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Background: Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD)., Methods: 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention., Results: The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05)., Conclusions: Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937., (© 2024. The Author(s).)

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population., Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC)., Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001)., Conclusions: Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m 2 , harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (βadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown., Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data., Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001)., Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Background: Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function., Methods: 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m 2 , were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention., Results: Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024)., Conclusions: Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease., Trial Registration: URL, http://www.cordioprev.es/index.php/en ., Clinicaltrials: gov number, NCT00924937., (© 2024. The Author(s).)

The incidence of type 2 diabetes mellitus (T2DM) is growing in Western countries. Nutritional interventions that promote high-quality dietary patterns could help reverse this trend. We aimed to evaluate whether changes in Nutrient-Rich Food Index 9.3 (NRF9.3) were related to the risk of developing T2DM in patients with coronary heart disease (CHD). The study was carried out in the context of two healthy dietary interventions (a Mediterranean and a low-fat diet). For this purpose, we evaluated all the patients in the CORDIOPREV study without T2DM at baseline. Data were obtained during the first 5 years of dietary intervention. The score was calculated using the Food Frequency Questionnaires at baseline and after 1 year of intervention. After 5 years of follow-up, 106 patients developed T2DM (incident-T2DM), while 316 subjects did not (non-T2DM). Total NRF9.3 score and changes during the first year of intervention were compared between incident-T2DM and non-T2DM. Incident-T2DM showed less improvement in NRF9.3 than non-T2DM ( p = 0.010). In the multi-adjusted Cox proportional hazard study, patients with greater improvement in NRF9.3 had over 50% less risk of developing T2DM compared with the lowest tertile (HR 2.10, 95%, CI = 1.12-3.56). In conclusion, improved diet quality in terms of nutrient density after the dietary intervention was associated with a lower risk of T2DM in patients with CHD.

Background: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years., Methods: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements., Findings: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group., Conclusion: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease., Trial Registration: Clinicaltrials.gov number NCT00924937., (© 2024. The Author(s).)

Background: Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women afflicted with CHD and delineate these against a non-CVD control group for each sex., Methods: Our research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our findings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software., Results: Our results showed a sex-specific variation (beta diversity) in the intestinal microbiota, while alpha-biodiversity remained consistent across both sexes. Linear discriminant analysis effect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identified seven bacterial taxa-g&#95;UBA1819 (Ruminococcaceae), g&#95;Bilophila, g&#95;Subdoligranulum, g&#95;Phascolarctobacterium, f&#95;Barnesiellaceae, g&#95;Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)-as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-afflicted and non-CVD individuals, when analyzed separately by sex., Conclusion: Our findings suggest a sex-specific dysbiosis in the intestinal microbiota linked to CHD, potentially contributing to the sex disparity observed in CVD incidence. Trial registration Clinical Trials.gov.Identifier NCT00924937., (© 2024. The Author(s).)

In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention ( n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period ( n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders ( p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (-0.19, 95% CI -0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (-0.35; 95% CI, -0.54 to -0.16; p < 0.001), and a low disposition index (-0.25; 95% CI, -0.47 to -0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline ( p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, -0.06-0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.

Aim: Advanced glycation end products (AGEs) play a role in kidney disease in type 2 diabetes mellitus (T2DM). However, there have been no prior controlled clinical trials examining the effects of specific diets on AGE metabolism and their impact on kidney function. Our aim was to assess whether modulating AGE metabolism resulting in reduced AGEs levels, after consumption of two healthy diets, could delay kidney function decline in patients with T2DM and coronary heart disease (CHD)., Methods: T2DM patients (540 out of 1002 patients from the CORDIOPREV study), with estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m 2 , were classified based on their baseline kidney function: normal eGFR (≥ 90 ml/min/1.73 m 2 ), mildly decreased eGFR (60- < 90 ml/min/1.73 m 2 ) and moderately decreased eGFR (<60 ml/min/1.73 m 2 ). Serum AGE levels, methylglyoxal (MG) and N-carboximethyllysine (CML), and gene expression related to AGE metabolism (AGER1, RAGE, and GloxI mRNA) were measured before and after 5-years of dietary intervention (a Mediterranean diet or a low-fat diet)., Results: Mediterranean diet produced a lower declined of eGFR compared to the low-fat diet only in patients with mildly decreased eGFR (P = 0.035). Moreover, Mediterranean diet was able to decrease MG levels and increase GloxI expression in normal and mildly decreased eGFR patients (all P < 0.05). One standard deviation increment of MG levels after dietary intervention resulted in a 6.8-fold (95 % CI 0.039;0.554) higher probability of eGFR decline., Conclusion: Our study showed that lowering circulating AGE levels, specifically MG, after following a Mediterranean diet, might be linked to the preservation of kidney function, evidenced by a decreased decline of eGFR in T2DM patients with CHD. Patients with mildly decreased eGFR could potentially benefit more from AGE reduction in maintaining kidney function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Atherosclerosis is the leading underlying cause of coronary heart disease (CHD). In patients with CHD, intima-media thickness of common carotid arteries (IMT-CC) is a reliable, validated, and non-invasive marker of the progression of atherosclerosis. Dietary intervention may affect IMT-CC evolution through different pathways. There is a lack of clinical trials evaluating the effect of total dietary antioxidant content of diets on IMT-CC, especially in patients with CHD., Objective: We evaluated the correlation between the diet's total antioxidant content and the changes in IMT-CC produced after 5 years of dietary intervention following two healthy diet models (Mediterranean diet and low-fat diet). We also evaluated whether the diet's total antioxidant content was related to the total redox capacity of the participants., Methods: From the total participants of the CORDIOPREV study (clinical trial register NCT00924937), 805 participants completed the IMT-CC measurement and the dietary antioxidant evaluation at baseline and after 5 years of dietary intervention. IMT-CC was carried out by ultrasound and the dietary antioxidant evaluation was performed by the Dietary Antioxidant Index (DAI). Additionally, direct redox balance was evaluated in a subset of population by the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) by colorimetric assay., Results: We observed an inverse correlation between evolution of DAI and IMT-CC after 5-years of dietary intervention. The mean of the DAI index augmented in the Mediterranean Diet group, whereas it decreased in the Low-fat group. DAI was correlated to the GSH/GSSG ratio, supporting DAI as an adequate estimator of diet's antioxidant content. When looking for individual components of the DAI that were associated to the changes in IMT-CC, an inverse correlation was found for carotenoids, vitamin E, vitamin C, and zinc and the IMT-CC., Conclusions: Our study indicates that, after five years of dietary intervention, changes in DAI inversely correlate with changes in IMT-CC in patients with CHD. Overall effect of Mediterranean diet resulted in an increase of DAI, conversely to low-fat. Specific elements included in the DAI index were inversely correlated with IMT-CC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims/hypothesis: There is a lack of e-health systems that integrate the complex variety of aspects relevant for diabetes self-management. We developed and field-tested an e-health system (POWER2DM) that integrates medical, psychological and behavioural aspects and connected wearables to support patients and healthcare professionals in shared decision making and diabetes self-management., Methods: Participants with type 1 or type 2 diabetes (aged >18 years) from hospital outpatient diabetes clinics in the Netherlands and Spain were randomised using randomisation software to POWER2DM or usual care for 37 weeks. This RCT assessed the change in HbA 1c between the POWER2DM and usual care groups at the end of the study (37 weeks) as a primary outcome measure. Participants and clinicians were not blinded to the intervention. Changes in quality of life (QoL) (WHO-5 Well-Being Index [WHO-5]), diabetes self-management (Diabetes Self-Management Questionnaire - Revised [DSMQ-R]), glycaemic profiles from continuous glucose monitoring devices, awareness of hypoglycaemia (Clarke hypoglycaemia unawareness instrument), incidence of hypoglycaemic episodes and technology acceptance were secondary outcome measures. Additionally, sub-analyses were performed for participants with type 1 and type 2 diabetes separately., Results: A total of 226 participants participated in the trial (108 with type 1 diabetes; 118 with type 2 diabetes). In the POWER2DM group (n=111), HbA 1c decreased from 60.6±14.7 mmol/mol (7.7±1.3%) to 56.7±12.1 mmol/mol (7.3±1.1%) (means ± SD, p<0.001), compared with no change in the usual care group (n=115) (baseline: 61.7±13.7 mmol/mol, 7.8±1.3%; end of study: 61.0±12.4 mmol/mol, 7.7±1.1%; p=0.19) (between-group difference 0.24%, p=0.008). In the sub-analyses in the POWER2DM group, HbA 1c in participants with type 2 diabetes decreased from 62.3±17.3 mmol/mol (7.9±1.6%) to 54.3±11.1 mmol/mol (7.1±1.0%) (p<0.001) compared with no change in HbA 1c in participants with type 1 diabetes (baseline: 58.8±11.2 mmol/mol [7.5±1.0%]; end of study: 59.2±12.7 mmol/mol [7.6±1.2%]; p=0.84). There was an increase in the time during which interstitial glucose levels were between 3.0 and 3.9 mmol/l in the POWER2DM group, but no increase in clinically relevant hypoglycaemia (interstitial glucose level below 3.0 mmol/l). QoL improved in participants with type 1 diabetes in the POWER2DM group compared with the usual care group (baseline: 15.7±3.8; end of study: 16.3±3.5; p=0.047 for between-group difference). Diabetes self-management improved in both participants with type 1 diabetes (from 7.3±1.2 to 7.7±1.2; p=0.002) and those with type 2 diabetes (from 6.5±1.3 to 6.7±1.3; p=0.003) within the POWER2DM group. The POWER2DM integrated e-health support was well accepted in daily life and no important adverse (or unexpected) effects or side effects were observed., Conclusions/interpretation: POWER2DM improves HbA 1c levels compared with usual care in those with type 2 diabetes, improves QoL in those with type 1 diabetes, improves diabetes self-management in those with type 1 and type 2 diabetes, and is well accepted in daily life., Trial Registration: ClinicalTrials.gov NCT03588104., Funding: This study was funded by the European Union's Horizon 2020 Research and Innovation Programme (grant agreement number 689444)., (© 2023. The Author(s).)

Background: Emerging evidence suggests that frailty may be a significant predictor of poor outcomes in older individuals hospitalized due to COVID-19. This study aims to determine the prognostic value of frailty on intrahospital patient survival., Methods: This observational, multicenter, nationwide study included patients aged 70 years and older who were hospitalized due to COVID-19 in Spain between March 1 and December 31, 2020. Patient data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine. Frailty was assessed using the Clinical Frailty Scale. The primary outcome was hospital survival. Cox proportional hazards models were used to assess predictors of survival., Results: A total of 1,878 participants (52% men and 48% women) were included, with 1,351 (71.9%) survivors and 527 (28.1%) non-survivors. The non-survivor group had higher mean age (83.5 vs. 81 years), comorbidities (6.3 vs. 5.3 points on the Charlson index), degree of dependency (26.8% vs. 12.4% severely dependent patients), and frailty (34.5% vs. 14.7% severely frail patients) compared to survivors. However, there were no differences in terms of sex. Our results demonstrate that a moderate-severe degree of frailty is the primary factor independently associated with shorter survival [HR 2.344 (1.437-3.823; p<0.001) for CFS 5-6 and 3.694 (2.155-6.330; p<0.001) for CFS 7-9]., Conclusion: Frailty is the main predictor of adverse outcomes in older patients with COVID-19. The utilization of tools such as the Clinical Frailty Scale is crucial for early detection in this population., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background and Aims: A critical telomere length (TL) is associated with cardiovascular mortality. Dietary habits have been demonstrated to affect cardiovascular risk. However, it remains unclear how exactly TL determines the response to specific dietary approaches in the reduction of arterial injury. We aimed to evaluate whether TL was associated with the progression of arterial injury (assessed by intima-media thickness of both common carotid arteries: IMT-CC), after long-term consumption of two healthy dietary models in patients with coronary heart disease (CHD)., Methods: From the 1002 CHD patients of the CORDIOPREV study, 903 completed IMT-CC and TL evaluation at baseline and were randomized to follow a Mediterranean diet or a low-fat diet for 5 years., Results: Patients at risk of short TL (TL < 20th percentile) presented an elevated IMT-CC, (0.79 ± 0.17 vs patients at non-risk 0.74 ± 0.17 p < 0.001). TL and IMT-CC showed an inverse association (β = -0.035, p = 0.002). Patients who consumed a Mediterranean diet, regardless of the risk of short TL, showed a significant decrease in IMT-CC, with a higher reduction in those patients with risk of short TL (-0.03 ± 0.11, p = 0.036). TL (β = 0.019, p = 0.024), age (β = -0.001, p = 0.031), energy intake (β = -0.000, p = 0.036), use of statins (β = -0.027, p = 0.028) and allocation into the Mediterranean diet (vs low-fat diet) (β = -0.024, p = 0.003) were significant contributors to changes in IMT-CC., Conclusions: Patients who had a reduced TL exhibited a greater decrease in IMT-CC after consuming a Mediterranean diet., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: We aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk., Methods: This study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60-40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out., Results: LC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%., Conclusion: Our study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development. Trials registration NCT00924937., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose of Review: Globalization and the increase in consumption of ultra-processed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners. This review aims to analyse the role of artificial sweeteners (nutritive and nonnutritive) and their impact on cardiometabolic and cardiovascular disease (CVD) risk., Recent Findings: The detrimental effects of a high-calorie, high-sugar diet have been well established. In light of this, health authorities recommend limiting sugar consumption. This has led the food industry to develop different artificial sweeteners with specific properties, such as flavour and stability (nutritive artificial sweeteners: NAS), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners: nNAS). Likewise, recent evidence explores the influence of artificial sweeteners (NAS and nNAS) on CVD risk through risk factors such as obesity and type 2 diabetes mellitus, among others., Summary: This review aims to provide an updated overview of the impact of NAS and nNAS on cardiovascular health and provide recommendations regarding their consumption., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Diabetes remission is a phenomenon described in the context of drastic weight loss due to bariatric surgery or low-calorie diets. Evidence suggests that increasing the intake of plant protein could reduce the risk of type 2 diabetes. We sought for association between changes in plant protein intake in the context of 2 healthy diets without weight loss nor glucose-lowering medication, and diabetes remission in coronary heart disease patients from the CORDIOPREV study., Methods: Newly diagnosed type 2 diabetes participants without glucose-lowering treatment were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was assessed with a median follow-up of 60 months according to the ADA recommendation. Information on patient's dietary intake was collected using food-frequency questionnaires. At first year of intervention, 177 patients were classified according to changes in plant protein consumption into those who increased or decreased its intake, in order to perform an observational analysis on the association between protein intake and diabetes remission., Results: Cox regression showed that patients increasing plant protein intake were more likely to remit from diabetes than those who decreased its intake (HR = 1.71(1.05-2.77)). The remission occurred mainly at first and second year of follow-up with diminished number of patients achieving remission in the third year onwards. The increase in plant protein was associated with lower intake of animal protein, cholesterol, saturated fatty acids, and fat, and with higher intake of whole grains, fibre, carbohydrates, legumes, and tree nuts., Conclusion: These results support the need to increase protein intake of vegetal origin as dietary therapy to reverse type 2 diabetes in the context of healthy diets without weight loss., (© 2023. The Author(s).)

Background and Objectives: A Mediterranean lifestyle may prevent and mitigate cardiometabolic disorders. We explored whether adherence to a Mediterranean lifestyle was prospectively associated with the risk of metabolic syndrome (MetS) among coronary heart disease (CHD) patients., Methods: The Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention (CORDIOPREV) study was an interventional diet study to compare a Mediterranean diet with a low-fat diet, in 1002 CHD patients. The Mediterranean lifestyle (MEDLIFE) index was used to assess adherence to a MEDLIFE at baseline, and after 5 years, in 851 participants from the CORDIOPREV study. Subjects were classified as having high (>13 points), moderate (12-13 points), and low (<12 points) adherence to the MEDLIFE. Multivariable logistic regression models were used to determine the association between MEDLIFE adherence and the risk of MetS development or reversal., Results: During the 5-year follow-up, CORDIOPREV participants with high adherence to MEDLIFE had a lower risk of MetS development (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19-0.75, p < 0.01) and a higher likelihood of reversing preexisting MetS (OR 2.08 CI 95% 1.11-3.91, p = 0.02) compared with participants in the low MEDLIFE adherence group. Each additional one-point increment in the MEDLIFE index was associated with a 24% lower risk of MetS development (OR 0.76, 95% CI 0.64-0.90, p < 0.01) and a 21% higher likelihood of reversing preexisting MetS (OR 1.21 CI 95% 1.04-1.41, p = 0.01)., Conclusions: Our results showed that greater adherence to a MEDLIFE reduced the risk of subsequent MetS development and increased the likelihood of reversing preexisting MetS among patients with CHD at baseline., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease and is also associated with other harmful entities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. NAFLD is a significant public health concern worldwide, impacting individuals of all ages, and its prevalence is projected to increase in the near future due to its connection with obesity. Intrinsic (genetics) and external (lifestyle) factors may also modulate NAFLD, and, in turn, may partly explain the observed relationship between NAFLD and cardiovascular disease (CVD). Although many drugs are been tested to treat NAFLD, to date, no drug has indication to specifically treat this disorder. Thus, the current management of NAFLD relies on lifestyle modifications and specifically on weight loss, physical activity, and the intake of a healthy diet. In the present narrative review, we will discuss the effects of certain dietary patterns on NAFLD incidence and progression.

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.

This study assesses the association between sleep duration and plasma lipid profiles in people with diabetes mellitus (DM). Sleep duration data were obtained in 91 patients from the POWER2DM study (NCT03588104). The patients were divided in tertiles, based on their sleep duration, and blood samples were obtained at the beginning and after 9 months. Significant differences were found, specifically, patients in Tertile 3 (≥ 7.51 h) showed lower plasma levels of high-density lipoprotein cholesterol HDL-c ( p  < 0.05), apolipoprotein A1 (apo-A1; p  < 0.05) and low HDL-c/apo-A1 ratio ( p  < 0.05). This study shows that sleep duration is associated with plasma lipid profiles in people with DM., Competing Interests: Conflict of interestIsabel Perez-Corral, Francisco Gomez-Delgado, Merel M Ruissen, Jose D Torres-Peña, Antonio P Arenas-de Larriva, Jacob K Sont, Albert A de Graaf, Bas S Uitbeijerse, Eelco J P de Koning and Javier Delgado-Lista declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background and Aims: The extent of atherosclerotic coronary heart disease (CHD) is associated with its prognosis, thus discovering potential biomarkers related to worse outcomes could prove valuable. The present work aims to investigate whether lipoprotein subfractions are associated with angiographic CHD severity., Materials and Methods: Patients from the CORDIOPREV study exhibiting coronary lesions in angiography were classified into two groups (single-vessel coronary disease (SVD) or multivessel coronary disease (MVD)). High-throughput nuclear magnetic resonance (NMR) spectroscopy determined lipoprotein subfractions concentration and composition., Results: SVD patients showed a higher concentration of medium and small HDL particles compared with MVD patients. For medium HDL, total lipids, phospholipids, total cholesterol, cholesteryl esters and free cholesterol reflected HDL particle concentration, whereas, for small HDL, total lipids, phospholipids, and free cholesterol mirrored lipoprotein particle concentration. Among traditional cardiovascular risk factors, age, hypertension and T2D were independently associated with angiography severity. In multivariate logistic regression models, medium and small HDL particles remained inversely associated with angiography severity (OR 0.77 (95% CI: 0.64-0.91); OR 0.78 (95% CI: 0.67-0.91), respectively) after adjusting with covariates., Conclusion: In CHD patients mostly on statin treatment, angiography severity is inversely related to small and medium HDL subclasses concentration measured by NMR. These particles are also independent predictors of the presence of MVD, and its use increased the prediction of this entity over traditional risk factors., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure., Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55-75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models., Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (β coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown., Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure., Competing Interests: JSS served on the board of the International Nut and Dried Fruit Council and receives grant support through this institution. He also served in the Executive Committee of the Instituto Danone, Spain, and on the Scientific Committee of the Danone International Institute. He received research support from the Patrimonio Comunal Olivarero, Spain, and Borges S.A., Spain. He received consulting fees or travel expenses from Eroski Foundation, the Instituto Danone, Spain, Mundipharma and Abbot Laboratories. ER reports grants, personal fees, non-financial support, and others from California Walnut Commission and Alexion, personal fees, non-financial support, and others from Ferrer International and Danone, and personal fees from Amarin, other than the submitted study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoury, Gómez-Donoso, Martínez, Martínez-González, Corella, Fitó, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, León-Acuña, Tinahones, Santos-Lozano, Serra-Majem, Massó Guijarro, Tur, Martín Sánchez, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Daimiel, Ros, Bes-Rastrollo, Barragan, Castañer, Torres-Peña, Notario-Barandiaran, Muñoz-Bravo, Abete, Prohens, Cano-Ibáñez, Tojal Sierra, Fernández-García, Sayon-Orea, Pascual, Sorli, Zomeño, Peña-Orihuela, Signes-Pastor, Basterra-Gortari, Schröeder, Salas Salvadó and Babio.)

Background and Aims: rs964184 variant in the ZPR1 gene has been associated with blood lipids levels both in fasting and postprandial state and with the risk of myocardial infarction in high-risk cardiovascular patients. However, whether this association is modulated by diet has not been studied., Objective: To investigate whether the type of diet (low-fat or Mediterranean diets) interacts with genetic variability at this loci to modulate fasting and postprandial lipids in coronary patients., Materials and Methods: The genotype of the rs964184 polymorphism was determined in the Cordioprev Study population (NCT00924937). Fasting and Postprandial triglycerides were assessed before and after 3 years of dietary intervention with either a Mediterranean or a low-fat diet. Postprandial lipid assessment was done by a 4-h oral fat tolerance test (OFTT). Differences in triglycerides levels were identified using repeated-measures ANCOVA., Results: From 523 patients (85% males, mean age 59 years) that completed the OFTT at baseline and after 3 years of intervention and had complete genotype information, 125 of them were carriers of the risk allele G. At the start of the study, these patients showed a higher fasting and postprandial triglycerides (TG) plasma levels. After 3 years of dietary intervention, G-carriers following a Mediterranean Diet maintained higher fasting and postprandial triglycerides, while those on the low-fat diet reduced their postprandial triglycerides to similar values to the population without the G-allele., Conclusion: After 3 years of dietary intervention, the altered postprandial triglyceride response induced by genetic variability in the rs964184 polymorphism of the ZPR1 gene can be modulated by a low-fat diet, better than by a Mediterranean diet, in patients with coronary artery disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alcala-Diaz, Arenas-de Larriva, Torres-Peña, Rodriguez-Cantalejo, Rangel-Zuñiga, Yubero-Serrano, Gutierrez-Mariscal, Cardelo, Luque, Ordovas, Perez-Martinez, Delgado-Lista and Lopez-Miranda.)

Individuals with evening chronotypes are prone to suffer chronodisruption and display worse lifestyle habits than morning-types, exhibiting higher cardiovascular diseases (CVD). However, it is unknown whether CVD patients, who are evening chronotypes, have higher cardiometabolic risk than morning-types. This study explored whether individual chronotypes were associated with cardiometabolic risk in patients from the CORDIOPREV study (n = 857). We also investigated whether potential associations were moderated by long-term consumption of two healthy diets (Mediterranean and Low-fat diets). This population was classified into chronotypes using the Morningness-Eveningness Questionnaire. Seven-day daily rhythms in wrist temperature (T), rest-activity (A) and position (P) were recorded in a subset of patients (n = 168), and an integrative variable TAP was determined. Metabolic Syndrome (MetS) was determined at baseline, and metabolic and inflammation markers were measured at baseline and yearly during the 4 years of follow-up. Differences in several lifestyle factors were analyzed according to chronotype. At all times, evening-types had higher triglycerides, C-reactive protein and homocysteine and lower high density lipoprotein cholesterol than morning-types (P < 0.05). Evening-types had a higher prevalence of MetS (OR 1.58 IC 95% [1.10 - 2.28], P = 0.01). Moreover, they were more sedentary, displayed less and delayed physical activity and ate and slept later. In addition, evening-types had lower amplitude, greater fragmentation, lower robustness and less stable circadian pattern at TAP (P < 0.01), all related to a less healthy circadian pattern. In conclusion, evening-types with CVD had higher cardiometabolic risk and less robust circadian-related rhythms than morning-types, regardless of the nutritional intervention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The individual influence of a variety of comorbidities on COVID-19 patient outcomes has already been analyzed in previous works in an isolated way. We aim to determine if different associations of diseases influence the outcomes of inpatients with COVID-19., Methods: Retrospective cohort multicenter study based on clinical practice. Data were taken from the SEMI-COVID-19 Registry, which includes most consecutive patients with confirmed COVID-19 hospitalized and discharged in Spain. Two machine learning algorithms were applied in order to classify comorbidities and patients (Random Forest -RF algorithm, and Gaussian mixed model by clustering -GMM-). The primary endpoint was a composite of either, all-cause death or intensive care unit admission during the period of hospitalization. The sample was randomly divided into training and test sets to determine the most important comorbidities related to the primary endpoint, grow several clusters with these comorbidities based on discriminant analysis and GMM, and compare these clusters., Results: A total of 16,455 inpatients (57.4% women and 42.6% men) were analyzed. According to the RF algorithm, the most important comorbidities were heart failure/atrial fibrillation (HF/AF), vascular diseases, and neurodegenerative diseases. There were six clusters: three included patients who met the primary endpoint (clusters 4, 5, and 6) and three included patients who did not (clusters 1, 2, and 3). Patients with HF/AF, vascular diseases, and neurodegenerative diseases were distributed among clusters 3, 4 and 5. Patients in cluster 5 also had kidney, liver, and acid peptic diseases as well as a chronic obstructive pulmonary disease; it was the cluster with the worst prognosis., Conclusion: The interplay of several comorbidities may affect the outcome and complications of inpatients with COVID-19.

(1) Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5−58.9) to 57.1 (44.1−67.1) vs. 71.5 (59.5−81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10−0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17−1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26−2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21−1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often.

Background & Aims: Lifestyle and dietary habits influence kidney function, playing an important role in the prevention and development of chronic kidney disease (CKD). The effectiveness of the Mediterranean diet in preserving kidney function has been seen in primary prevention. However, no scientific evidence is currently available to determine which dietary pattern is more effective in the management of CKD in secondary cardiovascular disease prevention. Thus, our aim was to evaluate the efficacy of the long-term consumption of two healthy dietary patterns (a Mediterranean diet rich in extra-virgin olive oil (EVOO) compared to a low-fat diet rich in complex carbohydrates) in preserving kidney function in coronary heart disease (CHD) patients., Methods: CHD patients (n = 1002) from the CORDIOPREV study were randomized to follow a Mediterranean diet (35% fat, 22% MUFA, <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, >55% carbohydrates). Kidney function was assessed by the determination of serum creatinine-based estimated glomerular filtration rate (eGFR) at baseline and after 5-years of dietary intervention. Patients were classified according to their type 2 diabetes (T2DM) status, using baseline eGFR (normal eGFR: ≥ 90 mL/min/1.73 m 2 ; mildly-impaired eGFR: 60 to <90 mL/min/1.73 m 2 , severely-impaired eGFR: <60 mL/min/1.73 m 2 ) to evaluate its influence on the progression of kidney function. Multiple linear regression analysis were performed to determine the contribution of different clinical and anthropometric parameters to changes in eGFR., Results: Although eGFR declined after both dietary interventions compared to baseline (all p < 0.001), the Mediterranean diet produced a lower decline of eGFR compared to the low-fat diet in patients with T2DM (p = 0.040). This effect was also observed when the overall population was considered (p = 0.033). No significant differences were observed in eGFR between the two diets in non-T2DM patients. In addition, this differential effect of the Mediterranean diet was mainly observed in patients with mildly-impaired eGFR in which this diet slowed eGFR progression (p = 0.002)., Conclusions: The long-term consumption of a Mediterranean diet rich in EVOO, when compared to a low-fat diet, may preserve kidney function, as shown by a reduced decline in eGFR in CHD patients with T2DM. Patients with mildly-impaired eGFR may benefit more from the beneficial effect of the consumption of the Mediterranean diet in preserving kidney function. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular disease prevention., Clinical Trial Registration: URL, http://www.cordioprev.es/index.php/en. Clinicaltrials.gov number, NCT00924937., Competing Interests: Conflict of interest The authors declare that they have no current or potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19., Methods: This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140-180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality., Results: Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140-180 mg) and 41.1% (>180 mg/dL), p <.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p <.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality., Conclusions: Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.

In order to assess whether previous hepatic IR (Hepatic-IR fasting ) and beta-cell functionality could modulate type 2 diabetes remission and the need for starting glucose-lowering treatment, newly-diagnosed type 2 diabetes participants who had never received glucose-lowering treatment (190 out of 1002) from the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (a prospective, randomized and controlled clinical trial), were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was defined according to the American Diabetes Association recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after oral glucose tolerance test, and having maintained them for at least 2 consecutive years. Patients were classified according to the median of Hepatic-IR fasting and beta-cell functionality, measured as the disposition index (DI) at baseline. Cox proportional hazards regression determined the potential for Hepatic-IR fasting and DI indexes as predictors of diabetes remission and the probability of starting pharmacological treatment after a 5-year follow-up. Low-Hepatic-IR fasting or high-DI patients had a higher probability of diabetes remission than high-Hepatic-IR fasting or low-DI subjects (HR:1.79; 95% CI 1.06-3.05; and HR:2.66; 95% CI 1.60-4.43, respectively) after a dietary intervention with no pharmacological treatment and no weight loss. The combination of low-Hepatic-IR fasting and high-DI presented the highest probability of remission (HR:4.63; 95% CI 2.00-10.70). Among patients maintaining diabetes, those with high- Hepatic-IR fasting and low-DI showed the highest risk of starting glucose-lowering therapy (HR:3.24;95% CI 1.50-7.02). Newly-diagnosed type 2 diabetes patients with better beta-cell functionality and lower Hepatic-IR fasting had a higher probability of type 2 diabetes remission in a dietary intervention without pharmacological treatment or weight loss, whereas among patients not achieving remission, those with worse beta-cell functionality and higher Hepatic-IR fasting index had the highest risk of starting glucose-lowering treatment after 5 years of follow-up., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease. The range is extensive, including hepatocellular carcinoma, cirrhosis, fibrosis, fatty liver, and non-alcoholic steatohepatitis (NASH). NASH is a condition related to obesity, overweight, metabolic syndrome, diabetes, and dyslipidemia. It is a dynamic condition that can regress to isolated steatosis or progress to fibrosis and cirrhosis. Statins exert anti-inflammatory, proapoptotic, and antifibrotic effects. It has been proposed that these drugs could have a relevant role in NASH. In this review, we provide an overview of current evidence, from mechanisms of statins involved in the modulation of NASH to human trials about the use of statins to treat or attenuate NASH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Torres-Peña, Martín-Piedra and Fuentes-Jiménez.)

Background: Obesity phenotypes with different metabolic status have been described previously. We analyzed metabolic phenotypes in obese coronary patients during a 5-year follow-up, and examined the factors influencing this evolution., Methods: The CORDIOPREV study is a randomized, long-term secondary prevention study with two healthy diets: Mediterranean and low-fat. All obese patients were classified as either metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO). We evaluated the changes in the metabolic phenotypes and related variables after 5 years of dietary intervention., Results: Initially, 562 out of the 1002 CORDIOPREV patients were obese. After 5 years, 476 obese patients maintained their clinical and dietary visits; 71.8% of MHO patients changed to unhealthy phenotypes (MHO-Progressors), whereas the MHO patients who maintained healthy phenotypes (MHO-Non-Progressors) lost more in terms of their body mass index (BMI) and had a lower fatty liver index (FLI-score) ( p < 0.05). Most of the MUO (92%) patients maintained unhealthy phenotypes (MUO-Non-Responders), but 8% became metabolically healthy (MUO-Responders) after a significant decrease in their BMI and FLI-score, with improvement in all metabolic criteria. No differences were found among dietary groups., Conclusions: A greater loss of weight and liver fat is associated with a lower progression of the MHO phenotype to unhealthy phenotypes. Likewise, a marked improvement in these parameters is associated with regression from MUO to healthy phenotypes.

Background and Purpose: Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk., Methods: From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, <50% carbohydrates) or a low-fat diet (28% fat, 12% monounsaturated fatty acids, >55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height., Results: The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P<0.001), maintained at 7 years (−0.031±0.008 mm; P<0.001), compared to baseline. The low-fat diet did not modify IMT-CC. IMT-CC and carotid plaquemax height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention., Conclusions: Long-term consumption of a Mediterranean diet rich in extravirgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00924937.

Acute respiratory distress syndrome (ARDS), resulting from an exaggerated inflammatory response, is the main cause of death from the coronavirus disease 2019 (COVID-19). Apart from respiratory infection, COVID-19 patients can develop cardiovascular disorders such as myocardial injury and myocarditis, pericarditis, cardiac arrest and arrhythmias, cardiomyopathy, heart failure, coagulation abnormalities and thrombosis. Statins can beneficially affect inflammation, oxidative stress, coagulation, thrombosis, angiotensin converting enzyme receptor, lipid rafts, and endothelial function. In this narrative review, we provide a critical overview of the current evidence and future perspectives on the use of statins to modulate the severity, duration and complications of COVID-19 through their pleiotropic properties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Torres-Peña, Katsiki and Perez-Martinez.)

Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient's risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p < 0.001) and reactive hyperaemia area (4233.3 ± 127.73 vs. 9695.9 ± 205.23 arbitrary perfusion units per time, 129.04% increase, p < 0.001) improved after the dietary intervention in the cohort, without finding differences due to the diet (p > 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups., (© 2021. The Author(s).)

Background: Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu., Methods: In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs)., Results: Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro-inflammatory response. In vitro, in VSMCs cultured in a pro-inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF-α, IL-1β, IL-6 and IL-8 and the activation of NF-κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg., Conclusion: Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality ( p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis ( p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continued treatment, and those taking ARB.

Coenzyme Q 10 (CoQ 10 ), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ 10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ 10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ 10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ 10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ 10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD.

Evidence suggests that enriching a diet with plant-based proteins could reduce the risk of developing type 2 diabetes mellitus. In the present work, we evaluated the association between the change in plant protein intake (adjusted by energy) and incidence of type 2 diabetes mellitus in patients with coronary heart disease from the CORDIOPREV (coronary diet intervention with olive oil and cardiovascular prevention) study. At baseline and during the follow-up, patients underwent medical examination and blood and oral glucose tolerance tests. Information on patient's dietary intake was gathered by registered dietitians using a validated food frequency questionnaire. A total of 106 out of 436 nondiabetic patients at baseline developed type 2 diabetes mellitus after a median follow-up of 60 months. Cox regression analyses showed that patients who belonged to the group that increased plant protein intake exhibited a lower risk of developing the disease (HR = 0.64, (0.43-0.96)). Changes in plant protein intake were positively correlated with changes in carbohydrates, fibre, and legumes intake and negatively correlated with changes in saturated fatty acids intake. Results of the present study support the need of improving diet with plant-based proteins to prevent the onset of type 2 diabetes mellitus.

Background: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization., Methods: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization., Results: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization., Conclusions: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.

Background: Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association., Methods: CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed., Results: The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment., Conclusions: Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 . Unique Identifier: NCT00924937.

Scope: The differences between the baseline gut microbiota of patients who developed type 2 diabetes (T2D) consuming a low-fat (LF) or a Mediterranean (Med) diet are explored and risk scores are developed to predict the individual risk of developing T2D associated with the consumption of LF or Med diet., Methods and Results: All the patients from the CORDIOPREV study without T2D at baseline (n = 462) whose fecal sample are available, are included. Gut microbiota is analyzed by 16S sequencing and the risk of T2D after a median follow-up of 60 months assessed by Cox analysis. Linear discriminant analysis effect size (LEfSe) analysis shows a different baseline gut microbiota in patients who developed T2D consuming LF and Med diets. A higher abundance of Paraprevotella, and lower Gammaproteobacteria and B. uniformis are associated with T2D risk when an LF diet is consumed. In contrast, higher abundances of Saccharibacteria, Betaproteobacteria, and Prevotella are associated with T2D risk when a Med diet is consumed., Conclusion: The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of T2D development, which may be used for selecting personalized dietary models to prevent T2D., (© 2020 Wiley-VCH GmbH.)

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay., Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100., Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays., Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.

Background: Spain has been one of the countries most affected by the COVID-19 pandemic., Objective: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease., Methods: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records., Results: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥80 years: 46.0%)., Conclusions: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality., (Copyright © 2020 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors. The mean age of the study population was 67.5 ± 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035). The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.

Background: Endothelial dysfunction is a crucial step in atherosclerosis development, and its severity is determinant for the risk of cardiovascular recurrence. Diet may be an effective strategy to protect the endothelium, although there is no consensus about the best dietary model. The CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) study is an ongoing prospective, randomized, single-blind, controlled trial in 1,002 coronary heart disease (CHD) patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat versus Mediterranean diet) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study: to evaluate the effect of these diets on endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery., Methods and Findings: From the total participants taking part in the CORDIOPREV study, 805 completed endothelial function study at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids [MUFAs], and <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFAs, and >55% carbohydrates), with endothelial function measurement repeated after 1 year. As secondary objectives and to explore different underlying mechanisms in the modulation of endothelial function, we quantified endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) and evaluated, in 24 preselected patients, in vitro cellular processes related to endothelial damage (reactive oxygen species, apoptosis, and senescence) and endothelial repair (cell proliferation and angiogenesis), as well as other modulators (micro-RNAs [miRNAs] and proteins). Patients who followed the Mediterranean diet had higher FMD (3.83%; 95% confidence interval [CI]: 2.91-4.23) compared with those in the low-fat diet (1.16%; 95% CI: 0.80 to 1.98) with a difference between diets of 2.63% (95% CI: 1.89-3.40, p = 0.011), even in those patients with severe endothelial dysfunction. We observed higher EPC levels (group difference: 1.64%; 95% CI: 0.79-2.13, p = 0.028) and lower EMPs (group difference: -755 EMPs/μl; 95% CI: -1,010 to -567, p = 0.015) after the Mediterranean diet compared with the low-fat diet in all patients. We also observed lower intracellular reactive oxygen species (ROS) production (group difference: 11.1; 95% CI: 2.5 to 19.6, p = 0.010), cellular apoptosis (group difference: -20.2; 95% CI: -26.7 to -5.11, p = 0.013) and senescence (18.0; 95% CI: 3.57 to 25.1, p = 0.031), and higher cellular proliferation (group difference: 11.3; 95% CI: 4.51 to 13.5, p = 0.011) and angiogenesis (total master segments length, group difference: 549; 95% CI: 110 to 670, p = 0.022) after the Mediterranean diet than the low-fat diet. Each dietary intervention was associated with distinct changes in the epigenetic and proteomic factors that modulate biological process associated with endothelial dysfunction. The evaluation of endothelial function is a substudy of the CORDIOPREV study. As in any substudy, these results should be treated with caution, such as the potential for false positives because of the exploratory nature of the analyses., Conclusions: Our results suggest that the Mediterranean diet better modulates endothelial function compared with a low-fat diet and is associated with a better balance of vascular homeostasis in CHD patients, even in those with severe endothelial dysfunction., Clinical Trial Registration: URL, http://www.cordioprev.es/index.php/en. clinicaltrials.gov number NCT00924937., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study., Methods: 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year., Results: From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet., Conclusions: A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.