Potential role of new molecular plasma signatures on cardiovascular risk stratification in asymptomatic individuals

The evaluation of cardiovascular (CV) risk is based on equations derived from epidemiological data in individuals beyond the limits of middle age such as the Framingham and SCORE risk assessments. Lifetime Risk calculator (QRisk®), estimates CV risk throughout a subjects' lifetime, allowing those. A more aggressive and earlier intervention to be identified and offered protection from the consequences of CV and renal disease. The search for molecular profiles in young people that allow a correct stratification of CV risk would be of great interest to adopt preventive therapeutic measures in individuals at high CV risk. To improve the selection of subjects susceptible to intervention with aged between 30-50 years, we have employed a multiple proteomic strategy to search for new markers of early CV disease or reported CV events and to evaluate their relationship with Lifetime Risk. Blood samples from 71 patients were classified into 3 groups according to their CV risk (healthy, with CV risk factors and with a previously reported CV event subjects) and they were analyzed using a high through quantitative proteomics approach. This strategy allowed three different proteomic signatures to be defined, two of which were related to CV stratification and the third one involved markers of organ damage.This work was supported by grants from the Instituto de Salud Carlos III (PI070537, IF08/3667-1, PI11-02239, PI 14/01917, PI11/01401, PI11/02432, PI13/01873, PI13/01746, PI13/01581, PI14/01650, PI14/01841), PT13/0001/0013, PIE13/00051, PIE13/00045, CP09/00229, CP15/00129, IDC Salud (3371/002), the MutuaMadrileña Foundation, the SENEFRO Foundation and FONDOS FEDER (RD06/0014/1015, RD12/0042/0071). Sociedad Española de cardiología para la Investigación Básica 2017. Grant PRB3 (IPT17/0019 - ISCIII-SGEFI / ERDF. These results are in line with the Spanish initiative on the Human Proteome Project.S

Lipoprotein(A) Concentrations In Rheumatoid Arthritis On Biologic Therapy: Results From The Cardiovascular In Rheumatology [Carma] Study Project

Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (?: ?0.303, 95% confidence interval: ?0.558 to ?0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results, and preparation of the article have been done independently of Abbvie. Dr González-Gay's studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, and PI12/00060 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Disponibilidad y promoción de alcohol según la tipología de los locales y las condiciones socioeconómicas del área

Smoking and substance use during pregnancy are major preventable causes of mortality and morbidity, having a bidirectional and deleterious relationship with the mental health of the mother and child. As part of the WOMAP (Woman Mental Health and Addictions on Pregnancy) initiative, our study aimed to describe the prevalence of co-occurring mental illness and substance use problems, diagnoses and severity of those considered at risk and rates of treatment.A screening of 2,014 pregnant women was done using the AC-OK scale and they were asked about their smoking habits and services use for mental health/substance abuse. Of these, 170 women were considered at risk of co-occurring mental illness and substance use problems (≥ 2 positive responses to the AC-OK-Mental Health subscale, ≥ 1 positive response to the AC-OK-Substance Abuse subscale and/or smoking more than once a month and no use of specialized services) and were assessed with a more extensive battery of measures (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Posttraumatic stress disorder [PTSD] Checklist for DSM-5 [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] and Fagerström).In the last year, 614 women (30.5%) smoked tobacco (42.5% daily) and 9.8% were positive for both substance use and mental illness per the AC-OK. Only 11.1% of them received specific treatment in the previous three months while another 13.6% were scheduled to attend services in the following month. From the subsample assessed in depth, 62(36.5%) endorsed at least moderate depression, 35(20.6%) endorsed at least moderate anxiety, 32(18.8%) endorsed PTSD on the PCL, and 37 out of 88 alcohol users scored above the threshold in AUDIT (≥ 3).In conclusion, high prevalence and low treatment rates suggest that effective detection mechanisms should be integrated into usual care, allowing for early interventions. ------------------------------------------------------------------ El tabaquismo y el consumo de sustancias durante el embarazo son importantes causas prevenibles de morbimortalidad, teniendo una relación bidireccional y deletérea con la salud mental de la madre y el niño. Como parte de la iniciativa WOMAP (Woman Mental Health and Addictions on Pregnancy), se estudiaron 2014 embarazadas buscando describir la prevalencia de trastornos mentales y por uso de sustancias concurrentes, las tasas de tratamiento y los diagnósticos y la gravedad. Las participantes fueron evaluadas con la escala AC-OK y se les preguntó sobre sus hábitos tabáquicos y uso de servicios de salud mental/sustancias. De las participantes, 170 mujeres resultaron positivas para un trastorno mental y por uso de sustancias concurrentes (≥ 2 positivos a la subescala AC-OK-Salud Mental, ≥ 1 positivos a la subescala AC-OK-Sustancias y/o fumar más de una vez al mes y no estar en tratamiento) y fueron evaluadas en profundidad mediante una batería de escalas (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Post-traumatic stress disorder Checklist [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] y Fagerström). En el último año, 614 mujeres (30,5 %) fumaron tabaco (42,5 % diariamente) y el 9,8 % fueron positivas para problemas por uso de sustancias y salud mental según la AC-OK. Solo el 11,1 % había recibido tratamiento en los tres meses previos y solo un 13,6 % tenía una cita en el siguiente mes. De las 170 pacientes evaluadas secundariamente, 62(36,5 %) presentaron al menos depresión moderada, 35(20,6 %) al menos ansiedad moderada, 32(18,8 %) fueron positivas a la PCL-5, y 37 de las 88 que reconocieron uso de alcohol puntuaron por encima del umbral en AUDIT (≥ 3). En conclusión, la combinación de una prevalencia significativa junto con bajas tasas de tratamiento, remarcan la necesidad de mecanismos de detección efectivos en la atención habitual, permitiendo una intervención temprana.2020-2

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function: The 2-Year Longitudinal Changes in an Older Spanish Cohort

Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55-75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, β: −0.054; 95% CI: −0.110, − 0.002, P-trend = 0.047) and Part B (TMT-B, β: −0.079; 95% CI: −0.134, −0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years

How Did the COVID-19 Lockdown Pandemic Affect the Depression Symptomatology in Mediterranean Older Adults with Metabolic Syndrome?

Background and Aims. To control the COVID-19 spread, in March 2020, a forced home lockdown was established in Spain. In the present study, we aimed to assess the effect of mobility and social COVID-19-established restrictions on depressive symptomatology in older adults with metabolic syndrome. We hypothesize that severe restrictions might have resulted in detrimental changes in depressive symptomatology. Methods. 2,312 PREDIMED-Plus study participants (men = 53:9%; mean age = 64:9±4:8 years) who completed a COVID-19 lockdown questionnaire to assess the severity of restrictions/lockdown and the validated Spanish version of the Beck Depression Inventory-II (BDI-II) during the three established phases concerning the COVID-19 lockdown in Spain (prelockdown, lockdown, and postlockdown) were included in this longitudinal analysis. Participants were categorized according to high or low lockdown severity. Analyses of covariance were performed to assess changes in depressive symptomatology across lockdown phases. Results. No significant differences in participant depression symptomatology changes were observed between lockdown severity categories (low/high) at the studied phases. During the lockdown phase, participants showed a decrease in BDI-II score compared to the prelockdown phase (mean (95% CI), -0.48 (-0.24, -0.72), P < 0:001); a nonsignificantly larger decrease was observed in participants allocated in the low-lockdown category (low: -0.59 (-0.95, -0.23), high: -0.43 (-0.67, -0.19)). Similar decreases in depression symptomatology were found for the physical environment dimension. The post- and prelockdown phase BDI-II scores were roughly similar. Conclusions. The COVID-19 pandemic lockdown was associated with a decrease in depressive symptomatology that returned to prelockdown levels after the lockdown. The degree of lockdown was not associated with depressive symptomatology. The potential preventive role of the physical environment and social interactions on mental disorders during forced home lockdown should be further studie

Dietary diversity and Depression: Cross-sectional and longitudinal analyses in Spanish adult population with Metabolic Syndrome. Findings from PREDIMED-PLUS Trial.

Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between Dietary Diversity (DD) and depressive symptoms. Design: An energy-adjusted Dietary Diversity Score (DDS) was assessed using a validated food-frequency questionnaire and was categorized into quartiles (Q). The variety in each food group was classified into 4 categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II>=18. Linear and logistic regression models were used. Setting: Spanish older adults with Metabolic Syndrome. Participants: A total of 6625 adults aged (55-75 years) from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; Odds Ratio (OR) Q4 vs Q1= 0.76 (95% confidence interval (CI): 0.64, 0.90). This was driven by high diversity compared to low diversity (C3 vs. C1) of vegetables [OR (95%CI) = 0.75 (0.57, 0.93)], cereals [OR (95%CI) = 0.72 (0.56-0.94)] and proteins [OR (95%CI) = 0.27 (0.11, 0.62)]. In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 y- of follow-up, except for DD in vegetables C4 vs C1= [β (95%CI) = 0.70 (0.05, 1.35)]. Conclusions: According to our results, DD is associated with the presence of depressive symptoms but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up period) are needed to confirm these findings

Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms

Total and Subtypes of Dietary Fat Intake and Its Association with Components of the Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Risk

Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55-75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and ω-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3-1.6 times higher for total fat, MUFA, SFA and ω-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and ω-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia