Ruth Martí

Aims: Current guidelines suggest a unique 10 year cardiovascular disease (CVD) risk threshold for the oldest to consider lipid-lowering treatment for CVD prevention. We aimed to assess the benefit of initiating primary prevention with statins in non-diabetic adults aged 70–89 according to their SCORE2-OP, and to explore risk thresholds for different ages. Methods and results: We conducted an observational retrospective cohort study with the Catalan primary care database (SIDIAP) with an intention-to-treat approach. We assessed incident CVD (myocardial infarction and stroke), all-cause mortality, and adverse effects. Overall and age-stratified propensity-adjusted Cox proportional hazard models were fitted, using restricted cubic splines for the treatment interaction with SCORE2-OP. We analysed 167 360 individuals (mean age 77.70 years; 36.9% men). The mean baseline SCORE2-OP risk was 13.81%. Overall, treatment was not associated with a CVD reduction in lower risks, with a protective association becoming stable around a SCORE2-OP of 16% [hazard ratio (HR) = 0.90 (0.84–0.96)]. The different age groups reached similar protective associations (HR ≈ 0.85), but at different estimated risks. A mild significant increase of type 2 diabetes was observed in statin initiators [1.07 (1.02–1.12)]. We did not observe a protective association with all-cause mortality across the whole estimated risk spectrum. Conclusion: Age-specific risk thresholds of the SCORE2-OP estimated risk may be further developed and considered when weighing the benefits of initiating primary prevention of incident CVD with statins in non-diabetic adults aged 70 and older. Our results do not support treatment initiation of primary prevention to reduce all-cause mortality at any level of estimated CVD risk.

While associations between greenness and mental health have been studied, resilience, understood as the ability to adapt positively to stress and adversity, has received less attention. This study examined the relationship between the distance to the nearest park and resilience, considering potential gender differences. A cross-sectional study was conducted among 3,852 Spanish adults assigned to Primary Healthcare centers of nine autonomous communities. Resilience was assessed using the Connor-Davidson Resilience Scale. Unadjusted and adjusted differences in resilience and distance to the nearest park were assessed using Analysis of Variance, Analysis of Covariance, and multiple linear regression models in the total sample and stratified by sex. The covariates considered in this study were age, education, monthly income, marital status, perceived social support, and mental health. Sex was included as a covariate in analyses of the total sample. This study finally comprised 2,922 individuals, 52.0% women. The mean age of the participants was 53.6 years ± 10.9 SD. Participants living farther from parks (> 700 m) showed significantly lower resilience than those in the close (< 300 m; mean difference = 0.59, 95% CI: 0.06, 1.11, p = 0.028) and medium (300 m-700 m; mean difference = 0.82, 95% CI: 0.28, 1.35, p = 0.003) subgroups. Greater distance to the nearest park was inversely associated with resilience in the total sample (β = -0.040, 95% CI: -0.075, -0.003, p = 0.030). Stratified analyses revealed this association was significant among men (β = -0.060, 95% CI: -0.110, -0.009, p = 0.020), but not among women (β = -0.018, 95% CI: -0.068, 0.030, p = 0.463). Greater residential distance to the nearest park was associated with lower resilience in adults, especially in men. These findings highlight the potential importance of urban green space accessibility for promoting mental well-being, underscoring the need to consider gender in public health research and interventions.

This 1-year cohort study aimed to track long COVID prevalence, identify associated risk factors, and assess its association with hospitalization. The GINA-COVID cohort study included 2698 COVID-19 patients from Spain, who reported persistent symptoms spontaneously mentioned in an open questionnaire one year after infection. We recorded symptom onset, duration, and recovery rates at 12 months. Hospitalization data were collected from the Catalan Health System. We performed descriptive statistics and logistic regression models stratified by sex to identify factors associated with long COVID, using multiple imputation for missing values and model selection via stepwise regression based on the Akaike Information Criterion. Significant sex differences appeared, with females showing a two-fold higher risk of developing long COVID compared to males (OR=1.95; 95% CI, 1.68–2.29). Females reported higher prevalence and a greater number of persistent symptoms, with fatigue being the most common in both sexes (36% in females, 26% in males at 3 months). The recovery rate at 12 months was lower in females (23% vs. 34%, p<0.001). Hypertension emerged as the most significant protective factor for long COVID in females (OR=0.64; 95% CI, 0.48–0.84), whereas COVID-19 severity was the most influential risk factor in males (OR=2.34; 95% CI, 1.79–3.08). Despite these differences, the trajectory of persistent symptoms over time was similar between the sexes. Importantly, long COVID did not increase hospital admissions. Findings underscore the importance of sex-specific approaches in managing long COVID and suggest further investigation into hypertension’s protective role in females and disease severity’s impact in males.

We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined according to the World Health Organization definition. Global and sex-stratified genome-wide association analyses were conducted by logistic regression models adjusted for age, sex (in the global analysis), and the first 10 principal components. We assessed sex-variant interactions and performed gene-based analyses, gene mapping, and gene-set enrichment analyses. When comparing the 1392 long COVID cases with the non-cases, we identified 23 lead variants from suggestive signals: 13 from the global analysis, 5 from females, and 5 from males. Five variants showed a significant interaction with sex (two in females, three in males). We mapped 15 protein-coding genes related to diseases of the immune and nervous systems and tumoral processes. Notably, CD5 and VPS37C, linked to immune function, were significantly associated with long COVID in men. Our results suggest that persistent immune dysregulation may be involved in the development of precisely defined long COVID.

Background/Objectives: Although differences seem to exist by age in primary cardiovascular prevention with acetylsalicylic acid (ASA), direct comparisons are lacking, as are studies with real-world data. We sought to examine the effectiveness of ASA in reducing cardiovascular diseases and overall mortality in patients at high risk by age subgroups. Methods: We designed a retrospective cohort study using the database of the Catalan primary care system (SIDIAP), Spain, for the period 2006–2020. Included participants were high-cardiovascular-risk individuals without previous vascular disease. We considered people aged 40 to 59 and ≥60 years of age. We assessed the incidences of atherosclerotic cardiovascular disease (ASCVD), all-cause mortality, and ASA adverse effects using Cox proportional hazards modelling, adjusted by the propensity score of ASA treatment. Results: During the study period, 7576 and 30,282 people were aged 40 to 59 and ≥60 years, respectively. The median follow-up was 11.21 (10.71–11.54) years (40 to 59 year-olds) and 11.09 (10.55–11.54) years (≥60 year-olds). The hazard ratio of ASA use for ASCVD in the group aged 40–59 years was 0.64 (0.41–0.99). The number needed to treat in this group was 40 persons and the number that needed to harm for gastrointestinal bleeding (the only adverse effect with significant hazard ratio) was 75 individuals. Conclusions: This direct comparison of real-world age groups at high cardiovascular risk showed no benefit but increased risk in the older population (≥60 years). In the younger subgroup, our observations would support primary prevention with ASA with a consideration of the individual optimal risk–benefit.

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

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

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p<0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p<0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p<0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p<0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol <40 mg/dL in men or <50 mg/dL in women (OR = 1.70); (p<0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

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