty-two PHC centres took part in the cluster-randomized controlled trial. Patients were randomized to receive either usual care or an MHBC intervention. The endpoints were onset of major depression and reduction of depressive symptoms in participants without baseline depression at a 12-month follow-up. RESULTS: 2531 patients agreed and were eligible to participate. At baseline, around 43% were smokers, 82% were non-adherent to the Mediterranean diet and 55% did not perform enough physical activity. The intervention group exhibited a greater positive change in two or more behaviours (OR 1.75 [95%CI: 1.17 to 2.62]; p = 0.006); any behaviour (OR 1.58 [95%CI: 1.13 to 2.20]; p = 0.007); and adherence to the Mediterranean diet (OR 1.94 [95%CI: 1.29 to 2.94]; p = 0.002), while this increase was not statistically significant for smoking and physical activity. The intervention was not effective in preventing major depression (OR 1.17; [95% CI 0.53 to 2.59)]; p = 0.690) or reducing depressive symptoms (Mean difference: 0.30; [95% CI -0.77 to 1.36]; p = 0.726) during follow-up. CONCLUSIONS: As compared to usual care, the MHBC intervention provided a non-significant reduction in the incidence of major depression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03136211.

Axes of social inequities in COVID-19 clinical trials: A systematic review.

Objective: The representativeness of participants is crucial to ensure external validity of clinical trials. We focused on the randomized clinical trials which assessed COVID-19 vaccines to assess the reporting of age, sex, gender identity, race, ethnicity, obesity, sexual orientation, and socioeconomic status in the results (description of the participants' characteristics, loss of follow-up, stratification of efficacy and safety results). Methods: We searched the following databases for randomized clinical trials published before 1st February 2022: PubMed, Scopus, Web of Science, and Excerpta Medica. We included peer-reviewed articles written in English or Spanish. Four researchers used the Rayyan platform to filter citations, first reading the title and abstract, and then accessing the full text. Articles were excluded if both reviewers agreed, or if a third reviewer decided to discard them. Results: Sixty three articles were included, which assessed 20 different vaccines, mainly in phase 2 or 3. When describing the participants' characteristics, all the studies reported sex or gender, 73.0% race, ethnicity, 68.9% age groups, and 22.2% obesity. Only one article described the age of participants lost to follow-up. Efficacy results were stratified by age in 61.9%, sex or gender in 26.9%, race and/or, ethnicity in 9.5%, and obesity in 4.8% of the articles. Safety results were stratified by age in 41.0%, and by sex or gender in 7.9% of the analysis. Reporting of gender identity, sexual orientation or socioeconomic status of participants was rare. Parity was reached in 49.2% of the studies, and sex-specific outcomes were mentioned in 22.9% of the analysis, most of the latter were related to females' health. Conclusions: Axes of social inequity other than age and sex were hardly reported in randomized clinical trials that assessed COVID-19 vaccines. This undermines their representativeness and external validity and sustains health inequities.

Design and deployment of ODISEA, an application for the myOcarDial infarction SafEtytrAnsfer of patients.

BACKGROUND: Rapid primary angioplasty is the most effective reperfusion strategy for acute ST-elevation myocardial infarction (STEMI) patients. Since not all hospitals have a catheterization laboratory to perform this intervention, adequate coordination of all medical professionals involved in the management of STEMI patients from the emergency room to the hospital catheterization laboratory is necessary. OBJECTIVE: Present the design and deployment of ODISEA (acronym of myOcarDial Infarction SafEtytrAnsfer), a web-based environment plus an application created to complement and support the transfer and management of STEMI patients from the first medical contact to the catheterization laboratory where the primary angioplasty will be carried out. METHOD: ODISEA is an application that has been designed to improve the coordination of all health personnel involved in the management of STEMI patients, i.e., primary care hospitals, Emergency Medical Services [EMS] and cardiology departments. The application provides: (i) functionalities to register relevant information of the patients' and the administered medications, (ii) a chat to coordinate all involved personnel; (iii) treatment recommendations for the first medical contact; and (iv) a GPS-SATELLITE monitoring system to know the exact position of the ambulance during patient transfer. These features improve the coordination in the catheterization laboratory, and optimize the equipment preparation time, and also the patient accommodation procedures after primary angioplasty. ODISEA registers all treated cases for a proper follow-up. The application has been tested from September 2021 to January 2022 in the context of a pilot study in Girona that involved 98 patients and 42 professionals (11 from hospital without Cath lab availability, 21 from EMS, and 10 from the main hospital). Professionals answered a questionnaire using a five-point Likert scale (satisfaction level from 1 to 5) to assess ODISEA regarding patient management, care quality, transfer coordination, transfer effectiveness, and usefulness. Collected data was analyzed using chi-square or Fisher's exact test. Statistical significance has been considered p < 0.05. To evaluate times of first angioplasty, relevant data from 98 patients was collected and compared with data of 129 STEMI patients not treated with ODISEA. RESULTS: For all the questions>70 % of answers are in the 3 to 5 range and from these, almost all the questions have 50 % of answers in the 4 and 5 range. Regarding groups of professionals only in the question related to coordination significant difference has been found for EMS professionals with respect to hospital without Cath lab availability and catheterization hospital professionals. Comparing ODISEA with no ODISEA patients it was observed an improvement in the times of first angioplasty as well as a reduction in the erroneous infarction codes activation. Patients treated with the ODISEA APP were further away from the PCI-capable center. A non-significant tendency was seen towards shorter primary angioplasty times (diagnostic electrocardiogram-guidewire passage) in the ODISEA compared to the NON ODISEA group (112 min vs 122 min; P =.3), a non-significant reduction of cases with times > 120 min (26.2 % vs 35.7 %, respectively; P =.1), and a tendency towards fewer cases eventually diagnosed as non-acute coronary syndrome (7.1 % vs 13.2 %; P =.1). CONCLUSION: ODISEA is a very well-accepted application that improves the management of STEMI patients. The application is an appropriate complement to current infarction protocol.

Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men.

Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.

Polyvascular Subclinical Atherosclerosis: Correlation Between Ankle Brachial Index and Carotid Atherosclerosis in a Population-Based Sample.

We assessed the correlation between the biomarkers of lower limb atherosclerosis (eg, ankle-brachial index [ABI]) and of carotid atherosclerosis (eg, common carotid intima-media thickness (IMT) and presence of atherosclerotic plaque) in a population-based cohort from Girona (Northwest Spain) recruited in 2010. Ankle-brachial index and carotid ultrasound were performed in all participants. Generalized additive multivariable models were used to adjust a regression model of common carotid IMT on ABI. Logistic regression multivariable models were adjusted to assess the probability of carotid plaque in individuals with peripheral artery disease. We included 3307 individuals (54.2% women), mean age 60 years (standard deviation 11). Two patterns of association were observed between subclinical biomarkers of atherosclerosis at the lower limb and carotid artery. Ankle-brachial index and common carotid IMT showed a linear trend in men [beta coefficient (95% confidence interval) =-.068 (-.123; -.012); P = .016]. Women with peripheral artery disease presented with high risk of atherosclerotic plaque at the carotid artery [Odds ratio (95% confidence interval) = 2.61, (1.46; 4.69); P = .001]. Men showed a significant linear association between ABI levels and common carotid IMT values. Women with peripheral artery disease presented with high risk of atherosclerotic plaque at the carotid artery.

Cardiovascular Risk Age Reflects Arterial Status: Middle-Aged People Showed Equivalent Arterial Stiffness to Older People in the Same Risk Category.

AIM: The concept of risk age may help overcome an excessive weight of age in cardiovascular risk functions. This study aimed to evaluate the equivalence of risk age with arterial stiffness by comparing people with increased risk age and individuals with the same chronological and risk age. In order to materialize this aim, we categorized individuals based on cardiovascular risk and compared groups with increased risk factors (other than age) and groups with normal levels. METHODS: This is a cross-sectional population-level study carried out in Girona province within the context of the REGICOR study (Girona Heart Registry). In this study, individuals aged 35-90 years who had a brachial-ankle pulse wave velocity measurement and with no previous cardiovascular disease or peripheral arterial disease were included. Cardiovascular risk was estimated with the FRESCO (in 35-79 year-olds), SCORE2 (in 35-69 year-olds), and SCORE2-OP (in 70-90 year-olds) functions and categorized to calculate and compare (in each category) the median chronological age in the group with increased risk factors and the reference. Arterial stiffness was assessed with the brachial-ankle pulse wave velocity (baPWV). The analyses were carried out separately by sex. RESULTS: In this study, 2499 individuals were included, with a mean age of 59.7 and 46.9% of men. Men presented worse health condition, including a higher mean cardiovascular disease risk score. Both men and women with increased levels of risk factors showed worse health condition than the respective men and women with optimal levels. In each risk category, the groups with higher risk age than chronological age (increased risk factors) were similar in baPWV values to the groups with the same chronological and risk ages (reference), who were consistently older. CONCLUSIONS: In categories with the same cardiovascular risk, the arterial stiffness of participants with a higher risk factor burden (increased risk age) matched that of older participants with the rest of the risk factors at optimal levels (same chronological and risk age). These results support the guidelines on the utilization of risk age to explain heightened cardiovascular risk, particularly among individuals in middle age.