Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients.

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.

Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial.

BACKGROUND: Cardiovascular (CV) polypills are a useful baseline treatment to prevent CV diseases by combining different drug classes in a single pill to simultaneously target more than one risk factor. The aim of the present trial was to determine whether the treatment with the CNIC-polypill was at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDL-c) and systolic BP (SBP) values in subjects at high or very high risk without a previous CV event. METHODS: The VULCANO was an international, multicentre open-label trial involving 492 participants recruited from hospital clinics or primary care centres. Patients were randomised to the CNIC-polypill -containing aspirin, atorvastatin, and ramipril- or usual care. The primary outcome was the comparison of the mean change in LDL-c and SBP values after 16 weeks of treatment between treatment groups. RESULTS: The upper confidence limit of the mean change in LDL-c between treatments was below the prespecified margin (10 mg/dL) and above zero, and non-inferiority and superiority of the CNIC-polypill (p = 0.0001) was reached. There were no significant differences in SBP between groups. However, the upper confidence limit crossed the prespecified non-inferiority margin of 3 mm Hg. Significant differences favoured the CNIC-polypill in reducing total cholesterol (p = 0.0004) and non-high-density lipoprotein cholesterol levels (p = 0.0017). There were no reports of major bleeding episodes. The frequency of non-serious gastrointestinal disorders was more frequent in the CNIC-polypill arm. CONCLUSION: The switch from conventional treatment to the CNIC-polypill approach was safe and appears a reasonable strategy to control risk factors and prevent CVD. Trial registration This trial was registered in the EU Clinical Trials Register (EudraCT) the 20th February 2017 (register number 2016-004015-13; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-004015-13 ).

Peripheral Atherosclerosis in Patients With Erectile Dysfunction: A Population-Based Study.

INTRODUCTION: The presence of erectile dysfunction (ED) could be a warning of vascular disease in different arterial territories. AIM: The aim of this study was to investigate the association between ED and the presence of atherosclerosis in 2 different vascular beds: carotid and lower limbs. METHODS: A total of 614 volunteers between 45 and 74 years of age (mean age 61.0 years) were randomly selected from the general population. ED was assessed using the International Index of Erectile Function (IIEF-5). Ankle-brachial index (ABI) measurement and carotid atherosclerosis were evaluated by echo-Doppler. MAIN OUTCOME MEASURES: Mean carotid intima-media thickness (IMT), prevalence of carotid plaques, mean ABI, and prevalence of ABI < 0.9 were the main outcome measures. RESULTS: ED was present in 373 subjects (59.7%). Mean carotid IMT was significantly higher in men with ED (0.762 ± 0.151 mm vs 0.718 ± 0.114 mm, P < .001). Also the global prevalence of carotid plaques was more frequent in men with ED (63.8% vs 44.8%, P < .001), even after adjusting by age, cardiovascular risk factors, and ongoing treatment (P = .039). Both the IMT and the prevalence of carotid plaques increased significantly with ED severity (P trend .004 and <.001, respectively). There were no significant differences between groups neither in mean ABI nor in the prevalence of subjects with ABI < 0.9. However, there was a trend to a lower ABI and a higher prevalence of ABI < 0.9 with increasing ED severity. CONCLUSION: In the general population, the presence of ED identifies subjects with higher atherosclerosis burden in carotid arteries but not in the lower extremities.

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish Society of Internal Medicine.

BACKGROUND: Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION: Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY: In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

Consensus on lipoprotein(a) of the Spanish Society of Arteriosclerosis. Literature review and recommendations for clinical practice. / Consenso sobre lipoproteína (a) de la Sociedad Española de Arteriosclerosis. Revisión bibliográfica y recomendaciones para la práctica clínica.

The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. Lp(a) concentration (especially very high levels) has an undeniable association with certain cardiovascular complications, such as atherosclerotic vascular disease (AVD) and aortic stenosis. However, there are several current limitations to both establishing epidemiological associations and specific pharmacological treatment. Firstly, the measurement of Lp(a) is highly dependent on the test used, mainly because of the characteristics of the molecule. Secondly, Lp(a) concentration is more than 80% genetically determined, so that, unlike other cardiovascular risk factors, it cannot be regulated by lifestyle changes. Finally, although there are many promising clinical trials with specific drugs to reduce Lp(a), currently only iPCSK9 (limited for use because of its cost) significantly reduces Lp(a). However, and in line with other scientific societies, the SEA considers that, with the aim of increasing knowledge about the contribution of Lp(a) to cardiovascular risk, it is relevant to produce a document containing the current status of the subject, recommendations for the control of global cardiovascular risk in people with elevated Lp(a) and recommendations on the therapeutic approach to patients with elevated Lp(a).

Use of combination therapy is associated with improved LDL-cholesterol management: 1-year follow-up results from the European observational SANTORINI study.

AIM: To assess whether implementation of the 2019 ESC/EAS dyslipidaemia guidelines observed between 2020-2021 improved between 2021-2022 in the SANTORINI study. METHODS: High- or very-high cardiovascular (CV) risk patients were recruited across 14 European countries from March 2020-February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. . RESULTS: Of 9559 patients enrolled, 9136 (2626 high risk, 6504 very high risk) had any follow-up data, and 7210 (2033 high risk, 5173 very high risk) had baseline and follow-up LDL-C data. LLT was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6% and 25.6% to 57.1% and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 mmol/L to 2.0 mmol/L. Goal attainment improved from 21.2% to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs 25.5%). CONCLUSIONS: LLT use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal, hence strategies are needed to improve implementation of combination LLT.

Cardiovascular diseases, a group of disorders of the heart and blood vessels, are the most common cause of death worldwide. Lowering low-density lipoprotein (LDL) cholesterol in the bloodstream reduces the risk of developing cardiovascular diseases, such as heart attacks and strokes. Guidelines recommend that those at highest risk of cardiovascular disease should achieve the lowest levels of LDL cholesterol. Several medications are available that help lower LDL cholesterol levels and prevent cardiovascular events, however, recent studies have shown that the majority of patients continue to have LDL cholesterol levels above optimal value in part due to suboptimal use of these medications. Here we report the results after 1 year of follow-up of the SANTORINI study (started in 2020) which aimed to document the management of LDL cholesterol in clinical practice across 14 countries in Europe. We found that better control of LDL cholesterol occurred when more than one drug was used (combination therapy). Use of combination therapy was low at the start of the study 25.6% but increased over 1 year to 37.9%, resulting in better control of LDL cholesterol at 1 year than observed at the start of the study. Nonetheless, only 31% of patients achieved their LDL cholesterol target levels based on the European guidelines. Greater use of combination therapies is needed in order to improve the overall population level control of LDL cholesterol.

Differences in the ankle-brachial index in the general population after 4 years of follow-up.

BACKGROUND: Variation in the ankle-brachial index (ABI) is related to the progression of atherosclerosis in the lower extremities and is associated with mid-term cardiovascular morbidity and mortality. The aim of this study was to investigate the changes in ABI after four years of follow-up of individuals in the general population, and the factors associated with relevant variations observed. PATIENTS AND METHODS: The study was performed in 750 volunteers (mean age 69.9 years) men without any evidence of peripheral artery disease, who attended a primary care centre. A complete physical examination, together with standard blood tests and ABI were performed. Four years later a new clinical evaluation was done. Variations in ABI values were considered relevant if > 10 %. RESULTS: Mean ABI in the second visit was 1.07 ± 0.15, which represented 0.02 ± 0.12 points lower than in the first visit (P < 0.001). Of these subjects, 157 (21.6 %) had an ABI decrease > 10 %. Multivariate analysis showed that the change was associated with male gender, cardiovascular history, no intake of blockers of the renin-angiotensin system, and the presence of atherogenic dyslipidaemia. A relevant increase in ABI was observed in 117 subjects (16.1 %), but was not associated with any of the studied factors. CONCLUSIONS: ABI values tend to decrease in the general population, although one sixth of the studied subjects had a relevant increase in this parameter.

Functional foods and nutraceuticals in the treatment of hypercholesterolemia: Statement of the Spanish Society of Arteriosclerosis 2023. / Alimentos funcionales y nutracéuticos en el tratamiento de la hipercolesterolemia: posicionamiento de la Sociedad Española de Arteriosclerosis 2023.

In the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance. (2) Hypolipidemic treatment «a la carte¼ in individuals in primary prevention. (3) Long-term cardiovascular prevention in individuals with no indication for lipid-lowering therapy. (4) Patients with optimized lipid-lowering treatment who do not achieve therapeutic objectives.

[HDL-cholesterol concentration and risk of SARS-CoV-2 infection in people over 75 years of age: a cohort with half a million participants from the Community of Madrid]. / Concentración de colesterol-HDL y riesgo de infección por SARS-CoV-2 en personas mayores de 75 años: una cohorte con medio millón de participantes de la Comunidad de Madrid.

OBJECTIVE: The aim of this study was to analyze the relationship between HDL-cholesterol and the risk of SARS-CoV-2 infection in over 75-year-olds residing in the Community of Madrid. METHODS: Study of a population-based cohort, composed of all residents in Madrid (Spain) born before January 1, 1945 and alive on December 31, 2019. Demographic, clinical and analytical data were obtained from primary care electronic medical records from January 2015. Confirmed SARS-CoV-2 infection was defined as a positive RT-PCR or antigen test result. Infection data correspond to the period March 1, 2020 through December 31, 2020. RESULTS: Of the 593,342 cohort participants, 501,813 had at least one HDL-cholesterol determination in the past 5 years. Their mean age was 83.4±5.6 years and 62.4% were women. A total of 36,996 (7.4%) had a confirmed SARS-CoV2 infection during 2020. The risk of infection [odds ratio (95% confidence interval)] for SARS-CoV2 according to increasing quintiles of HDL-cholesterol was 1, 0.960 (0.915-1.007), 0.891 (0.848-0.935), 0.865 (0.824-0.909) and 0.833 (0.792-0.876), after adjusting for age, sex, cardiovascular risk factors and comorbidities. CONCLUSIONS: There is an inverse and dose-dependent relationship between HDL-cholesterol concentration and the risk of SARS-CoV2 infection in subjects aged over 75 years of age in the Community of Madrid.

Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study.

Background: European data pre-2019 suggest statin monotherapy is the most common approach to lipid management for preventing cardiovascular (CV) events, resulting in only one-fifth of high- and very high-risk patients achieving the 2019 ESC/EAS recommended low-density lipoprotein cholesterol (LDL-C) goals. Whether the treatment landscape has evolved, or gaps persist remains of interest. Methods: Baseline data are presented from SANTORINI, an observational, prospective study that documents the use of lipid-lowering therapies (LLTs) in patients ≥18 years at high or very high CV risk between 2020 and 2021 across primary and secondary care settings in 14 European countries. Findings: Of 9602 enrolled patients, 9044 with complete data were included (mean age: 65.3 ± 10.9 years; 72.6% male). Physicians reported using 2019 ESC/EAS guidelines as a basis for CV risk classification in 52.0% (4706/9044) of patients (overall: high risk 29.2%; very high risk 70.8%). However, centrally re-assessed CV risk based on 2019 ESC/EAS guidelines suggested 6.5% (308/4706) and 91.0% (4284/4706) were high- and very high-risk patients, respectively. Overall, 21.8% of patients had no documented LLTs, 54.2% were receiving monotherapy and 24.0% combination LLT. Median (interquartile range [IQR]) LDL-C was 2.1 (1.6, 3.0) mmol/L (82 [60, 117] mg/dL), with 20.1% of patients achieving risk-based LDL-C goals as per the 2019 ESC/EAS guidelines. Interpretation: At the time of study enrolment, 80% of high- and very high-risk patients failed to achieve 2019 ESC/EAS guidelines LDL-C goals. Contributory factors may include CV risk underestimation and underutilization of combination therapies. Further efforts are needed to achieve current guideline-recommended LDL-C goals. Trial registration: ClinicalTrials.gov Identifier: NCT04271280. Funding: This study is funded by Daiichi Sankyo Europe GmbH, Munich, Germany.

HDL-cholesterol concentration and risk of SARS-CoV-2 infection in people over 75 years of age: a cohort with half a million participants from the Community of Madrid. / Concentración de colesterol-HDL y riesgo de infección por SARS-CoV-2 en personas mayores de 75 años: una cohorte con medio millón de participantes de la Comunidad de Madrid.

OBJECTIVE: The aim of this study was to analyze the relationship between HDL-cholesterol and the risk of SARS-CoV-2 infection in over 75-year-olds residing in the Community of Madrid. METHODS: Study of a population-based cohort, composed of all residents in Madrid (Spain) born before January 1, 1945 and alive on December 31, 2019. Demographic, clinical and analytical data were obtained from primary care electronic medical records from January 2015. Confirmed SARS-CoV-2 infection was defined as a positive RT-PCR or antigen test result. Infection data correspond to the period March 1, 2020 through December 31, 2020. RESULTS: Of the 593,342 cohort participants, 501,813 had at least one HDL-cholesterol determination in the past 5 years. Their mean age was 83.4±5.6 years and 62.4% were women. A total of 36,996 (7.4%) had a confirmed SARS-CoV2 infection during 2020. The risk of infection [odds ratio (95% confidence interval)] for SARS-CoV2 according to increasing quintiles of HDL-cholesterol was 1, 0.960 (0.915-1.007), 0.891 (0.848-0.935), 0.865 (0.824-0.909) and 0.833 (0.792-0.876), after adjusting for age, sex, cardiovascular risk factors and comorbidities. CONCLUSIONS: There is an inverse and dose-dependent relationship between HDL-cholesterol concentration and the risk of SARS-CoV2 infection in subjects aged over 75 years of age in the Community of Madrid.

Pre-infection HDL-cholesterol levels and mortality among elderly patients infected with SARS-CoV-2.

BACKGROUND AND AIMS: Low HDL-cholesterol (HDLc) concentration is associated with a greater risk of infection-related mortality. We wanted to evaluate the relationship between pre-infection HDLc levels and mortality among older patients infected with SARS-Cov-2. METHODS: This is a population-based, cohort study, comprising all individuals residing in Madrid (Spain) born before 1 January 1945, and alive on 31 December 2019. Demographic, clinical, and analytical data were obtained from the primary care electronic clinical records. Confirmed SARS-CoV-2 infection was defined as a positive result in the RT-qPCR or in the antigen test. A death from COVID-19 was defined as that registered in the hospital chart, or as any death occurring in the 15 days following a confirmed SARS-CoV-2 infection. Data on infection, hospitalization, or death due to SAR-CoV-2 were collected from 1 March 2020 through 31 December 2020. RESULTS: Of the 593,342 individuals comprising the cohort, 36,966 had a SARS-CoV-2 infection during 2020, and at least one HDLc measurement in the previous five years. Among them, 9689 (26.2%) died from COVID-19. After adjustment for age and sex, the relative risk (95% confidence interval) of COVID-19 death across increasing quintiles of HDLc was 1.000, 0.896 (0.855-0.940), 0.816 (0.776-0.860), 0.758 (0.719-0.799), and 0.747 (0.708-0.787). The association was maintained after further adjustment for comorbidities, statin treatment and markers of malnutrition. While in females this association was linear, in males it showed a U-shaped curve. CONCLUSIONS: In older subjects, a higher HDLc measured before SARS-CoV-2 infection was associated with a lower risk of death.

Glycemic variability and all-cause mortality in a large prospective southern European cohort of patients with differences in glycemic status.

BACKGROUND: Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). METHODS: Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality. RESULTS: A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of follow-up, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26-1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15-1.73); T2DM, HR = 1.36 (1.10-1.67). CONCLUSION: We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia.

Evaluation of contemporary treatment of high- and very high-risk patients for the prevention of cardiovascular events in Europe - Methodology and rationale for the multinational observational SANTORINI study.

Background and aims: Clinical practice before 2019 suggests a substantial proportion of high and very high CV risk patients taking lipid-lowering therapy (LLT) would not achieve the new LDL-C goals recommended in the 2019 ESC/EAS guidelines (<70 and < 55 mg/dL, respectively). To what extent practice has changed since the last ESC/EAS guideline update is uncertain, and quantification of remaining implementation gaps may inform health policy. Methods: The SANTORINI study is a multinational, multicentre, prospective, observational, non-interventional study documenting patient data at baseline (enrolment) and at 12-month follow-up. The study recruited 9606 patients ≥18 years of age with high and very high CV risk (as assigned by the investigators) requiring LLT, with no formal patient or comparator groups. The primary objective is to document, in the real-world setting, the effectiveness of current treatment modalities in managing plasma levels of LDL-C in high- and very high-risk patients requiring LLT. Key secondary effectiveness objectives include documenting the relationship between LLT and levels of other plasma lipids, high-sensitivity C-reactive protein (hsCRP) and overall predicted CV risk over one year. Health economics and patient-relevant parameters will also be assessed. Conclusions: The SANTORINI study, which commenced after the 2019 ESC/EAS guidelines were published, is ideally placed to provide important contemporary insights into the evolving management of LLT in Europe and highlight factors contributing to the low levels of LDL-C goal achievement among high and very high CV risk patients. It is hoped the findings will help enhance patient management and reduce the burden of ASCVD in Europe.

Overall Mortality and LDL Cholesterol Reduction in Secondary Prevention Trials of Cardiovascular Disease.

Pooled data from randomized clinical trials on lipid-lowering therapy have provided valuable information and clinical insights. Although cardiovascular disease is a common cause of death, mortality data have rarely been prominent in key lipid trials. The 4S, LIPID and HPS trials were the first to demonstrate a reduction in overall mortality. Lower- versus higher-intensity statin trials and non-statin lipid-lowering trials with ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors proved that additional lipid lowering significantly reduces the occurrence of cardiovascular events. However, only the ODYSSEY OUTCOMES trial showed a reduction in all-cause mortality. The aim of the present narrative review was to contrast these results with those of other key lipid trials: those assessing statins compared with placebo, those evaluating intensive- versus moderate-intensity lipid-lowering therapy and, finally, those investigating non-statin lipid-lowering therapies.

Clinical course and prognostic factors of COVID-19 infection in an elderly hospitalized population.

INTRODUCTION: Older subjects have a higher risk of COVID-19 infection and a greater mortality. However, there is a lack of studies evaluating the characteristics of this infection at advanced age. PATIENTS AND METHODS: We studied 404 patients ≥ 75 years (mean age 85.2 ±â€¯5.3 years, 55 % males), with PCR-confirmed COVID-19 infection, attended in two hospitals in Madrid (Spain). Patients were followed-up until they were discharged from the hospital or until death. RESULTS: Symptoms started 2-7 days before admission, and consisted of fever (64 %), cough (59 %), and dyspnea (57 %). A total of 145 patients (35.9 %) died a median of 9 days after hospitalization. In logistic regression analysis, predictive factors of death were age (OR 1.086; 1.015-1.161 per year, p = 0.016), heart rate (1.040; 1.018-1.061 per beat, p < 0.0001), a decline in renal function during hospitalization (OR 7.270; 2.586-20.441, p < 0.0001) and worsening dyspnea during hospitalization (OR 73.616; 30.642-176.857, p < 0.0001). Factors predicting survival were a female sex (OR 0.271; 0.128-0.575, p = 0.001), previous treatment with RAAS inhibitors (OR 0.459; 0.222-0.949, p = 0.036), a higher oxygen saturation at admission (OR 0.901; 0.842-0.963 per percentage point increase, p = 0.002), and a greater platelet count (OR 0.995; 0.991-0.999 per 106/L, p = 0.025). CONCLUSION: Elderly patients with COVID-19 infection have a similar clinical course to younger individuals. Previous treatment with RAAS inhibitors, and demographic, clinical and laboratory data influence prognosis.

Phenotype of haptoglobin and presence of subclinical vascular disease: Population study. / Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional.

INTRODUCTION AND OBJECTIVES: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. PATIENTS AND METHODS: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. RESULTS: Of the 1,256 participants included in the present analysis (mean age 61.6±6years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P<.0001) and arterial hypertension (39.2% vs. 32.2%, P=.012), and they more frequently received treatment with statins (31.5% vs 21.6%, P<.0001), and with antihypertensive agents (38.4% vs 30.8%, P=.006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P=.011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95%CI 1.01-1.70, P=.044). CONCLUSION: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

Prevalence of carotid stenosis and silent myocardial ischemia in asymptomatic subjects with a low ankle-brachial index.

OBJECTIVE: Subjects with symptomatic peripheral artery disease (PAD) have an elevated prevalence of carotid stenosis and of silent myocardial ischaemia. As such, clinical guidelines advocate the detection of sub-clinical vascular disease in this population. However, the prevalence of occult vascular disease in asymptomatic patients with a low ankle-brachial index (ABI) has not been previously evaluated. METHODS: Cross-sectional study in five primary care centres for patients' selection and two University Hospitals for further assessment. Subjects were 1070 asymptomatic individuals between 60 and 80 years of age with at least two cardiovascular risk factors, selected for ankle-brachial index measurement. Eighty five subjects with an ABI <0.9 and an equal number of controls, matched for age, gender, diabetes, and smoking habit, and with a normal ABI, were referred to the Hospital for carotid ultrasound and exercise stress tests (EST). Main outcome measures were prevalence of a carotid stenosis >50% and an abnormal EST. RESULTS: The prevalence of a low ABI in the overall population was 9.1%. A carotid stenosis >50% was detected in 14.3% of the subjects with a low ABI and in 4.7% of the control subjects (Odds Ratio [OR]: 3.37; 95% Confidence Interval [CI]: 1.04-10.93, P = .033). The prevalence of a positive EST test was 16.2% in those with a low ABI and 10.5% in control subjects (OR: 1.65; 95% CI: 0.63-4.29, P = .309). These prevalences were higher in older subjects, in those with hypertension or diabetes, or in those with dyslipidemia. CONCLUSION: Our results indicate that in high-risk asymptomatic subjects >60 years of age, the presence of an ABI <0.9 identifies a subgroup of the population with an increased prevalence of carotid stenosis and of silent myocardial ischemia and, as such, are candidates for closer follow-up.

Factors associated with the discontinuation of evidence-based cardiovascular therapies in patients with stable coronary artery disease: a primary care perspective.

BACKGROUND: To identify factors associated with the discontinuation of evidence-based cardiovascular therapies after hospital discharge for a coronary event. DESIGN: Cross-sectional study carried out between June and October 2004 in 1799 primary care centers throughout Spain. PATIENTS AND METHODS: Eight thousand eight hundred and seventeen patients (73.7% males; 65.4 years) admitted for coronary disease causes in the past 6 months to 10 years and attending primary care postdischarge from hospital. Current medications, those prescribed at hospital discharge, and the development of adverse events, new risk factors, and comorbidities during follow-up, were collected from clinical records. RESULTS: After a median follow-up of 37.4 months, discontinuation rate of lipid-lowering agents, angiotensin renin system blockers, antiplatelet drugs, and beta-blockers were 7.2, 9.1, 10, and 20%, respectively. Of these, 10.8, 16.5, 9.9, and 20.1%, respectively, were because of adverse events. Factors associated with the discontinuation of lipid-lowering agents were the development of hypertension and diabetes during the follow-up. Discontinuation of antiplatelet drug was associated with an earlier history, or with de-novo occurrence, of atrial fibrillation. Discontinuation of angiotensin renin system blockers was associated with the development of atrial fibrillation, diabetes and hypercholesterolemia, and discontinuation of beta-blockers with de-novo appearance of peripheral artery disease, cerebrovascular disease, and heart failure. CONCLUSION: In patients followed-up in primary care, the discontinuation rate of cardiovascular disease medications was low and was mainly related to the development of adverse events together with new risk factors and comorbidities arising after hospital discharge.

Patients at high risk of cerebrovascular disease: the REACH study.

Cerebrovascular disease is one of the leading causes of morbidity and mortality in developed countries. The identification of at-risk individuals is a high priority so that efficacious preventive measures can be implemented. Subjects with the highest risk of cerebrovascular diseases are those who already have had a stroke or a transient ischemic attack, and those with vascular disease in other territories, either in coronary or peripheral arteries. Other subjects at risk are those with cardiac disease, such as atrial fibrillation, those with hypertension, diabetes and smoking habit, as well as individuals with subclinical vascular disease. Although there is considerable evidence for the efficacy of preventive treatment in this population, the percentage of patients receiving optimum treatment is far from ideal. There is a need to implement strategies in the population directed towards increasing awareness of the need to establish healthy habits and adequate preventive pharmacological treatment that could reduce the incidence of this debilitating disease.