The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.

Aims: The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD). Methods and results: Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; P < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; P = 0.042), equipotent drugs (HR = 1.14; P = 0.031), and other therapies cohorts (HR = 1.17; P = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented. Conclusion: In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

Design and validation of a new questionnaire with a gender perspective to measure medication adherence for secondary prevention of ischaemic heart disease: study protocol.

INTRODUCTION AND OBJECTIVES: Only about 50% of chronic patients in high-income countries adhere to their treatment. There are methods to measure medication adherence but none of them can be considered optimal. This study will aim to design and validate a questionnaire to measure medication adherence in patients with ischaemic heart disease using a direct method as a gold-standard adherence measure and taking into account the gender perspective. Moreover, the profile of low adherence in these patients will be determined. METHODS AND ANALYSIS: First study phase consists on the questionnaire design following the next steps: identification of the dimensions, definition of the target population, questionnaire items and order, response coding, questionnaire instructions, content validity by experts and understandability. In the second phase, a cross-sectional study will be performed to end the questionnaire development and validate it. Four hundred and forty patients (50% female) with acute coronary syndrome receiving treatment within the previous 12 months will be included. Patient will answer the initial questionnaire and adherence to aspirin and statin will be measured using a direct method (drug concentration analysis in blood) and other questionnaires. From the set of preselected questionnaire items, those most closely associated with the gold standard measure will be selected using multivariate statistics. ETHICS AND DISSEMINATION: All participants gave their written informed consent before participating in the study. The study protocol follows the recommendations of the Declaration of Helsinki and was approved by the ethics committees of the three participating centres. The results of this study will be displayed at national and international conferences and in peer-reviewed scientific journals.

Validez en la predicción de riesgo de la escala SCORE en una población mediterránea con hipertensión arterial / Predictive validity of the risk SCORE model in a Mediterranean population with arterial hypertension

Introducción y objetivos: La hipertensión arterial es el factor de riesgo más prevalente a nivel global. Se recomienda el cálculo del riesgo cardiovascular en pacientes hipertensos antes del inicio del tratamiento. Este estudio tuvo como objetivo evaluar el valor predictivo y la utilidad clínica de la escala SCORE para prevenir eventos cardiovasculares y mortalidad por todas las causas en los pacientes con hipertensión arterial. Métodos: Se incluyeron los pacientes con hipertensión arterial de la cohorte ESCARVAL-RISK. El riesgo cardiovascular se calculó mediante la escala SCORE. Todas las muertes y eventos cardiovasculares se registraron durante un periodo de 5 años de seguimiento. Se calculó la sensibilidad, la especificidad y los valores predictivos para diferentes puntos de corte, y se evaluó el efecto de diferentes factores de riesgo sobre la exactitud diagnóstica de las gráficas SCORE. Resultados: En una cohorte final de 9.834 pacientes, hubo 555 eventos cardiovasculares y 69 muertes. El valor de riesgo recomendado para iniciar tratamiento farmacológico (5%) presentó una especificidad del 92% para la muerte y del 91% para los eventos cardiovasculares, y una sensibilidad del 20% para la muerte y del 22% para los eventos cardiovasculares. Además, la escala clasificó al 80,4% de los pacientes que sufrieron un evento cardiovascular, y al 78,3% de los que murieron, como de bajo riesgo. La edad, el índice de masa corporal, la retinopatía y el tratamiento anticoagulante se asociaron con una reducción en la capacidad predictiva de la escala SCORE, mientras que ser mujer se asoció con mejor predicción de riesgo. Conclusiones: La capacidad predictiva de la escala SCORE para la enfermedad cardiovascular y la mortalidad total en los pacientes con hipertensión arterial es limitada.(AU)

Introduction and objectives: Hypertension is the most prevalent risk factor globally. Calculation of cardiovascular risk in hypertensive patients before initiation of treatment is recommended. This study aimed to assess the predictive value and clinical utility of the SCORE scale in preventing cardiovascular events and all-cause mortality in patients with hypertension. Methods: Patients with hypertension from the ESCARVAL-RISK cohort were included. Cardiovascular risk was calculated using the SCORE scale. All deaths and cardiovascular events were recorded during a 5-year follow-up period. Sensitivity, specificity and predictive values were calculated for different cut-off points and the effect of different risk factors on the diagnostic accuracy of SCORE charts were assessed. Results: In a final cohort of 9834 patients, there were 555 cardiovascular events and 69 deaths. The recommended risk value for initiating drug treatment (5%) had a specificity of 92% for death and 91% for cardiovascular events, and a sensitivity of 20% for death and 22% for cardiovascular events. In addition, the scale classified 80.4% of patients who experienced a cardiovascular event and 78.3% of those who died as low risk. Age, body mass index, retinopathy and anticoagulant therapy were associated with reduced predictive ability of the SCORE scale, while being female was associated with better risk prediction. Conclusions: The predictive ability of the SCORE scale for cardiovascular disease and total mortality in patients with hypertension is limited.(AU)

[Predictive validity of the risk SCORE model in a Mediterranean population with arterial hypertension]. / Validez en la predicción de riesgo de la escala SCORE en una población mediterránea con hipertensión arterial.

INTRODUCTION AND OBJECTIVES: Hypertension is the most prevalent risk factor globally. Calculation of cardiovascular risk in hypertensive patients before initiation of treatment is recommended. This study aimed to assess the predictive value and clinical utility of the SCORE scale in preventing cardiovascular events and all-cause mortality in patients with hypertension. METHODS: Patients with hypertension from the ESCARVAL-RISK cohort were included. Cardiovascular risk was calculated using the SCORE scale. All deaths and cardiovascular events were recorded during a 5-year follow-up period. Sensitivity, specificity and predictive values were calculated for different cut-off points and the effect of different risk factors on the diagnostic accuracy of SCORE charts were assessed. RESULTS: In a final cohort of 9834 patients, there were 555 cardiovascular events and 69 deaths. The recommended risk value for initiating drug treatment (5%) had a specificity of 92% for death and 91% for cardiovascular events, and a sensitivity of 20% for death and 22% for cardiovascular events. In addition, the scale classified 80.4% of patients who experienced a cardiovascular event and 78.3% of those who died as low risk. Age, body mass index, retinopathy and anticoagulant therapy were associated with reduced predictive ability of the SCORE scale, while being female was associated with better risk prediction. CONCLUSIONS: The predictive ability of the SCORE scale for cardiovascular disease and total mortality in patients with hypertension is limited.

Index and Repeat Ablation for Atrial Fibrillation in Older versus Younger Patients: A Propensity-Score Matching Analysis.

Catheter ablation is a well-established rhythm control therapy in atrial fibrillation (AF). Although the prevalence of AF increases dramatically with age, the prognosis and safety profile of index and repeat ablation procedures remain unclear in the older population. The primary endpoint of this study was to assess the arrhythmia recurrence, reablation and complication rates in older patients. Secondary endpoints were the identification of independent predictors of arrhythmia recurrence and reablation, including information on pulmonary vein (PV) reconnection and other atrial foci. Older (n=129, ≥70 years) and younger (n=129, <70 years) patients were compared using a propensity-score matching analysis based on age, gender, obesity, hypertension, dyslipidemia, diabetes mellitus, dilated left atrium, severe obstructive sleep apnea, cardiac disease, left systolic ventricular function, AF pattern and ablation technique. Arrhythmia recurrence and reablation were evaluated in both groups using a Cox regression analysis in order to identify predictors. During a 30-month follow-up period, there were no significant differences between older and younger patients in the arrhythmia-free survival (65.1% and 59.7%; log-rank test p=0.403) and complication (10.1% and 10.9%; p>0.999) rates after the index ablation. However, the reablation rate was significantly different (46.7% and 69.2%; p<0.05, respectively). In those patients who underwent reablation procedure (redo subgroups), there were no differences in the incidence of PV reconnection (38.1% redo-older and 27.8% redo-younger patients; p=0.556). However, the redo-older patients had lower reconnected PVs per patient (p<0.01) and lower atrial foci (2.3 and 3.7; p<0.01) than the redo-younger patients. A further important finding was that age was not an independent predictor of arrhythmia recurrence or reablation. Our data reveal that the AF index ablation in older patients had a similar efficacy and safety profile to younger patients. Therefore, age alone must not be considered a prognostic factor for AF ablation but the presence of limiting factors such as frailty and multiple comorbidities.

Lipoprotein(a) and Long-Term Recurrent Infarction After an Acute Myocardial Infarction.

Lipoprotein(a) (Lp[a]) is an emerging risk factor for incident ischemic heart disease. However, its role in risk stratification in in-hospital survivors to an index acute myocardial infarction (AMI) is scarcer, especially for predicting the risk of long-term recurrent AMI. We aimed to assess the relation between Lp(a) and very long-term recurrent AMI after an index episode of AMI. It is a retrospective analysis that included 1,223 consecutive patients with an AMI discharged from October 2000 to June 2003 in a single-teaching center. Lp(a) was assessed during index admission in all cases. The relation between Lp(a) at discharge and total recurrent AMI was evaluated through negative binomial regression. The mean age of the patients was 67.0 ± 12.3 years, 379 (31.0%) were women, and 394 (32.2%) were diabetic. The index event was more frequently non-ST-segment elevation myocardial infarction (66.0%). The median Lp(a) was 28.8 (11.8 to 63.4) mg/100 ml. During a median follow-up of 9.9 (4.6 to 15.5) years, 813 (66.6%) deaths and 1,205 AMI in 532 patients (43.5%) occurred. Lp(a) values were not associated with an increased risk of long-term all-cause mortality (p = 0.934). However, they were positively and nonlinearly associated with an increased risk of total long-term reinfarction (p = 0.016). In the subgroup analysis, there was no evidence of a differential effect for the most prevalent subgroups. In conclusion, after an AMI, elevated Lp(a) values assessed during hospitalization were associated with an increased risk of recurrent reinfarction in the very long term. Further prospective studies are warranted to evaluate their clinical implications.

Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study.

BACKGROUND AND AIMS: Cardiovascular risk increases during menopause, so the medical and scientific community should consider women's specific risk factors to prevent cardiovascular disease. This study aims to assess the risk factors for the incidence of major adverse cardiovascular events (MACE) exclusive to postmenopausal women. METHODS: We conducted a prospective cohort study in postmenopausal women aged 40 years and older, who were included in the UK Biobank cohort between 2006 and 2010 and followed to 2021 (12 years). A total of 156,787 women were followed for a median of 12.5 years (nearly 2 million person-years), and MACE risk was assessed using Fine-Gray competing risk models. RESULTS: The cumulative incidence of cardiovascular morbidity and mortality was 1.2% (0.97 cases per 1000 women-years). Not having taken birth control pills, not having children, and early menarche (≤12 years) were independently associated with cardiovascular morbidity and mortality. CONCLUSIONS: Risk factors for cardiovascular disease that are specific to women include early menarche, not having taken oral contraceptives, and reproductive history, and this relationship is independent of classic cardiovascular risk factors.

The efficacy of intensive lipid-lowering therapies on the reduction of LDLc and of major cardiovascular events.

BACKGROUND: Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control. METHODS: We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality. RESULTS: Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality. CONCLUSIONS: Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction.

Clinical Benefit of Bempedoic Acid in Randomized Clinical Trials.

Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome of the metanalysis was the incidence of major adverse cardiovascular events, defined by each study protocol. Secondary outcomes for the analyses were myocardial infarction, stroke, myocardial revascularization, cardiovascular death, and all-cause death. Results of 4 clinical trials evaluated contained a total of 17,324 patients; 9,236 received bempedoic acid for a median of 46.6 months. The mean baseline LDLc was 129.4 (22.8) mg/100 ml and treatment was associated with a mean LDLc reduction of 26.0 (12.6) mg/100 ml. Treatment with bempedoic acid significantly reduced the incidence of major adverse cardiovascular events (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81 to 0.96), myocardial infarction (HR 0.76, 95% CI 0.66 to 0.89) and myocardial revascularization (HR 0.82, 95% CI 0.73 to 0.92); the crude incidence of stroke, cardiovascular or all-cause mortality were lower in patients in the bempedoic acid groups although no significant risk reduction was observed. No heterogeneity was observed in any of the end points. In conclusion, the metanalysis of the 4 clinical trials currently available with bempedoic acid provides reliable evidence of its clinical benefit with no signs of heterogeneity or harm.

Changes in circulating ApoJ-Glyc levels in patients with suspected acute coronary syndrome: The EDICA trial.

BACKGROUND: Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. OBJECTIVE: This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). METHODS: In suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). RESULTS: 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46-90] vs. 73 [56-95] µg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. CONCLUSIONS: Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.

Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World-MEMOGAL Study.

INTRODUCTION: The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. METHODS: This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (- 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints-the visuospatial/executive domain + 0.04 (p = 0.651), naming domain - 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain - 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain - 0.05 (p = 0.224)-but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level-0-54 mg/dL, 55-69 mg/dL and ≥ 70 mg/dL; p = 0.454-or between alirocumab and evolocumab arms. CONCLUSION: We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. REGISTRATION: ClinicalTtrials.gov Identifier number NCT04319081.

Effect of dapagliflozin on COVID-19 infection and risk of hospitalization.

BACKGROUND: Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection. METHODS: We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model. RESULTS: We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015). CONCLUSIONS: Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.

Valor pronóstico de la fibrosis hepática valorada por el índice FIB4 en pacientes ingresados por síndrome coronario agudo / Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome

Introducción y objetivos: La fibrosis hepática precede a la cirrosis y a la insuficiencia hepática. Las formas subclínicas de fibrosis hepática podrían aumentar el riesgo de eventos cardiovasculares. El objetivo fue describir el valor pronóstico del índice FIB-4 en pacientes con síndrome coronario agudo (SCA) sobre la mortalidad hospitalaria y el pronóstico posterior. Métodos: Estudio retrospectivo de pacientes con SCA en un centro. Los objetivos de análisis fueron la mortalidad en la fase hospitalaria y tras el alta, así como la insuficiencia cardiaca y el sangrado mayor (SM), que se evaluaron tomando como evento competitivo la mortalidad por todas las causas y se presentan los sub-hazard ratios (sHR). Los eventos recurrentes se evaluaron mediante la razón de tasas de incidencia (IRR). Resultados: Se incluyeron a 3.106 pacientes y el 6,66% tenía un índice FIB-4 ≥ 1,3. El análisis multivariado verificó mayor riesgo de mortalidad intrahospitalaria asociado al índice FIB-4 (OR = 1,24; p=0,016) y los pacientes con valores> 2,67 presentaron el doble de riesgo (OR = 2,35; p=0,038). Tras el alta (mediana de seguimiento 1.112 días) el índice FIB-4 no tuvo valor pronóstico de mortalidad pero valores ≥ 1,3 se asociaron a mayor riesgo del primer reingreso (Shr = 1,61; p=0,04) o recurrente (IRR =1,70; p=0,001) de IC. El índice FIB-4 ≥ 1,30 se asoció con mayor riesgo de SM (sHR = 1,62; p=0,030). Conclusiones: La evaluación de la fibrosis hepática por el índice FIB-4 identifica a los pacientes con SCA con mayor riesgo de mortalidad intrahospitalaria pero también con mayor riesgo de IC y SM tras el alta.(AU)

Introduction and objectives: Liver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). Methods: Retrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). Results: We included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). Conclusions : The assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.(AU)

The benefits of measuring the size and number of lipoprotein particles for cardiovascular risk prediction: A systematic review and meta-analysis / Los beneficios de medir el tamaño y el número de partículas de lipoproteínas para la predicción del riesgo cardiovascular: una revisión sistemática y un metaanálisis

Objective: Cardiovascular risk (CVR) is conventionally calculated by measuring the total cholesterol content of high-density lipoproteins (HDL) and low-density lipoproteins (LDL). The purpose of this systematic review was to assess the CVR associated with LDL and HDL particle size and number as determined by nuclear magnetic resonance (NMR) spectroscopy. Material and methods: A literature search was performed using the electronic databases MEDLINE and Scopus. All cohort and case–control studies published before January 1, 2019 that met the following inclusion criteria were included: HDL-P, LDL-P, HDL-Z and/or LDL-Z measured by NMR spectroscopy; cardiovascular event as an outcome variable; risk of cardiovascular events expressed as odds ratios or hazard ratios; only adult patients. A meta-analysis was performed for each exposure variable (4 for LDL and 5 for HDL) and for each exposure measure (highest versus lowest quartile and 1-standard deviation increment). Results: This review included 24 studies. Number of LDL particles was directly associated with CVR: risk increased by 28% with each standard deviation increment. LDL particle size was inversely and significantly associated with CVR: each standard deviation increment corresponded to an 8% risk reduction. CVR increased by 12% with each standard deviation increase in number of small LDL particles. HD, particle number and size were inversely associated with CVR. Conclusion: Larger particle size provided greater protection, although this relationship was inconsistent between studies. Larger number of LDL particles and smaller LDL particle size are associated with increased CVR. Risk decreases with increasing number and size of HDL particles.(AU)

Objetivo: El riesgo cardiovascular (RCV) se calcula convencionalmente midiendo el contenido de colesterol total de las lipoproteínas de alta densidad (HDL) y las lipoproteínas de baja densidad (LDL). El propósito de esta revisión sistemática fue evaluar el RCV asociado con el tamaño y el número de partículas de LDL y HDL, según lo determinado por espectroscopia de resonancia magnética nuclear (RMN). Material y métodos: Se realizó una búsqueda bibliográfica utilizando las bases de datos electrónicas Medline y Scopus. Se incluyeron todos los estudios de cohortes y de casos y controles publicados antes del 1 de enero de 2019, que cumplieron con los siguientes criterios de inclusión: HDL-P, LDL-P, HDL-Z y/o LDL-Z medidos por espectroscopia de RMN; evento cardiovascular como variable de resultado; riesgo de eventos cardiovasculares expresado como cociente de posibilidades o cociente de riesgos instantáneos; solo pacientes adultos. Se realizó un metaanálisis para cada variable de exposición (cuatro para LDL y cinco para HDL) y para cada medida de exposición (cuartil más alto vs. más bajo e incremento de 1 desviación estándar [DE]). Resultados: Esta revisión incluyó 24 estudios. El número de partículas LDL se asoció directamente con el RCV: el riesgo aumentó 28% con cada incremento de la DE. El tamaño de las partículas de LDL se asoció inversa y significativamente con el RCV: cada incremento de la DE correspondió a una reducción del riesgo de 8%. El RCV aumentó 12% con cada aumento de la DE en el número de partículas pequeñas de LDL. HDL, número y tamaño de partículas se asociaron inversamente con CVR. Conclusión: El tamaño de partícula más grande proporcionó una mayor protección, aunque esta relación fue inconsistente entre los estudios. Un mayor número de partículas de LDL y un tamaño de partícula de LDL más pequeño se asocian con un aumento de la RCV. El riesgo disminuye con el aumento del número y tamaño de las partículas de HDL.(AU)

Economic Burden Associated with the Treatment with a Cardiovascular Polypill in Secondary Prevention in Spain: Cost-Effectiveness Results of the NEPTUNO Study.

Purpose: The aim of this study was to estimate health-care resources utilization, costs and cost-effectiveness associated with the treatment with CNIC-Polypill as secondary prevention of atherosclerotic cardiovascular disease (ASCVD) compared to other treatments, in clinical practice in Spain. Patients and Methods: An observational, retrospective study was performed using medical records (economic results [healthcare perspective], NEPTUNO-study; BIG-PAC-database) of patients who initiated secondary prevention between 2015 and 2018. Patients were followed up to 2 years (maximum). Four cohorts were balanced with a propensity-score-matching (PSM): 1) CNIC-Polypill (aspirin+atorvastatin+ramipril), 2) Monocomponents (same separate drugs), 3) Equipotent (equipotent drugs) and 4) Other therapies ([OT], other cardiovascular drugs). Incidence of cardiovascular events, health-care resources utilization and healthcare and non-healthcare costs (2020 Euros) were compared. Incremental cost-effectiveness ratios per cardiovascular event avoided were estimated. Results: After PSM, 1614 patients were recruited in each study cohort. The accumulated incidence of cardiovascular events during the 24-month follow-up was lower in the CNIC-Polypill cohort vs the other cohorts (19.8% vs Monocomponents: 23.3%, Equipotent: 25.5% and OT: 26.8%; p<0.01). During the follow-up period, the CNIC-Polypill cohort also reduced the health-care resources utilization per patient compared to the other cohorts, particularly primary care visits (16.6 vs Monocomponents: 18.7, Equipotent: 18.9 and OT: 21.0; p<0.001) and hospitalization days (2.3 vs Monocomponents: 3.4, Equipotent: 3.7 and OT: 4.0; p<0.001). The treatment cost in the CNIC-Polypill cohort was lower than that in the other cohorts (€4668 vs Monocomponents: €5587; Equipotent: €5682 and OT: €6016; p<0.001) (Difference: -€919, -€1014 and -€1348, respectively). Due to the reduction of cardiovascular events and costs, the CNIC-Polypill is a dominant alternative compared to the other treatments. Conclusion: CNIC-Polypill reduces recurrent major cardiovascular events and costs, being a cost-saving strategy as secondary prevention of ASCVD.