SEA 2024 Standards for Global Control of Vascular Risk. / Estándares de la Sociedad Española de Arteriosclerosis 2024 para el control global del riesgo vascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

Modified SADI-S in non-obese diabetic rats: Description of the surgical technique.

Background: Single anastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S) is a predominantly malabsorptive technique that has shown excellent results in morbid obese patients. The aim of this study is to establish a rodent model modifying the SADI-S technique by performing a proximal duodenojejunal anastomosis. This model can be useful for the study of glucose metabolism without malabsorption observed after the SADI-S technique. Methods: Goto-Kakizaki rats, a genetic model of non-obese and non-hypertensive type 2 diabetes mellitus, that develop hyperglycemia at an early age was used. Surgery consisted in a sleeve gastrectomy, duodenojejunal anastomosis and duodenal exclusion using three different techniques: duodenal transection (DT), duodenal ligation with hem-o-lock (DLH), and duodenal ligation with suture (DLS). Surgery time, weight loss, morbidity and mortality were recorded. Results: A total of 16 animals were subjected to surgical intervention and overall mortality was 25 %, with the DT group showing the highest mortality rate (42.9 %). No differences were observed among groups in terms of weight loss. Conclusion: The surgical technique described in this work is feasible and reproducible. Weight loss is comparable regardless of the technique used for duodenal exclusion.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Management of Persistent SARS-CoV-2 Infection in Patients with Follicular Lymphoma.

INTRODUCTION: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying hematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of 5 patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. METHODS: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids, and convalescent plasma in 5 patients with FL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistent infection. Reverse transcriptase polymerase chain reaction tests and peripheral blood immunophenotype were performed for all patients. RESULTS: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13-42) from the previous discharge. They all showed B-cell depletion by immunophenotyping, and no traces of immunoglobulin antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. CONCLUSION: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed FL patients treated with ICT.

Clinical profile of patients treated with evolocumab in lipid/internal medicine units of Spain. Observational study (RETOSS-IMU). / Perfil clínico de los pacientes tratados con evolocumab en unidades de lípidos/medicina interna en España. Estudio observacional (RETOSS-IMU).

OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy, and the effects of treatment in the initial phase of evolocumab availability in lipid/internal medicine units in Spain. METHODS: Retrospective, observational study, based on the medical records of consecutive patients initiating treatment with evolocumab (from February 2016 to July 2017) in 20 internal medicine units in Spain. A review was made of the demographic and clinical characteristics of the patients, the lipid lowering treatment, and the evolution of the lipid profiles between 12weeks pre-initiation and 12±4weeks post-initiation of evolocumab. RESULTS: A total of 136 patients were analysed, of whom 64.0% were men, and the mean age (standard deviation, SD) was 56.6 (11.5) years. The large majority (75%) had familial hypercholesterolaemia (4 homozygous), and 51.0% of them had suffered at least one cardiovascular event. Atherosclerotic cardiovascular disease (ASCVD) was present in 61% of all patients. At initiation of evolocumab, 61.0% of the patients were taking high-intensity statins, and 60.3% were receiving ezetimibe. The mean (and SD) of LDL-C levels at initiation of evolocumab was 169.1 (56.6) mg/dL. The LDL-C was greater than 160mg/dL in 46.4% of patients, and ≥190mg/dL in 26.5%. During the observation period, evolocumab produced significant reductions in LDL-C of 55.7% (P<.0001), achieving mean values of 74.3mg/dL. At week12, more than half (53.8%) of patients achieved LDL-C levels <70mg/dL, and 26.9% <50mg/dL. CONCLUSIONS: In the lipid/internal medicine units, evolocumab was mainly prescribed in patients with familial hypercholesterolaemia, with or without ASCVD. The initial use of evolocumab was in accordance with the guidelines of the Spanish Society of Arteriosclerosis (SEA) of 2016, with LDL-C levels being well above the recommended thresholds for treatment initiation. Evolocumab treatment in clinical practice reduced LDL-C levels by about 55%, a similar reduction to that reported in clinical trials. Most patients achieved LDL-C goals.

Toward a new clinical classification of patients with familial hypercholesterolemia: One perspective from Spain.

The introduction of singular therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification of patients eligible for intensive lipid lowering therapy. According to the European Medicines Administration, PCSK9i are recommended in primary prevention only in familial hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic issue, because it has many clinical implications. The bases of a diagnosis of FH are not entirely clear. The availability of genetic testing, including large genome-wide association analyses and whole genome studies, has shown that some patients with a clinical diagnosis of definite FH have no mutations in the genes associated with the disease. This fact does not exclude the very high cardiovascular risk of these patients, and an early and intensive lipid lowering therapy is recommended in all FH patients. Because an FH diagnosis is a cornerstone for decisions about therapies, a precise definition of FH is urgently required. This is an expert consensus document from the Spanish Atherosclerosis Society. We propose the following classification: familial hypercholesterolemia syndrome integrated by (1) heterozygous familial hypercholesterolemia: patients with clinically definite FH and a functional mutation in one allele of the LDLR, ApoB:100, and PCSK9 genes; (2) homozygous familial hypercholesterolemia: mutations affect both alleles; (3) polygenic familial hypercholesterolemia: patients with clinically definite FH but no mutations associated with FH are found (to be distinguished from non-familial, multifactorial hypercholesterolemia); (4) familial hypercholesterolemia combined with hypertriglyceridemia: a subgroup of familial combined hyperlipidaemia patients fulfilling clinically definite FH with associated hypertriglyceridemia.

Indications of PCSK9 inhibitors in clinical practice. Recommendations of the Spanish Sociey of Arteriosclerosis (SEA), 2019. / Indicaciones de los inhibidores de PCSK9 en la práctica clínica. Recomendaciones de la Sociedad Española de Arteriosclerosis (SEA), 2019.

A group of experts convened by the Spanish Society of Arteriosclerosis (SEA) has been in charge of updating the SEA document on the indications of PCSK9 inhibitors (PCSK9i) in clinical practice that was published in 2016. This update is justified by the fact that the data from clinical trials carried out on a large scale with PCSK9i have shown that in addition to their high potency to lower atherogenic cholesterol, they reduce the risk of atherosclerotic cardiovascular disease, both in patients with stable disease, and with recent disease, and with a high degree of security. This update provides the recommendations and level of evidence for the prescription of iPCSK9 in patients with homozygous and heterozygous familial hypercholesterolemia, with atherosclerotic cardiovascular disease, and in primary prevention in patients with very high cardiovascular risk. These recommendations have been established taking into account the concentration of LDL-C, the clinical situation of the patient, the additional risk factors and the cost-effectiveness of their use.

Use of the cardiovascular polypill 40mg in secondary cardiovascular prevention. / Uso de la polipíldora cardiovascular 40mg en prevención cardiovascular secundaria.

Controlling cardiovascular risk factors (CV) is essential for patients with cardiovascular disease. The CV polypill contains aspirin 100mg, atorvastatin 20mg or 40mg, and ramipril 2.5mg, 5mg or 10mg in a fixed combination pill. The objective was to review the evidence on the secondary prevention of cardiovascular disease, to establish the eventual patient profiles suitables to consider the use of CV polypill with atorvastatin 40mg in secondary CV prevention (P40PS), and to define the priority situations most adequate for the use of P40PS. A bibliographic review was carried out, which was complemented with the clinical opinion of 19 specialists. During hospitalization and discharge, P40PS is an option for patients admitted because of an atherothrombotic event, peripheral arterial disease, or other causes, and with the indication of the monocomponents. Its priority use is proposed in: prior intolerance to the highest dose of atorvastatin (80mg), age>75 years, low weight, stage 3 of chronic renal failure, hypothyroidism, drug interactions and Asian origin. Outside the hospital setting, the P40PS is a therapeutic alternative in patients with a need for secondary CV prevention and with indication to receive the monocomponents. The priority situations to receive the P40PS are: to be taking the three components separately, to require polypharmacy, lack of adherence or understanding of the treatment, and lack of control of CV risk factors. This work is the first with proposals for the use of P40PS and can facilitate the treatment of patients with cardiovascular disease in secondary prevention.

[Lower limb arterial disease and renal artery stenosis]. / Arteriopatía de las extremidades inferiores y estenosis de las arterias renales.

Peripheral arterial disease (PAD) refers to the atherosclerotic involvement of non-coronary and extracranial arteries, including visceral arteries, the aorta and its branches and the arteries of the limbs. PAD usually refers exclusively to atherosclerosis of the limbs (in particular the lower limbs). Age, male sex, smoking and diabetes, as well as hypertension and dyslipidemia, are the most relevant risk factors for the development of PAD. PAD is frequently associated with coronary heart disease and stroke. PAD patients have increased risk of developing cardiovascular complications (coronary disease, stroke) and total and cardiovascular mortality, even after adjustment by conventional risk factors. Despite this PAD exhibit a worse control of risk factors. This opens up an important opportunity to optimize their control, which can result in an improvement of the prognosis of patients with PAD. Ischemic nephropathy includes a constellation of disorders that are frequently associated: hypertension, renal failure and renal artery stenosis (RAS). RAS risk factors are similar to those of PAD. Recent studies have shown that renal revascularization is not associated with improvement in blood pressure control, preservation of renal function or reduction of cardiovascular events in most patients. Therefore, revascularization should be reserved for selected cases on an individual basis. In all cases, a strict control of vascular risk factors should be attempted.

[Dyslipemia in diabetics treated with statins. Results of the DYSIS study in Spian]. / Dislipemia en población diabética tratada con estatinas. Resultados del estudio DYSIS en España.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (DM2) is characterized by carrying a high cardiovascular risk. This situation underscores the importance of intensively treating the risk factors present in diabetic patients, notably dyslipemia. The treatment with cholesterol-lowering drugs may be especially effective to reduce the cardiovascular risk in diabetic patients. Therefore, LDL-cholesterol is a priority target in the lipid management of these patients. This study analyzes the alterations in the lipid profile of diabetic patients receiving treatment with statins, which therefore may contribute to persistent cardiovascular risk in such individuals. PATIENTS AND METHODS: The DYSIS (Dyslipidemia International Study) is an international, observational trial analyzing the lipid profile of patients treated with statins and followed-up on in outpatient clinics by primary care physicians and specialists. This study is referred to the data on the diabetic patients. RESULTS: Of the total patients enrolled in the DYSIS, the present study included 3703 patients, 39% being diabetics. A total of 59.2% of diabetics showed LDL-C out of goal; triglyceride elevation was observed in 43.6% and 36.4% showed low HDL-C. In diabetics patients with coronary heart disease, 31% had uncontrolled levels of all three lipid parameters. The prevalence of out of goal LDL-C in diabetic patients with metabolic syndrome was close to 60%; 39.8% had low levels of HDL-C and 46,6% high levels of triglycerides. In addition, 57% of diabetic patients with obesity showed LDL-C out of control, despite statins treatment. CONCLUSIONS: Cardiovascular diseases remain the main cause of morbidity-mortality in patients with DM2. The results of the present study show that in diabetic patients the degree of control is very limited with regard to LDL-cholesterol. More than half of diabetic patients treated with statins had LDL-cholesterol out of goal. The level of dyslipidemia control was low, despite statins treatment. Therefore, the detection of atherogenic dyslipidemia may point to the advisability of using combination therapy for dyslipidemia in diabetic patients.

Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment.

We report a patient with inappropriate secretion of thyrotropin (TSH) and a pituitary mass. Although she had been treated for biochemical hyperthyroidism with thyroid surgery and radioiodine ablation, she had never complained of specific symptoms or demonstrated signs of overt thyroid dysfunction. On evaluation, she had increased free thyroxine and TSH levels, normal serum glycoprotein alpha-subunit levels, and a significant TSH over-response to exogenous thyrotropin-releasing hormone stimulation. Magnetic resonance imaging with gadolinium enhancement showed a pituitary enlargement with suprasellar extension. An indium In 111 pentetreotide scan showed an abnormal focus of radionuclide accumulation in the pituitary area. Sequencing of the TRbeta gene showed that the patient was heterozygous for a new single nucleotide substitution resulting in the replacement of the normal arginine with a serine at amino acid 320 (R320S). We review the difficulties encountered in establishing a correct diagnosis in patients with inappropriate secretion of TSH in combination with pituitary enlargement. Due to its possible false-negative results, we do not recommend the use of indium In 111 pentetreotide as a tool in the differential diagnosis of inappropriate secretion of TSH.

[Similarities and differences among patients with symptomatic atherosclerosis affecting several territories. The AIRVAG cohort (Integral Attention to Global VAscular Risk)]. / Similitudes y diferencias entre los pacientes con aterosclerosis sintomática de distintos territorios. Cohorte AIRVAG (Atención Integral al Riesgo VAscular Global).

BACKGROUND AND OBJECTIVE: Even though atherosclerosis is a systemic disease, few prospective studies have evaluated in a thorough and systematic manner the whole vascular tree in patients with clinical damage of different territories. PATIENTS AND METHOD: Prospective protocolized study of 269 consecutive patients younger than 70, attended because of symptomatic arteriosclerosis of any territory -53% coronary (CHD), 32% cerebrovascular (CVD), 15% peripheral (PVD)-. Patients underwent evaluation of risk factors and their control, systematic non-invasive study of the vascular tree (Doppler-ultrasound) and comparison between groups according to the index territory. RESULTS: Even though all risk factors were represented in the 3 groups, male sex, smoking and diabetes were more frequent in PVD and dyslipemia was more common in CHD (p < 0.05) Abdominal aortic diameter and carotid intima-media thickness were similar for all groups, while the number of carotid plaques was higher in PVD. CHD patients more often presented left ventricular hypertrophy and reduced ejection fraction. PVD patients showed a marked reduction of the ankle-brachial index as well as increased C-reactive protein and homocysteine (p < 0.05). Severe unsuspected vascular lesions were found in 13% of cases (95% confidence interval, 9.5-17.6%). Risk factor control was better for CHD, followed by CVD and PVD, but was globally poor. CONCLUSIONS: The systematic evaluation of the vascular tree detects generalized atherosclerotic lesions, in some cases severe and clinically unsuspected. New markers to identify patients at very high risk are necessary. Peripheral vascular disease identifies a group of patients of particular risk. Risk factor control is deficient, particularly among PVD patients.

[Underrecognized peripheral arterial disease in patients with acute coronary syndrome: prevalence of traditional and emergent cardiovascular risk factors]. / Enfermedad arterial periférica desconocida en pacientes con síndrome coronario agudo: prevalencia y patrón diferencial de los factores de riesgo cardiovascular tradicionales y emergentes.

INTRODUCTION AND OBJECTIVES: Peripheral arterial disease (PAD) frequently coexists with coronary artery disease. Our objective was to determine the prevalence of traditional and emergent cardiovascular risk factors in patients with acute coronary syndrome (ACS), with or without PAD. PATIENTS AND METHOD: A prospective study of 141 consecutive patients (< 70 years old) admitted to our hospital with ACS was performed. PAD was diagnosed when the ankle-brachial index (ABI) was < or = 0.9. Traditional cardiovascular risk factors were evaluated. C-reactive protein, homocysteine, amyloid A, lipoprotein (a), fibrinogen, apolipoprotein A1, and apolipoprotein B100 serum levels, and microalbuminuria were measured. Specific genotypes were also determined. RESULTS: Patients were divided into two groups according to whether PAD was present (37 patients, 26% of total, ACS-PAD group) or absent (104 patients, ACS group). In the ACS-PAD group, patients were older, and diabetes and hypertension were significantly more common. Moreover, levels of C-reactive protein (3.1 mg/L vs 2.18 mg/L; P<.05), homocysteine (11.45 mmol/L vs 9.4 mmol/L; P<.01), amyloid A (5.2 mg/mL vs 3.7 mg/mL; P<.05), and microalbuminuria (4.89 mg/L vs 3.1 mg/L; P<.05) were significantly higher in this group. Logistic regression analysis showed that poorly controlled diabetes (OR = 6.3; 95% CI, 1.1-36.7), time-dependent tobacco exposure (OR = 1.5 per decade; 95% CI, 1.2-2.0), and high pulse pressure (OR = 1.9 per 10 mmHg; 95% CI, 1.3-2.7) were independent predictors of the presence of PAD. CONCLUSIONS: Several traditional and emergent cardiovascular risk factors were more prevalent in patients with acute coronary syndrome and peripheral arterial disease. Moreover, some factors were independent predictors of peripheral arterial disease.