Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes.

BACKGROUND: The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). METHODS: We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. RESULTS: The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87-101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. CONCLUSION: A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

Age, Origin and Functional Study of the Prevalent LDLR Mutation Causing Familial Hypercholesterolaemia in Gran Canaria.

The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110-1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant.

Ex vivo evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis.

AIM: To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an ex vivo model of gastro-oesophageal reflux. METHODS: An ex vivo evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000U/mL). RESULTS: The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (p<0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% vs. 18.9 (12.3)% for the control (p<0.05). In addition, after 30min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution. CONCLUSIONS: Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this ex vivo model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.

Estrategias de tratamiento de las dislipemias en prevención primaria y secundaria. Registro de la Sociedad Española de Arteriosclerosis / Dyslipidemia treatment strategies in primary and secondary prevention. Dyslipemia Registry of the Spanish Arteriosclerosis Society

Introducción: Los estudios clínicos reflejan que los pacientes con riesgo cardiovascular elevado todavía están lejos de alcanzar los objetivos terapéuticos, especialmente de los niveles de cLDL. Si el manejo de estos pacientes en unidades especializadas difiere de otros escenarios no es conocido. Pacientes y métodos: Se seleccionaron 61 Unidades de Lípidos certificadas en el Registro de Dislipemias de la Sociedad Española de Arteriosclerosis para la recogida de datos del estudio. Se incluyeron 3.58 sujetos > 18 años que cumplían los criterios de hipercolesterolemia (colesterol LDL ≥ 160 mg/dL o colesterol no HDL ≥ 190 mg/dL) sin hipercolesterolemia familiar. Un total de 1.665 sujetos fueron estudiados con un tiempo medio de seguimiento de 4,2 años. Resultados y conclusiones: Un total de 42 sujetos tuvieron un evento cardiovascular desde su inclusión en el Registro, que supone 0,6%. No hubo diferencias en el tratamiento utilizado al inicio del seguimiento entre los sujetos con y sin evento prospectivo. El cLDL mejoró durante el seguimiento, pero 50% de los pacientes no alcanzaron los objetivos terapéuticos en la visita final del seguimiento. Se observó un aumento del uso de tratamiento hipolipemiante de alta potencia, incluyendo los inhibidores de PCSK9 en un 16,7% de los sujetos con recurrencias.(AU)

Introduction: Clinical studies show that patients with high cardiovascular risk are still far from reaching the therapeutic objectives, especially of the levels of LDL cholesterol. If the management of these patients in specialized units differs from other scenarios is known. Patients and methods: 61 certified Lipid Units were selected in the Registry of Dyslipemias of the Spanish Arteriosclerosis Society for the collection of study data. The study included 3958 subjects >18 years of age who met the criteria for hypercholesterolemia (LDL cholesterol ≥160 mg/dL or non-HDL cholesterol ≥190 mg/dL) without familial hypercholesterolemia. A total 1,665 subjects were studied with a mean follow-up time of 4.2 years. Results and conclusions: A total of 42 subjects had a cardiovascular event since their inclusion in the Registry, which represents 0.6%. There were no differences in the treatment used at follow-up, but 50% of the patients did not reach the therapeutic goals at the visit end of follow-up. An increase in the potency of the lipid-lowering treatment was observed, including PCSK9 inhibitors use in 16.7% of subjects with recurrences.(AU)

Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO).

BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS: 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2 (51.7% of patients had eGFR <60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c ≥160mg/dL and 29.3% ≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use remained stable. CONCLUSION: In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study.

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.

Dyslipidemia treatment strategies in primary and secondary prevention. Dyslipemia Registry of the Spanish Arteriosclerosis Society. / Estrategias de tratamiento de las dislipemias en prevención primaria y secundaria. Registro de la Sociedad Española de Arteriosclerosis.

INTRODUCTION: Clinical studies show that patients with high cardiovascular risk are still far from reaching the therapeutic objectives, especially of the levels of LDL cholesterol. If the management of these patients in specialized units differs from other scenarios is known. PATIENTS AND METHODS: 61 certified Lipid Units were selected in the Registry of Dyslipemias of the Spanish Arteriosclerosis Society for the collection of study data. The study included 3958 subjects >18 years of age who met the criteria for hypercholesterolemia (LDL cholesterol ≥160 mg/dL or non-HDL cholesterol ≥190 mg/dL) without familial hypercholesterolemia. A total 1,665 subjects were studied with a mean follow-up time of 4.2 years. RESULTS AND CONCLUSIONS: A total of 42 subjects had a cardiovascular event since their inclusion in the Registry, which represents 0.6%. There were no differences in the treatment used at follow-up, but 50% of the patients did not reach the therapeutic goals at the visit end of follow-up. An increase in the potency of the lipid-lowering treatment was observed, including PCSK9 inhibitors use in 16.7% of subjects with recurrences.

Leu22_Leu23 Duplication at the Signal Peptide of PCSK9 Promotes Intracellular Degradation of LDLr and Autosomal Dominant Hypercholesterolemia.

BACKGROUND: PCSK9 (Proprotein convertase subtilisin/kexin type 9) regulates LDL-C (low-density lipoprotein cholesterol) metabolism by targeting LDLr (LDL receptor) for lysosomal degradation. PCSK9 gain-of-function variants cause autosomal dominant hypercholesterolemia by reducing LDLr levels, the D374Y variant being the most severe, while loss-of-function variants are associated with low LDL-C levels. Gain-of-function and loss-of-function activities have also been attributed to variants occurring in the PCSK9 signal peptide. Among them, L11 is a very rare PCSK9 variant that seems to increase LDL-C values in a moderate way causing mild hypercholesterolemia. METHODS: Using molecular biology and biophysics methodologies, activities of L8 and L11 variants, both located in the leucine repetition stretch of the signal peptide, have been extensively characterized in vitro. RESULTS: L8 variant is not associated with increased LDLr activity, whereas L11 activity is increased by ≈20% compared with wt PCSK9. The results suggest that the L11 variant reduces LDLr levels intracellularly by a process resulting from impaired cleavage of the signal peptide. This would lead to less efficient LDLr transport to the cell membrane and promote LDLr intracellular degradation. CONCLUSIONS: Deletion of a leucine in the signal peptide in L8 variant does not affect PCSK9 activity, whereas the leucine duplication in the L11 variant enhances LDLr intracellular degradation. These findings highlight the importance of deep in vitro characterization of PCSK9 genetic variants to determine pathogenicity and improve clinical diagnosis and therapy of inherited familial hypercholesterolemia disease.

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism.

Familial hypercholesterolemia (FH) is a genetic disease characterized by high low-density lipoprotein (LDL) cholesterol (LDL-c) concentrations that increase cardiovascular risk and cause premature death. The most frequent cause of the disease is a mutation in the LDL receptor (LDLR) gene. Diabetes is also associated with an increased risk of cardiovascular disease and mortality. People with FH seem to be protected from developing diabetes, whereas cholesterol-lowering treatments such as statins are associated with an increased risk of the disease. One of the hypotheses to explain this is based on the toxicity of LDL particles on insulin-secreting pancreatic ß-cells, and their uptake by the latter, mediated by the LDLR. A healthy lifestyle and a relatively low body mass index in people with FH have also been proposed as explanations. Its association with superimposed diabetes modifies the phenotype of FH, both regarding the lipid profile and cardiovascular risk. However, findings regarding the association and interplay between these two diseases are conflicting. The present review summarizes the existing evidence and discusses knowledge gaps on the matter.

Hipercolesterolemia familiar en Gran Canaria: mutación con efecto fundador y alta frecuencia de diabetes / Familial hypercholesterolemia in Gran Canaria: Founder mutation effect and high frequency of diabetes

Introducción: Gran Canaria es una región de aislamiento genético para hipercolesterolemia familiar, debido a una mutación fundadora, p.[Tyr400_Phe402del], en el gen del receptor de LDL (LDLR). Datos iniciales indican que sus portadores podrían tener una alta prevalencia de diabetes. Material y métodos: Se reclutó a los pacientes mayores de 30 años con hipercolesterolemia familiar y mutación confirmada en LDLR en un hospital de tercer nivel de Gran Canaria y se comparó la prevalencia de diabetes y otros datos clínicos entre los portadores de p.[Tyr400_Phe402del] y los de otras mutaciones en LDLR. Resultados: El 76,4% de los 89 participantes era portador de p.[Tyr400_Phe402del]. En ese grupo la prevalencia de diabetes fue significativamente más alta (25 vs. 4%, p=0,045). Dichos casos también tenían mayor prevalencia de enfermedad cardiovascular y niveles más altos de colesterol LDL y triglicéridos. No hubo diferencias en edad, peso, índice de masa corporal, cintura, edad de inicio y tiempo de tratamiento con estatinas. Sin embargo, sí precisaban más a menudo inhibidores de PCSK9 (51,5 vs. 24%, p=0,027). Conclusiones: La mutación p.[Tyr400_Phe402del] se asocia a una elevada prevalencia de diabetes, no explicada por factores de riesgo clásicos, como la edad, la obesidad o el uso prolongado de estatinas.(AU)

Introduction: Gran Canaria is a region of genetic isolation of familial hypercholesterolemia due to a founder mutation, p. [Tyr400_Phe402del], in the LDL receptor (LDLR) gene. Initial data suggest that its carriers could have a high prevalence of diabetes. Material and methods: Patients over 30 years of age with familial hypercholesterolemia and a confirmed mutation in LDLR were recruited from a tertiary hospital in Gran Canaria. The prevalence of diabetes and other clinical data were compared among carriers of p. [Tyr400_Phe402del] and those with other LDLR mutations. Results: 76.4% of the 89 participants were carriers of p.[Tyr400_Phe402del]. The prevalence of diabetes in this group was significantly higher (25 vs. 4%, P=.045). These cases also had a higher prevalence of cardiovascular disease and higher levels of LDL cholesterol and triglycerides. There were no differences in age, weight, body mass index, waist, age of onset, and time of statin treatment. However, they required PCSK9 inhibitors more often (51.5 vs 24%, P=.027). Conclusions: The mutation p.[Tyr400_Phe402del] is associated with a high prevalence of diabetes, not explained by classic risk factors, such as age, obesity, or long-term use of statins.(AU)

Prehabilitation for Bariatric Surgery: A Randomized, Controlled Trial Protocol and Pilot Study.

Bariatric surgery is the most efficacious treatment for obesity, though it is not free from complications. Preoperative conditioning has proved beneficial in various clinical contexts, but the evidence is scarce on the role of prehabilitation in bariatric surgery. We describe the protocol and pilot study of a randomized (ratio 1:1), parallel, controlled trial assessing the effect of a physical conditioning and respiratory muscle training programme, added to a standard 8-week group intervention based on therapeutical education and cognitive-behavioural therapy, in patients awaiting bariatric surgery. The primary outcome is preoperative weight-loss. Secondary outcomes include associated comorbidity, eating behaviour, physical activity, quality of life, and short-term postoperative complications. A pilot sample of 15 participants has been randomized to the intervention or control groups and their baseline features and results are described. Only 5 patients completed the group programme and returned for assessment. Measures to improve adherence will be implemented and once the COVID-19 pandemic allows, the clinical trial will start. This is the first randomized, clinical trial assessing the effect of physical and respiratory prehabilitation, added to standard group education and cognitive-behavioural intervention in obese patients on the waiting list for bariatric surgery. Clinical Trial Registration: NCT0404636.

Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO). / Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España (RETOSS-NEFRO).

BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS: Sixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0)ml/min/1.73m2 (51.7% of patients had eGFR<60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9)mg/dL (53.4% of patients with LDL-c≥160mg/dL and 29.3%≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use were remained stable. CONCLUSION: In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins.

BACKGROUND: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. METHODS: This is an observational, multicenter, case-control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. RESULTS: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. CONCLUSION: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts.

Rapid decline of anti-SARS-CoV-2 antibodies in patients on haemodialysis: the COVID-FRIAT study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients on haemodialysis (HD) have high mortality. We investigated the value of reverse transcription polymerase chain reaction (RT-PCR) and the dynamic changes of antibodies (enzyme-linked immunosorbent assay immunoglobulin M (IgM) + IgA and/or IgG) in a large HD cohort. METHODS: We conducted a prospective observational study in 10 Madrid HD centres. Infection rate, anti-SARS-CoV-2 antibody dynamics and the incidence of asymptomatic SARS-CoV-2 infection (defined by positive RT-PCR, IgM + IgA and/or IgG) were assessed. RESULTS: From 1 March to 15 April 2020, 136 of 808 (16.8%) HD patients were diagnosed with symptomatic COVID-19 by RT-PCR of nasopharyngeal swabs and 42/136 (31%) died. In the second fortnight of April, RT-PCR and anti-SARS-CoV-2 antibodies were assessed in 763 of the surviving patients. At this point, 69/91 (75.8%) symptomatic COVID-19 patients had anti-SARS-CoV-2 antibodies. Four weeks later, 15.4% (10/65) of initially antibody-positive patients had become negative. Among patients without prior symptomatic COVID-19, 9/672 (1.3%) were RT-PCR positive and 101/672 patients (15.0%) were antibody positive. Four weeks later, 62/86 (72.1%) of initially antibody-positive patients had become negative. Considering only IgG titres, serology remained positive after 4 weeks in 90% (54/60) of patients with symptomatic COVID-19 and in 52.5% (21/40) of asymptomatic patients. The probability of an adequate serologic response (defined as the development of anti-SARS-CoV-2 antibodies that persisted at 4 weeks) was higher in patients who had symptomatic COVID-19 than in asymptomatic SARS-CoV-2 infection {odds ratio [OR) 4.04 [95% confidence interval (CI) 2.04-7.99]} corrected for age, Charlson comorbidity index score and time on HD. Living in a nursing home [OR 5.9 (95% CI 2.3-15.1)] was the main risk factor for SARS-CoV-2 infection. CONCLUSIONS: The anti-SARS-CoV-2 antibody immune response in HD patients depends on clinical presentation. The antibody titres decay earlier than previously reported for the general population. This inadequate immune response raises questions about the efficacy of future vaccines.

Familial hypercholesterolemia in Gran Canaria: Founder mutation effect and high frequency of diabetes. / Hipercolesterolemia familiar en Gran Canaria: mutación con efecto fundador y alta frecuencia de diabetes.

INTRODUCTION: Gran Canaria is a region of genetic isolation of familial hypercholesterolemia due to a founder mutation, p. [Tyr400_Phe402del], in the LDL receptor (LDLR) gene. Initial data suggest that its carriers could have a high prevalence of diabetes. MATERIAL AND METHODS: Patients over 30 years of age with familial hypercholesterolemia and a confirmed mutation in LDLR were recruited from a tertiary hospital in Gran Canaria. The prevalence of diabetes and other clinical data were compared among carriers of p. [Tyr400_Phe402del] and those with other LDLR mutations. RESULTS: 76.4% of the 89 participants were carriers of p.[Tyr400_Phe402del]. The prevalence of diabetes in this group was significantly higher (25 vs. 4%, P=.045). These cases also had a higher prevalence of cardiovascular disease and higher levels of LDL cholesterol and triglycerides. There were no differences in age, weight, body mass index, waist, age of onset, and time of statin treatment. However, they required PCSK9 inhibitors more often (51.5 vs 24%, P=.027). CONCLUSIONS: The mutation p.[Tyr400_Phe402del] is associated with a high prevalence of diabetes, not explained by classic risk factors, such as age, obesity, or long-term use of statins.

Maternally inherited hypercholesterolemia does not modify the cardiovascular phenotype in familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by a high risk of cardiovascular disease when not in lipid-lowering treatment. However, there is a large variability in the clinical presentation in heterozygous subjects (HeFH). Maternal hypercholesterolemia has been proposed as a cardiometabolic risk factor later in life. Whether this phenotype variability depends on the mother or father origin of hypercholesterolemia is unknown. The objective of this study was to analyze potential differences in anthropometry, superficial lipid deposits, comorbidities, and lipid concentrations depending on the parental origin of hypercholesterolemia within a large group of HeFH. METHODS: This is a cross-sectional observational, multicenter, nation-wide study in Spain. We recruited adults with HeFH to study clinical differences according to the parental origin. Data on HeFH patients were obtained from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. RESULTS: HeFH patients were grouped in 1231 HeFH-mother-offspring aged 45.7 (16.3) years and 1174 HeFH-father-offspring aged 44.8 (16.7) years. We did not find any difference in lipid parameters (total cholesterol, triglycerides, LDLc, HDLc, and Lp(a)), nor in the comorbidities studied (cardiovascular disease prevalence, age of onset of cardiovascular disease, obesity, diabetes, and hypertension) between groups. Lipid-lowering treatment did not differ between groups. The prevalence of comorbidities did not show differences when they were studied by age groups. CONCLUSIONS: Our research with a large group of subjects with HeFH shows that a potential maternal effect is not relevant in FH. However, due to the size of our sample, potential differences between genders cannot be completely ruled out. This implies that severe maternal hypercholesterolemia during pregnancy is not associated with additional risk in the FH affected offspring.