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Background: The management in primary care (PC) of the patients with Heart Failure (HF) is different from the management hospital, in a special way compared to cardiology departments. Objective: To define the characteristics in both phenotypes of HF in prevalent and incident cases of HF in patients recruited in a large PC sample. Methods: We proposed a and longitudinal analyses, in patients of the IBERICAN cohort, that recruited 8,066 patients in the Spanish primary care system, with 15,488 patients-years of follow-up. Of them, 252 patients (3.1%) had diagnoses of HF. HF was classified according to the 2014 guidelines in two groups: HF with a reduced eject fraction or HFrEF (LVEF < 50%) and HF with preserved eject fraction or HFpEF (LVEF ≥ 50%). Recommended treatment was defined as the patient receiving drug treatment with Renin-Angiotensin-System (RAS) blockers with beta-blockers and, optionally, spironolactone. The incidence of new cases of HF was calculated in the 7,814 patients without HF in the inclusion visit. Finally, we analysed which variables associated the onset new cases and get the hazard ratio (HR) with the confidence interval at 95% ([95%CI]). Clinical trials register: NCT02261441 (02/05/2017). Results: The HFpEF was the most frequent phenotype in prevalent cases (61.1%) and incident cases (73.9%). Patients with HFrEF had a higher prevalence of coronary heart disease (p = 0.008) and PAD (p = 0.028), and no statistically significant differences was observed in the therapeutic groups used between both groups. The incidence of HF was 12.8 cases/1000 inhabitants/year, 35.6% of them was diagnosed in PC. The renin-angiotensin system blockers were more used in PC (60%) and beta-blockers (100%) and spironolactone (60%) in hospital. The female sex showed a protective effect for incident cases (0.51 [0.28–0.92]); and AF (HR [95%CI]: 2.90 [1.51–5.54]), coronary heart disease (HR [95%CI]: 2.18 [1.19-4.00]) and hypertension (HR [95%CI]: 1.91 [1.00-3.64]) increased the risk of developing HF. Conclusions: HF phenotype more frequent and incident in PC was the HFpEF, but only one third of them are diagnosed in PC level. The female sex showed a protective effect and atrial fibrillation, ischaemic heart disease and hypertension increased the risk of develop HF. [ABSTRACT FROM AUTHOR]

Background This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin–angiotensin–aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder. Methods Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts. Results The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92–3.41; P  < .0001). Conclusions In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment. [ABSTRACT FROM AUTHOR]

Worsening heart failure (HF) is associated with a high risk of death and rehospitalization. Despite that, real world evidence about the impact of worsening HF on clinical practice is scarce. A narrative review about registries addressing recent worsening HF events in Spain, with special emphasis on patients recently hospitalized for HF was performed. Worsening HF can be defined as situations where the patient's HF deteriorates to the extent that it necessitates initiation or intensification of diuretic treatment (mainly intravenous). The events can occur at the outpatient level, generally in the day hospital, in the emergency department or even hospitalization. Early identification of worsening HF events is essential to establish appropriate treatment as soon as possible. In this context, robust clinical benefits have been reported for renin-angiotensin system inhibitors, sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and vericiguat. In Spain, several registries of patients with HF have been developed, some of them including patients recently hospitalized for HF, but not with recent worsening HF events. Therefore, registries addressing recent worsening events would be desirable. Using a practical approach, this review analyzes the importance of worsening HF events, with special emphasis on Spanish data. [ABSTRACT FROM AUTHOR]

High blood pressure (HBP) is the leading risk factor for cardiovascular disease (CVD) and all-cause mortality worldwide. The progression of the disease leads to structural and/or functional alterations in various organs and increases cardiovascular risk. Currently, there are significant deficiencies in its diagnosis, treatment, and control. Vitamin D is characterized by its functional versatility and its involvement in countless physiological processes. This has led to the association of vitamin D with many chronic diseases, including HBP and CVD, due to its involvement in the regulation of the renin–angiotensin–aldosterone system. The aim of this study was to evaluate the effect of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolic pathway on the risk of developing HBP. An observational case-control study was performed, including 250 patients diagnosed with HBP and 500 controls from the south of Spain (Caucasians). Genetic polymorphisms in CYP27B1 (rs4646536, rs3782130, rs703842, and rs10877012), CYP2R1 rs10741657, GC rs7041, CYP24A1 (rs6068816, and rs4809957), and VDR (BsmI, Cdx2, FokI, ApaI, and TaqI) were analyzed by real-time PCR using TaqMan probes. Logistic regression analysis, adjusted for body mass index (BMI), dyslipidemia, and diabetes, showed that in the genotypic model, carriers of the GC rs7041 TT genotype were associated with a lower risk of developing HBP than the GG genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI): 0.41–0.77, p = 0.005, TT vs. GG). In the dominant model, this association was maintained; carriers of the T allele showed a lower risk of developing HBP than carriers of the GG genotype (OR = 0.69, 95% CI: 0.47–1.03; TT + TG vs. GG, p = 0.010). Finally, in the additive model, consistent with previous models, the T allele was associated with a lower risk of developing HBP than the G allele (OR = 0.65, 95% CI: 0.40–0.87, p = 0.003, T vs. G). Haplotype analysis revealed that GACATG haplotypes for SNPs rs1544410, rs7975232, rs731236, rs4646536, rs703842, and rs10877012 were associated with a marginally significant lower risk of developing HBP (OR = 0.35, 95% CI: 0.12–1.02, p = 0.054). Several studies suggest that GC 7041 is associated with a lower active isoform of the vitamin D binding protein. In conclusion, the rs7041 polymorphism located in the GC gene was significantly associated with a lower risk of developing HBP. This polymorphism could therefore act as a substantial predictive biomarker of the disease. [ABSTRACT FROM AUTHOR]

Aims: To describe healthcare resource utilization (HCRU) of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain.  METHODS: Adults with ≥ 1 HF diagnosis and ≥ 1 year of continuous enrolment before the corresponding index date (1/January/2016) were identified through the BIG-PAC database. Rate per 100 person-years of all-cause and HF-related HCRU during the year after the index date were estimated using bootstrapping with replacement.Results: Twenty-one thousand two hundred ninety-seven patients were included, of whom 48.5% had HFrEF, 38.6% HFpEF and 4.2% HFmrEF, with the rest being of unknown EF. Mean age was 78.8 ± 11.8 years, 53.0% were men and 83.0% were in NYHA functional class II/III. At index, 67.3% of patients were taking renin angiotensin system inhibitors, 61.2% beta blockers, 23.4% aldosterone antagonists and 5.2% SGLT2 inhibitors. Rates of HF-related outpatient visits and hospitalization were 968.8 and 51.6 per 100 person-years, respectively. Overall, 31.23% of patients were hospitalized, mainly because of HF (87.88% of total hospitalizations); HF hospitalization length 21.06 ± 17.49 days (median 16; 25th, 75th percentile 9-27). HF hospitalizations were the main cost component: inpatient 73.64%, pharmacy 9.67%, outpatient 9.43%, and indirect cost 7.25%. Rates of all-cause and HF-related HCRU and healthcare cost were substantial across all HF subgroups, being higher among HFrEF compared to HFmrEF and HFpEF patients.Conclusions: HCRU and cost associated with HF are high in Spain, HF hospitalizations being the main determinant. Medication cost represented only a small proportion of total costs, suggesting that an optimization of HF therapy may reduce HF burden. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence, incidence, and describe the characteristics and management of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain. Methods: Adults with ≥1 inpatient or outpatient HF diagnosis between 1 January 2013 and 30 September 2019 were identified through the BIG-PAC database. Annual incidence and prevalence by EF phenotype were estimated. Characteristics by EF phenotype were described in the 2016 and 2019 HF prevalent cohorts and outcomes in the 2016 HF prevalent cohort. Results: Overall, HF incidence and prevalence were 0.32/100 person-years and 2.34%, respectively, but increased every year. In 2019, 49.3% had HFrEF, 38.1% had HFpEF, and 4.3% had HFmrEF (in 8.3%, EF was not available). Compared with HFrEF, patients with HFpEF were largely female, older, and had more atrial fibrillation but less atherosclerotic cardiovascular disease. Among patients with HFrEF, 76.3% were taking renin-angiotensin system inhibitors, 69.5% beta-blockers, 36.8% aldosterone antagonists, 12.5% sacubitril/valsartan and 6.7% SGLT2 inhibitors. Patients with HFpEF and HFmrEF took fewer HF drugs compared to HFrEF. Overall, the event rates of HF hospitalization were 231.6/1000 person-years, which is more common in HFrEF patients. No clinically relevant differences were found in patients with HFpEF, regardless EF (50- < 60% vs. ≥60%). Conclusions: >2% of patients have HF, of which around 50% have HFrEF and 40% have HFpEF. The prevalence of HF is increasing over time. Clinical characteristics by EF phenotype are consistent with previous studies. The risk of outcomes, particularly HF hospitalization, remains high, likely related to insufficient HF treatment. [ABSTRACT FROM AUTHOR]

Objectives To assess mortality and cardiovascular and renal outcomes among patients with chronic kidney disease (CKD) (primary objective), with a particular focus on heart failure (HF) risk following diagnosis of CKD (secondary objective) in Spain. Methods We conducted an observational study comprising cross-sectional and longitudinal retrospective analyses using secondary data from electronic health records. For the primary objective, adults with prevalent CKD [estimated glomerular filtration rate (eGFR) <60 or ≥60 mL/min/1.73 m2 with a urine albumin:creatinine ratio (UACR) ≥30 mg/g at the index date (1 January 2017)] were included. For the secondary objective, adults with incident CKD in 2017 were enrolled. Results In the prevalent population, 46 786 patients with CKD without HF [75.8 ± 14.4 years, eGFR 51.4 ± 10.1 mL/min/1.73 m2; 75.1% on renin–angiotensin system inhibitors (RASis)] and 8391 with CKD and HF (79.4 ± 10.9 years, eGFR 46.4 ± 9.8 mL/min/1.73 m2) were included. In the prevalent population, the risk of all-cause death {hazard ratio [HR] 1.107 [95% confidence interval (CI) 1.064–1.153]}, HF hospitalization [HR 1.439 (95% CI 1.387–1.493)] and UACR progression [HR 1.323 (95% CI 1.182–1.481)] was greater in those patients with CKD and HF versus CKD only. For the incident population, 1594 patients with CKD without HF and 727 with CKD and HF were included. Within 24 months from the CKD diagnosis (with/without HF at baseline), 6.5% of patients developed their first HF hospitalization. Although 60.7% were taking RASis, only 3.4% were at maximal doses and among diabetics, 1.3% were taking sodium-glucose cotransporter-2 inhibitors. Conclusions The presence of HF among CKD patients markedly increases the risk of outcomes. CKD patients have a high risk of HF, which could be partially related to insufficient treatment. [ABSTRACT FROM AUTHOR]

Background Hyperkalaemia (HK) is a common electrolyte disorder in patients with chronic kidney disease (CKD) and/or treated with renin–angiotensin–aldosterone system inhibitors (RAASis). The aim of this study is to determine the severity, current management and cost of chronic HK. Methods We performed a retrospective cohort study of patients with chronic HK and CKD, heart failure or diabetes mellitus between 2011 and 2018. The study follow-up was 36 months. Results A total of 1499 patients with chronic HK were analysed: 66.2% presented with mild HK, 23.4% with moderate HK and 10.4% with severe HK. The severity was associated with CKD stage. Most patients (70.4%) were on RAASi therapies, which were frequently discontinued (discontinuation rate was 39.8, 49.8 and 51.8% in mild, moderate and severe HK, respectively). This RAASi discontinuation was similar with or without resin prescription. Overall, ion-exchange resins were prescribed to 42.5% of patients with HK and prescriptions were related to the severity of HK, being 90% for severe HK. Adherence to resin treatment was very low (36.8% in the first year and 17.5% in the third year) and potassium remained elevated in most patients with severe HK. The annual healthcare cost per patient with HK was €5929, reaching €12 705 in severe HK. Costs related to HK represent 31.9% of the annual cost per HK patient and 58.8% of the specialized care cost. Conclusions HK was usually managed by RAASi discontinuation and ion-exchange resin treatment. Most patients with HK were non-adherent to resins and those with severe HK remained with high potassium levels, despite bearing elevated healthcare expenditures. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory-syndrome coronavirus-2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2. This interaction has been proposed as a potential risk factor in patients treated with RAAS inhibitors.Objectives: This study analyzed whether RAAS inhibitors modify the risk for COVID-19.Methods: The RASTAVI (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation) trial is an ongoing randomized clinical trial randomly allocating subjects to ramipril or control groups after successful transcatheter aortic valve replacement at 14 centers in Spain. A non-pre-specified interim analysis was performed to evaluate ramipril's impact on COVID-19 risk in this vulnerable population.Results: As of April 1, 2020, 102 patients (50 in the ramipril group and 52 in the control group) were included in the trial. Mean age was 82.3 ± 6.1 years, 56.9% of the participants were male. Median time of ramipril treatment was 6 months (interquartile range: 2.9 to 11.4 months). Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving ramipril; hazard ratio: 1.150; 95% confidence interval: 0.351 to 3.768). The risk of COVID-19 was increased in older patients (p = 0.019) and those with atrial fibrillation (p = 0.066), lower hematocrit (p = 0.084), and more comorbidities according to Society of Thoracic Surgeons score (p = 0.065). Admission and oxygen supply was required in 4.9% of patients (2 in the ramipril group and 3 in the control group), and 4 of them died (2 in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p = 0.039).Conclusions: In a high-risk population of older patients with cardiovascular disease, randomization to ramipril had no impact on the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS inhibitor treatment during the COVID-19 crisis. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation [RASTAVI]; NCT03201185). [ABSTRACT FROM AUTHOR]

Frailty is a geriatric syndrome that identifies individuals at higher risk of disability, institutionalization, and death. We previously reported that frailty is related to oxidative stress and cognitive impairment-related biomarkers. The aim of this study was to determine whether frailty is associated with genetic variants. Longitudinal population-based cohort of 2488 community-dwelling people from Toledo, Spain, aged 65 years or older. We obtained blood samples from 78 individuals with frailty and 74 nonfrail individuals who were nonfrail (according to Fried criteria) from the Toledo Study of Healthy Ageing and extracted DNA using the Chemagic DNA blood kit. Sample genotyping was carried out by means of Axiom Exome 319 Genotyping Array (Thermo Fisher Scientific), which contains 295,988 markers [single-nucleotide polymorphisms (SNPs) and rare variants], and transferred to the GeneTitan Instrument (Affymetrix). We found 15 SNPs (P <.001), 18 genes (P <.005), and 4 pathways (P <.05) related to cytokine-cytokine receptor interaction, natural killer cell-mediated cytotoxicity, regulation of autophagy, and renin-angiotensin system as the most strongly associated with frailty. The specific genetic features related to energy metabolism, biological processes regulation, cognition, and inflammation highlighted by this preliminary analysis offer useful insights for finding biologically meaningful biomarkers of frailty that allow early diagnosis and treatment. Further research is needed to confirm our novel findings in a larger population. Indeed, the EU-funded FRAILOMICS research effort will address this question. [ABSTRACT FROM AUTHOR]

Drug treatment for secondary prevention of cardiovascular disease is recommended by guidelines, but it is not always followed in real life. This study wanted to assess the size of this gap and its impact on mortality in subjects after a cardiovascular event (MACE). Patients with any of MACE in the period from January 1st 2011 to December 31st 2013, and more than one year of follow-up were selected from population of the Valencian Community. Drugs for secondary prevention were antiplatelets, renin-angiotensin system blockers and statins. Assessment of treatment was performed one year after the initial event. Mortality risk was assessed using Cox by the number of drug classes (G0 no medication, G1 one, G2 two and G3 three drugs) adjusted by confounders. A total of 92,436 patients (62% men, mean age 72 years) of whom 60.5% presented with stroke, 30.6% with myocardial infarction and 8.9% with revascularization were included. Among them, 4.1% were G0, 20.2% G1, 32.9% G2 and 42.7% G3. A progressive decrease in mortality was observed in G1 (HR 0.83, CI 95% 0.73–0.95), G2 (HR 0.70, CI 95% 0.60–0.82) and G3 (HR 0.61, CI95% 0.51–0.74) vs. G0. In diabetic subgroup, significant reduction of risk was observed in the G2 (0.79, CI 95% 0.63–0.98) and G3 (0.72, CI9 5% 0.56–0.95), but not in G1 (0.97, CI 95% 0.80–1.17). A gap between guidelines and reality in the use of cardiovascular protecting drugs one year after the initial event still exists and it is largely related with all-cause late mortality. • Real world data will monitor compliance for secondary prevention of cardiovascular disease. • Less than half of the examined subjects were on an adequately three-drug prevention schedule. • The survival hazard ratios were progressively better as more drug classes were used for prevention. • Efforts should be done for improving compliance in secondary prevention. [ABSTRACT FROM AUTHOR]

The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location. [ABSTRACT FROM AUTHOR]

• The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression. • Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19. • Calcifediol seems to be able to reduce severity of the disease. The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. Parallel pilot randomized open label, double-masked clinical trial. University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. Results: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. Conclusions: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease. [ABSTRACT FROM AUTHOR]

Background: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19., Methods: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437., Findings: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62-2·41) and risk factors (1·46, 1·23-1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77-1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64-1·00) or angiotensin-receptor blockers (1·10, 0·88-1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34-0·80). The adjusted ORs were similar across severity degrees of COVID-19., Interpretation: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19., Funding: Instituto de Salud Carlos III., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Aims: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)-infected patients with decompensated hepatitis C virus (HCV)-related liver disease., Methods: Forty HIV/HCV co-infected patients and 40 HCV mono-infected patients, 20 of them with compensated cirrhosis and 20 with a previous decompensation, and 20 healthy controls, were studied. Intestinal permeability was determined by serum levels of lipopolysaccharide-binding protein (LBP). Monocyte expression of toll-like receptor 4 (TLR-4), serum levels of interleukin (IL)-6 and soluble receptors of tumour necrosis factor (sTNFRI) were analysed. Cardiac index, systemic vascular resistance (SVR), plasma renin activity (PRA) and aldosterone concentration were also determined in cirrhotic patients., Results: Serum levels of LBP, TLR-4, IL-6 and sTNFRI were significantly higher in HIV-HCV co-infected and HCV mono-infected patients with decompensated cirrhosis compared with those with compensated liver disease. Significantly lower values of SVR and higher values of cardiac index, PRA and aldosterone concentration were observed in patients with decompensated cirrhosis compared with those with compensated liver disease, particularly in those with elevated levels of IL-6. There were no significant differences between HIV/HCV co-infected and HCV mono-infected patients., Conclusions: Higher intestinal permeability and consequent macrophage activation is observed in patients with cirrhosis; this permeability is even higher in those with portal hypertension. Serum values of IL-6 are associated with the characteristic haemodynamic derangement observed in advanced phases of cirrhosis. HIV/HCV co-infected cirrhotic patients present inflammatory and systemic haemodynamic alterations similar to those observed in HCV mono-infected patients., (© 2011 John Wiley & Sons A/S.)