HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

Differential prognosis of patients that are candidates for standard, short or prolonged dual antiplatelet treatment discharged after an acute coronary syndrome.

BACKGROUND: Current evidence supports the efficacy of prolonged dual antiplatelet treatment (DAPT) for patients at high-ischemic risk and low bleeding risk as well as the efficacy and safety of short DAPT in high-bleeding risk (HBR) patients. METHODS: We evaluated patterns of DAPT candidates in all patients discharged in 2 hospitals after an acute coronary syndrome (ACS). Patients categorized in 3 groups: 1) short-DAPT candidates if they met 1 major o 2 minor criteria for HBR, by the 2019 ARC-HBR criteria; 2) prolonged-DAPT candidates if were not HBR and had recurrent ACS, complex percutaneous coronary interventions or diabetes; 3) standard 12 months DAPT if were not include in the previous 2 groups. Major bleeding (MB) was registered according to 3 or 5 of the BARC consortium definitions. RESULTS: We included 8252 patients and 3215 (39 %) were candidates for abbreviated DAPT, 3119 (37.8 %) for prolonged DAPT, and 1918 (23.2 %) for 12 m DAPT. Relevant differences were observed between the 3 categories beyond the bleeding risk. Median follow-up was 57 months. Multivariate analysis identified higher risk of all-cause mortality (HR: 1.96 95 % CI 1.45-2.67; p < 0.001), cardiovascular mortality (HR: 2.10 95 % CI 1.39-3.19; p < 0.011), MACE (HR: 1.69 95 % 1.50-2.02; p < 0.001) and MB (sHR: 3.41 95 % CI 1.45-8.02; p = 0.005) in candidates to short DAPT. Candidates to prolonged DAPT had higher risk of MACE (HR: 1.17 95 % CI 1.02-1.35; p = 0.027). CONCLUSIONS: Almost two thirds of patients discharged after an ACS would be candidates for short or prolonged DAPT and these patients are at higher risk of MACE and mortality.

Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome.

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.

Increased Risk of Heart Failure in Elderly Patients Treated with Beta-Blockers After AV Node Ablation.

INTRODUCTION: Controversy exists regarding the indication of beta-blockers (BB) in different scenarios in patients with cardiovascular disease. We sought to evaluate the effect of BB on survival and heart failure (HF) hospitalizations in a sample of pacemaker-dependent patients after AV node ablation to control ventricular rate for atrial tachyarrhythmias. METHODS: A retrospective study including consecutive patients that underwent AV node ablation was conducted in a single center between 2011 and 2019. The study's primary endpoints were the incidence of all-cause mortality, first HF hospitalization and the cumulative incidence of subsequent hospitalizations for HF. Competing risk analyses were employed. RESULTS: A total of 111 patients with a mean age of 73.9 years were included in the study. After a median follow-up of 45.5 months, 43 patients had died (38.7%) and 31 had been hospitalized for HF (27.9%). The recurrent HF hospitalization rate was 74/1000 patients/year. Patients treated with BB had a non-significant trend to higher mortality rates and a higher risk of recurrent HF hospitalizations (incidence rate ratio 2.23, 95% confidence interval 1.12-4.44; p = 0.023). CONCLUSION: After an AV node ablation, the use of BB is associated with an increased risk of HF hospitalizations in a cohort of elderly patients.

Remnant cholesterol in patients admitted for acute coronary syndromes.

BACKGROUND: Remnant cholesterol has been identified as one of leading lipid values associated with the incidence of coronary heart disease. There is scarce evidence on its distribution and prognostic value in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: We included all consecutive patients admitted for ACS in two different centres. Remnant cholesterol was calculated by the equation: total cholesterol minus LDL cholesterol minus HDL cholesterol, and values ≥30 were considered high. Among the 7479 patients, median remnant cholesterol level was 28 mg/dL (21-39), and 3429 (45.85%) patients had levels ≥30 mg/dL. Age (r: -0.29) and body mass index (r: 0.44) were the variables more strongly correlated. At any given age, patients with overweigh or obesity had higher levels. In-hospital mortality was 3.75% (280 patients). Remnant cholesterol was not associated to higher in-hospital mortality risk (odds ratio: 0.89; P = 0.21). After discharge (median follow-up of 57 months), an independent and linear risk of all-cause mortality and heart failure (HF) associated to cholesterol remnant levels was observed. Remnant cholesterol levels >60 mg/dL were associated to higher risk of mortality [hazard ratio (HR): 1.49 95% CI 1.08-2.06; P = 0.016], cardiovascular mortality (HR: 1.49 95% CI 1.08-2.06; P = 0.016), and HF re-admission (sub-HR: 1.55 95% CI 1.14-2.11; P = 0.005). CONCLUSIONS: Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is inversely correlated with age and positively with body mass index. Remnant cholesterol levels were not associated to higher in-hospital mortality risk, but they were associated with higher long-term risk of mortality and HF.

Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is related to body mass index and negatively with age. Remnant cholesterol it is not associated to higher in-hospital mortality risk, but it confers higher long-term risk of mortality and heart failure.

Should PRECISE-DAPT be included for long-term prognostic stratification of diabetic patients with NSTEACS?

AIMS: There are insufficient data regarding risk scores validation in patients with diabetes mellitus and non-ST elevation acute coronary syndrome (NSTEACS). We performed a diabetes mellitus-specific analysis of cardiovascular outcomes after NSTEACS. We tested the predictive power of the Global Registry of Acute Coronary Events (GRACE) and PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti-Platelet Therapy (PRECISE-DAPT) scores. METHODS: This work is a retrospective analysis that included 7,415 consecutive NSTEACS patients from two Spanish Universitarian hospitals between the years 2003 and 2017. The area under the ROC curve among with and without diabetes mellitus patients was calculated, to evaluate the predictive power of both scores.  RESULTS: Among the study participants, 2124 patients (28.0%) were diabetic. The median follow-up was 54,3 months (IQR 24,7-80,0 months). Diabetic patients were more women (30.5% vs. 25.7%) and older (70.0 ± 10.8 vs. 65.3 ± 13.2 years old); they had higher GRACE (146 ± 36 vs. 137 ± 36), PRECISE-DAPT (15 ± 7 vs. 18 ± 9) at admission. Early invasive coronary angiography (≤ 24 h after admission) was performed more frequently in non-diabetic. We tested the predictive power of the GRACE and PRECISE-DAPT risk scores among diabetic and non-diabetic. PRECISE-DAPT risk score showed a good predictive power for all-cause mortality, cardiovascular mortality and MACE in diabetic admitted with NSTEACS, without differences compared to non-diabetic. CONCLUSIONS: PRECISE-DAPT risk score has an appropriate predictive power in diabetic patients admitted with NSTEACS compared to non-diabetic NSTEACS. However, GRACE would be predictive worse in diabetic during long-term follow-up in a large contemporary registry.

Early angiography in elderly patients with non-ST-segment elevation acute coronary syndrome: The cardio CHUS-HUSJ registry.

BACKGROUND: In elderly patients with non-ST elevation acute coronary syndrome (NSTEACS), while routine invasive management is established in high-risk NSTEACS patients, there is still uncertainty regarding the optimal timing of the procedure. METHODS: This study analyzes the association of early coronary angiography with all-cause mortality, cardiovascular mortality, heart failure (HF) hospitalization, and major adverse cardiovascular events (MACE) in patients older than 75 years old with NSTEACS. This retrospective observational study included 7811 consecutive NSTEACS patients who were examined between the years 2003 and 2017 at two Spanish university hospitals. There were 2290 patients older than 75 years old. We compared their baseline characteristics according to the early invasive strategy used (coronarography ≤24 h vs. coronarography >24 h) after the diagnosis of NSTEACS. RESULTS: Among the study participants, 1566 patients (68.38%) underwent early invasive coronary intervention. The mean follow-up period was 46 months (interquartile range 18-71 months). This association was also maintained after propensity score matching: early invasive strategy was significantly related to lower all-cause mortality [HR 0.61 (95% CI 0.51-0.71)], cardiovascular mortality [HR 0.52 (95% CI 0.43-0.63)], and MACE [HR 0.62 (CI 95% 0.54-0.71)]. CONCUSIONS: In a contemporary real-world registry of elderly NSTEACS patients, early invasive management significantly reduced all-cause mortality, cardiovascular mortality, and MACE during long-term follow-up. BRIEF SUMMARY: In this real-world retrospective observational study that included 2451 patients older than 75 years old, 1566 patients (68.38%) underwent early invasive coronary intervention. After performing a propensity score matching, the early invasive strategy was still associated with lower all-cause mortality [HR (hazard ratio) 0.61, 95% CI (95% confidence interval) (0.51-0.71)], cardiovascular mortality [HR 0.52 (95%CI 0.43-0.63)], and MACE [HR 0.62 (95%CI 0.54-0.71)] during long-term follow-up.

Predictive Value of Pro-BNP for Heart Failure Readmission after an Acute Coronary Syndrome.

BACKGROUND: N-terminal pro-brain natural peptide (NT-pro-BNP) is a well-established biomarker of tissue congestion and has prognostic value in patients with heart failure (HF). Nonetheless, there is scarce evidence on its predictive capacity for HF re-admission after an acute coronary syndrome (ACS). We performed a prospective, single-center study in all patients discharged after an ACS. HF re-admission was analyzed by competing risk regression, taking all-cause mortality as a competing event. Results are presented as sub-hazard ratios (sHR). Recurrent hospitalizations were tested by negative binomial regression, and results are presented as incidence risk ratio (IRR). RESULTS: Of the 2133 included patients, 528 (24.8%) had HF during the ACS hospitalization, and their pro-BNP levels were higher (3220 pg/mL vs. 684.2 pg/mL; p < 0.001). In-hospital mortality was 2.9%, and pro-BNP was similarly higher in these patients. Increased pro-BNP levels were correlated to increased risk of HF or death during the hospitalization. Over follow-up (median 38 months) 243 (11.7%) patients had at least one hospital readmission for HF and 151 (7.1%) had more than one. Complete revascularization had a preventive effect on HF readmission, whereas several other variables were associated with higher risk. Pro-BNP was independently associated with HF admission (sHR: 1.47) and readmission (IRR: 1.45) at any age. Significant interactions were found for the predictive value of pro-BNP in women, diabetes, renal dysfunction, STEMI and patients without troponin elevation. CONCLUSIONS: In-hospital determination of pro-BNP is an independent predictor of HF readmission after an ACS.

Prognostic benefit from an early invasive strategy in patients with non-ST elevation acute coronary syndrome (NSTEACS): evaluation of the new risk stratification in the NSTEACS European guidelines.

OBJECTIVES: The objective of our work is to evaluate the prognostic benefit of an early invasive strategy in patients with high-risk NSTACS according to the recommendations of the 2020 clinical practice guidelines during long-term follow-up. METHODS: This retrospective observational study included 6454 consecutive NSTEACS patients. We analyze the effects of early coronary angiography (< 24 h) in patients with: (a) GRACE risk score > 140 and (b) patients with "established NSTEMI" (non ST-segment elevation myocardial infarction defined by an increase in troponins) or dynamic ST-T-segment changes with a GRACE risk score < 140. RESULTS: From 2003 to 2017, 6454 patients with "new high-risk NSTEACS" were admitted, and 6031 (93.45%) of these underwent coronary angiography. After inverse probability of treatment weighting, the long-term cumulative probability of being free of all-cause mortality, cardiovascular mortality and MACE differed significantly due to an early coronary intervention in patients with NSTEACS and GRACE > 140 [HR 0.62 (IC 95% 0.57-0.67), HR 0.62 (IC 95% 0.56-0.68), HR 0.57 (IC 95% 0.53-0.61), respectively]. In patients with NSTEACS and GRACE < 140 with established NSTEMI or ST/T-segment changes, the benefit of the early invasive strategy is only observed in the reduction of MACE [HR 0.62 (IC 95% 0.56-0.68)], but not for total mortality [HR 0.96 (IC 95% 0.78-1.2)] and cardiovascular mortality [HR 0.96 (IC 95% 0.75-1.24)]. CONCLUSIONS: An early invasive management is associated with reduced all-cause mortality, cardiovascular mortality and MACE in NSTEACS with high GRACE risk score. However, this benefit is less evident in the subgroup of patients with a GRACE score < 140 with established NSTEMI or ST/T-segment changes.

Direct Oral Anticoagulants Versus Vitamin-K Antagonist After PCIs in Patients With AF: A Meta-analysis of Cardiac Ischemic Events.

BACKGROUND: Clinical trials have assessed the effect of direct oral antagonists (DOACs) in patients with atrial fibrillation (AF) after percutaneous coronary interventions (PCI). Studies were designed to test the effect on bleeding incidence, but concerns related to safety on ischemic events remain. METHODS: We performed a meta-analysis with currently available studies involving DOACs versus Vitamin-K antagonist (VKA) in patients with AF after PCI. The primary endpoint was the incidence of cardiac ischemic events, including myocardial infarction and stent thrombosis. Secondary endpoints were the incidence of stroke, all-cause mortality, and major bleeding. RESULTS: Eleven thousand twenty-three patients were included in the analysis: 5510 receiving DOACs and 5513 VKA. A total of 190 cases of myocardial infarction were registered in patients treated with DOACs and 177 in patients on VKA, and no statistical difference was noted [relative risk (RR): 1.07 95% confidence interval (CI) 0.88-1.31]. The incidence of stent thrombosis was very low with no differences between both treatment strategies (RR: 1.14 95% CI 0.76-1.71). The incidence of cardiac ischemic events was the same in patients receiving DOACs or VKA (HR 1.09 95% CI 0.91-1.30). No differences were observed in the incidence of stroke (RR: 0.86 95% CI 0.61-1.23) or mortality (RR: 1.09, 95% CI 0.90-1.31). Treatment with DOACs was associated with 34% reduction in major bleeding (RR: 0.66, 95% CI 0.54-0.81). CONCLUSIONS: Treatment with DOACs in patients with AF after a PCI do not increase the risk of cardiac ischemic events, stroke, or death and reduce the incidence of major bleeding by 34% as compared with VKA.

New-onset heart failure after acute coronary syndrome in patients without heart failure or left ventricular dysfunction.

INTRODUCTION AND OBJECTIVES: Coronary heart disease is the leading cause of heart failure (HF). The aim of this study was to assess the risk of readmission for HF in patients with acute coronary syndrome without previous HF or left ventricular dysfunction. METHODS: Prospective study of consecutive patients admitted for acute coronary syndrome in 2 institutions. Risk factors for HF were analyzed by competing risk regression, taking all-cause mortality as a competing event. RESULTS: We included 5962 patients and 567 (9.5%) experienced at least 1 hospital readmission for acute HF. Median follow-up was 63 months and median time to HF readmission was 27.1 months. The cumulative incidence of HF was higher than mortality in the first 7 years after hospital discharge. A higher risk of HF readmission was associated with age, diabetes, previous coronary heart disease, GRACE score> 140, peripheral arterial disease, renal dysfunction, hypertension and atrial fibrillation; a lower risk was associated with optimal medical treatment. The incidence of HF in the first year of follow-up was 2.73% and no protective variables were found. A simple HF risk score predicted HF readmissions risk. CONCLUSIONS: One out of 10 patients discharged after an acute coronary syndrome without previous HF or left ventricular dysfunction had new-onset HF and the risk was higher than the risk of mortality. A simple clinical score can estimate individual risk of HF readmission even in patients without previous HF or left ventricular dysfunction.

Estimation of the major cardiovascular events prevention with Inclisiran.

BACKGROUND AND AIMS: The ORION 10-11 trials have reported the efficacy of Inclisiran on low-density lipoprotein cholesterol (LDLc) reduction, and also suggested prevention of major cardiovascular events (MACE) incidence. METHODS: We have performed a meta-analysis of the available studies, involving PCSK9 inhibitors or Inclisiran for >6 months, that reported the incidence of MACE. The primary endpoint was MACE incidence, as reported in outcomes-based randomized clinical trials (OB-RCT) and non OB-RCT. Analyses were performed using fixed effect models and fractional polynomial regression. RESULTS: The meta-analysis included a total of 57,431 patients, 1592 treated with Inclisiran and 28,259 with PSCK9 inhibitors (17,244 with evolocumab and 11,015 with alirocumab). Baseline mean LDLc was 104.1 (12.9) mg globally. On-treatment mean LDLc was 40.1 (7.8) mg/dl and mean absolute LDLc reduction was 60.6 (10.3) mg/dl. A total of 5389 MACE were reported, 2482 in patients receiving the study drug and 2907 in patients assigned to placebo. Treatment was associated with OB-RCT and no heterogeneity was observed. The estimation of MACE reduction associated with LDLc reduction, adjusted by age, diabetes, hypertension and baseline LDLc, provided a linear trend in the risk of MACE and LDLc reduction that was linear and all studies fitted properly. CONCLUSIONS: The results of the ORION 10-11 trials are in concordance with results of trials involving treatment with PCSK9 inhibitors. The results of the ORION-4 trial will provide definite evidence on the effects of Inclisiran on MACE reduction.

Understanding Erectile Dysfunction in Hypertensive Patients: The Need for Good Patient Management.

Erectile dysfunction (ED) is defined as a man's consistent or recurrent inability to attain and/or maintain penile erection enough for successful vaginal intercourse. ED affects a large part of the population, increasing its incidence with age and comorbidities. It is estimated by the year 2025, 322 million men will suffer from ED. Incidence of ED has been related not only to chronic diseases such as diabetes mellitus, metabolic syndrome, hyperlipidemia, psychiatric diseases or urinary tract diseases, but also to hypertension and especially to antihypertensive treatments. This review summarizes current knowledge about the management of ED in hypertensive men and its role as cardiovascular disease predictor.

A simple score to select patients for manual thrombectomy in emergent percutaneous coronary interventions: the DDTA score.

BACKGROUND: The objective of manual thrombectomy is the removal of occlusive thrombus to improve the results of primary angioplasty. The better understanding of the factors associated with successful manual thrombectomy may provide relevant information regarding thrombus formation and resolution. METHODS: Observational study of all consecutive patients remitted for emergent percutaneous coronary intervention (PCI) in a single centre. Successful manual thrombectomy was considered when TIMI 3 was achieved after using the device and a score to predict successful manual thrombectomy was designed. RESULTS: We included 618 patients, 65.1% treated with manual thrombectomy. No relevant differences in clinical features or time delays were observed between patients treated with vs. without manual thrombectomy, but manual thrombectomy treated patients received more often dual antiplatelet treatment (DAPT) before PCI. Final TIMI flow 3 was achieved in most patients and more frequently in manual thrombectomy treated patients (94.8 vs. 86.6%; P < 0.01). The successful manual thrombectomy rate was 81.3% and it was higher in patients pretreated with DAPT (89.0 vs. 73.3%; P < 0.01). The time delay to first medical contact was not related to the final TIMI 3, but it was significantly and negatively related to successful manual thrombectomy. According to the multivariate analysis, we designed the DDTA score: DAPT pretreatment (2), delay less than 2 h (3) or 2-4 h (2), TIMI flow improvement after wiring the lesion (2) and age less than 55 years (3). Patients with DDTA score at least 4 had lower no-reflow, mortality and major cardiovascular complications incidence. CONCLUSION: The DDTA score (DAPT pretreatment, time delays, TIMI flow improvement after wiring the lesion and age) identifies patients who benefit mostly from manual thrombectomy.