Traditional risk factors and premature acute coronary syndromes in South Eastern Europe: a multinational cohort study.

Background: The age-standardized death rates under 65 years from ischemic heart disease in South Eastern Europe are approximately twice as high than the Western Europe average, but the reasons are not completely recognized. The aim of the present study was to address this issue by collecting and analyzing data from a large, multinational cohort. Methods: We enrolled 70,953 Caucasian patients with first acute coronary syndrome, from 36 urban hospital in 7 South Eastern European countries and assessed their life expectancy free of acute coronary syndrome and mortality within 30 days after hospital admission from acute coronary syndrome as estimated in relation to dichotomous categories of traditional risk factors (current smoking, hypertension, diabetes and hypercholesterolemia) stratified according to sex. Findings: Compared with patients without any baseline traditional risk factors, the presence of all four risk factors was associated with a 5-year shorter life expectancy free of acute coronary syndrome (women: from 67.1 ± 12.0 to 61.9 ± 10.3 years; r = -0.089; p < 0.001 and men: from 62.8 ± 12.2 to 58.9 ± 9.9 years; r = -0.096; p < 0.001). Premature acute coronary syndrome (women <67 years and men <63 years) was remarkably related to current smoking and hypercholesterolemia among women (RRs: 3.96; 95% CI: 3.72-4.20 and 1.31; 95% CI: 1.25-1.38, respectively) and men (RRs: 2.82; 95% CI: 2.71-2.93 and 1.39; 95% CI: 1.34-1.45, respectively). Diabetes was most strongly associated with death from premature acute coronary syndrome either in women (RR: 1.52; 95% CI: 1.29-1.79) or men (RR: 1.63; 95% CI: 1.41-1.89). Interpretation: Public health policies in South Eastern Europe should place significant emphasis on the four traditional risk factors and the associated lifestyle behaviors to reduce the epidemic of premature ischemic heart disease. Funding: None.

Early insulin resistance in normoglycemic low-risk individuals is associated with subclinical atherosclerosis.

BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with a higher burden of subclinical atherosclerosis (SA). However, the association with SA of earlier insulin resistance markers is poorly understood. The study assessed the association between the homeostatic model assessment of insulin resistance index (HOMA-IR) and SA in addition to the effect of cardiovascular risk factors (CVRFs) in individuals with normal HbA1c. METHODS: A cohort of 3,741 middle-aged individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study with basal HbA1c < 6.0% (< 42 mmol/mol) and no known CV disease underwent extensive imaging (multiterritorial vascular ultrasound and coronary artery calcium score, CACS) to assess the presence, burden, and extent of SA. RESULTS: Individuals with higher HOMA-IR values had higher rates of CVRFs. HOMA-IR showed a direct association with the multiterritorial extent of SA and CACS (p < 0.001) and with global plaque volume measured by 3-dimensional vascular ultrasound (p < 0.001). After adjusting for key CVRFs and HbA1c, HOMA-IR values ≥ 3 were associated with both the multiterritorial extent of SA (odds ratio 1.41; 95%CI: 1.01 to 1.95, p = 0.041) and CACS > 0 (odds ratio 1.74; 95%CI: 1.20 to 2.54, p = 0.004), as compared with the HOMA-IR < 2 (the reference HOMA-IR category). In a stratified analysis, this association remained significant in individuals with a low-to-moderate SCORE2 risk estimate (75.6% of the cohort) but not in high-risk individuals. CONCLUSIONS: The use of HOMA-IR identified low-risk individuals with a higher burden of SA, after adjusting for the effects of key traditional CVRFs and HbA1c. HOMA-IR is a simple measure that could facilitate earlier implementation of primary CV prevention strategies in clinical practice.

Update of HDL in atherosclerotic cardiovascular disease / Nuevos conceptos de las HDL en la enfermedad cardiovascular aterosclerótica

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the “HDL quality over quantity” hypothesis. The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors. (AU)

Estudios epidemiológicos respaldan una asociación inversa entre los niveles de colesterol de lipoproteínas de alta densidad (c-HDL) y la enfermedad cardiovascular aterosclerótica (ECVA), identificando el c-HDL como un importante factor de riesgo cardiovascular y postulando diversas funciones vasculares y cardioprotectoras de las HDL más allá de su capacidad para promover el transporte reverso del colesterol. Sin embargo, el fracaso de varios ensayos clínicos dirigidos a aumentar el c-HDL en pacientes con enfermedad cardiovascular manifiesta, puso en duda el concepto que incrementar la carga de c-HDL fuera una estrategia eficaz para potenciar sus propiedades protectoras. Paralelamente, numerosos estudios han evidenciado que las HDL son partículas complejas y heterogéneas cuya composición es esencial para mantener sus funciones protectoras, lo que refuerza la hipótesis de que «la calidad de las HDL prima sobre la cantidad». En el siguiente manuscrito revisamos el estado del arte sobre los últimos avances en torno a las funciones de las HDL en la ECVA, nos adentramos en los avances recientes en la comprensión de la complejidad de la composición de las partículas de HDL, incluidas las proteínas, los lípidos y otros componentes transportados por las HDL, y revisamos los resultados clínicos tras la administración de inductores del c-HDL, especialmente los inhibidores de la proteína transportadora del colesterol esterificado (CETP). (AU)

Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens.

We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration.

Update of HDL in atherosclerotic cardiovascular disease.

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the "HDL quality over quantity" hypothesis. The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors.

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years.

BACKGROUND: Atherosclerosis is a systemic disease that frequently begins early in life. However, knowledge about the temporal disease dynamics (ie, progression or regression) of human subclinical atherosclerosis and their determinants is scarce. OBJECTIVES: This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals by using multiterritorial 3-dimensional vascular ultrasound (3DVUS) imaging. METHODS: A total of 3,471 participants from the PESA (Progression of Early Subclinical Atherosclerosis) cohort study (baseline age 40-55 years; 36% female) underwent 3 serial 3DVUS imaging assessments of peripheral arteries at 3-year intervals. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden). Multivariable logistic regression models for progression and regression were developed using stepwise forward variable selection. RESULTS: Baseline to 6-year subclinical atherosclerosis progression occurred in 32.7% of the cohort (17.5% presenting with incident disease and 15.2% progressing from prevalent disease at enrollment). Regression was observed in 8.0% of those patients with baseline disease. The effects of higher low-density lipoprotein cholesterol (LDL-C) and elevated systolic blood pressure (SBP) on 6-year subclinical atherosclerosis progression risk were more pronounced among participants in the youngest age stratum (Pinteraction = 0.04 and 0.02, respectively). CONCLUSIONS: Over 6 years, subclinical atherosclerosis progressed in one-third of middle-age asymptomatic subjects. Atherosclerosis regression is possible in early stages of the disease. The impact of LDL-C and SBP on subclinical atherosclerosis progression was more pronounced in younger participants, a finding suggesting that the prevention of atherosclerosis and its progression could be enhanced by tighter risk factor control at younger ages, with a likely long-term impact on reducing the risk of clinical events. (Progression of Early Subclinical Atherosclerosis [PESA; also PESA-CNIC-Santander]; NCT01410318).

Bleeding and Ischemic Risks of Ticagrelor Monotherapy After Coronary Interventions.

BACKGROUND: In TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), among high-risk patients undergoing percutaneous coronary intervention (PCI), ticagrelor monotherapy vs continuation of dual antiplatelet therapy (DAPT) with aspirin and ticagrelor after completing a 3-month course of DAPT was associated with reduced bleeding, without an increase in ischemic events. OBJECTIVES: This investigation sought to study the clinical benefit of ticagrelor monotherapy vs DAPT by simultaneously modeling its associated potential bleeding benefits and ischemic harms on an individual patient basis. METHODS: Multivariable Cox regression models for: 1) Bleeding Academic Research Consortium type 2, 3, or 5 (BARC-2/3/5); and 2) cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke (major adverse cardiac and cerebrovascular event [MACCE]) were developed using stepwise forward variable selection. The coefficients in the BARC-2/3/5 and MACCE models were used to calculate bleeding and ischemic risk scores, respectively, for each patient (excluding the coefficient for randomized treatment). RESULTS: In the total study group (N = 7,119), BARC-2/3/5 occurred in 391 (5.5%) patients, and MACCE occurred in 258 (3.6%). There was a consistent reduction in bleeding events associated with ticagrelor monotherapy compared with DAPT across both bleeding and ischemic risk strata (P interaction = 0.54 and 0.11, respectively). Importantly, this benefit associated with ticagrelor monotherapy was not offset by an increase in MACCE at any level of bleeding or ischemic risk. CONCLUSIONS: Three months after PCI, discontinuing aspirin and maintaining ticagrelor monotherapy reduces bleeding in both higher-bleeding risk and lower-bleeding risk patients compared with continued DAPT. This benefit does not appear to be offset by greater ischemic risk. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease.

Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS-COVID-19 (International Survey of Acute Coronavirus Syndromes-COVID-19) registry. Patients with a confirmed diagnosis of SARS-CoV-2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06-2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69-1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42-0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75-2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (Pinteraction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34-3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

Sex differences and disparities in cardiovascular outcomes of COVID-19.

AIMS: Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. METHODS AND RESULTS: This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04). CONCLUSIONS: Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles.

Obesity is associated with metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM), further increasing an already heightened cardiovascular risk. Here, amongst obese class III bariatric surgery patients, we have investigated the effect of T2DM in serum and in two, same patient, adipose tissue (AT) depots through proteomic profile expression analyses. Serum and AT samples from subcutaneous (SAT) and visceral (VAT) fat were collected during bariatric surgery. Bead-based targeted multiplex assay systems were used to simultaneously detect and quantify multiple targets in serum samples (targeted proteomics) and analyze changes in adipokine serum composition. AT samples were assessed through an untargeted proteomics approach. Through a systems biology analysis of the proteomic data, information on the affected biological pathways was acquired. In obese class III individuals, the presence of T2DM induced a significantly higher systemic release of ghrelin, GLP-1, glucagon, MMP3, BAFF, chitinase 3-like 1, TNF-R1 and TNF-R2, and a lower systemic release of IL-8. SAT and VAT proteomes belonging to the same patient showed significant differences in local protein content. While the proteins upregulated in VAT were indicative of metabolic dysregulation, SAT protein upregulation suggested adequate endocrine regulation. The presence of T2DM significantly affected VAT protein composition through the upregulation of dysregulating metabolic pathways, but SAT protein composition was not significantly modified. Our results show that T2DM induces metabolic dysregulation in obese individuals with changes in systemic marker levels and impairment of proteostasis in VAT but not in SAT.

Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone on cardiac fibroblasts of patients with heart failure and reduced ejection fraction.

AIMS: Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM-1 µM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound-healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers [fold-change (Log2): COL1A1-1.3; IL-1b-1.9; IL-6-1.7; FN1-2.9 (P < 0.05)]. Dapagliflozin slowed the migration rate of HFrEF fibroblasts in a dose-dependent manner and markedly decreased the expression of IL-1ß, IL-6, MMP3, MMP9, GAL3, and FN1. SGLT2i had no effect on control fibroblasts. These effects were associated with decreased phosphorylation of AKT/GSK3 and PYK2 kinases and the signal transducer and activator of transcription (STAT). A combination of dapagliflozin + LCZ696 further decreased fibroblast migration, although it did not have a significant effect on the regulation of signalling pathways and the expression of biomarkers induced by SGLT2 inhibition alone. In contrast, the combination of dapagliflozin + spironolactone did not change the migration rate of fibroblast but significantly altered SGLT2i responses on MMP9, GAL3, and IL-1b expression, in association with increased phosphorylation of the kinases AKT/GSK3 and ERK1/2. CONCLUSIONS: SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure.

A comprehensive and longitudinal cardiac magnetic resonance imaging study of the impact of coronary ischemia duration on myocardial damage in a highly translatable animal model.

OBJECTIVES: We performed a comprehensive assessment of the effect of myocardial ischemia duration on cardiac structural and functional parameters by serial cardiac magnetic resonance (CMR) and characterized the evolving scar. BACKGROUND: CMR follow-up on the cardiac impact of time of ischemia in a closed-chest animal model of myocardial infarction with human resemblance is missing. METHODS: Pigs underwent MI induction by occlusion of the left anterior descending (LAD) coronary artery for 30, 60, 90 or 120 min and then revascularized. Serial CMR was performed on day 3 and day 42 post-MI. CMR measurements were also run in a sham-operated group. Cellular and molecular changes were investigated. RESULTS: On day 3, cardiac damage and function were similar in sham and pigs subjected to 30 min of ischemia. Cardiac damage (oedema and necrosis) significantly increased from 60 min onwards. Microvascular obstruction was extensively seen in animals with ≥90 min of ischemia and correlated with cardiac damage. A drop in global systolic function and wall motion of the jeopardized segments was seen in pigs subjected to ≥60 min of ischemia. On day 42, scar size and cardiac dysfunction followed the same pattern in the animals subjected to ≥60 min of ischemia. Adverse left ventricular remodelling (worsening of both LV volumes) was only present in animals subjected to 120 min of ischemia. Cardiac fibrosis, myocyte hypertrophy and vessel rarefaction were similar in the infarcted myocardium of pigs subjected to ≥60 min of ischemia. No changes were observed in the remote myocardium. CONCLUSION: Sixty-minute LAD coronary occlusion already induces cardiac structural and functional alterations with longer ischemic time (120 min) causing adverse LV remodelling.

DJ-1 administration exerts cardioprotection in a mouse model of acute myocardial infarction.

Cardiovascular diseases, and particularly acute myocardial infarction (MI), are the most common causes of death worldwide. Infarct size is the major predictor of clinical outcomes in MI. The Parkinson's disease associated protein, DJ-1 (also known as PARK7), is a multifunctional protein with chaperone, redox sensing and mitochondrial homeostasis activities. Previously, we provided the evidence for a central role of endogenous DJ-1 in the cardioprotection of post-conditioning. In the present study, we tested the hypothesis that systemic administration of recombinant DJ-1 exerts cardioprotective effects in a mouse model of MI and also explored the associated transcriptional response. We report a significant treatment-induced reduction in infarct size, leukocyte infiltration, apoptosis and oxidative stress. Effects potentially mediated by G-protein-coupled receptor signaling and modulation of the immune response. Collectively, our results indicate a protective role for the exogenously administrated DJ-1 upon MI, and provide the first line of evidence for an extracellular activity of DJ-1 regulating cardiac injury in vivo.

Supplementation With Spirulina Reduces Infarct Size and Ameliorates Cardiac Function in a Pig Model of STEMI.

Background and Aims: Myocardial infarction (MI) is the clinical manifestation of atherosclerotic coronary artery disease. Spirulina is an algae known to ameliorate cardiometabolic disorders and with proven anti-inflammatory and anti-oxidant effects. We investigated, in a highly translatable animal model, whether oral supplementation with spirulina protects against the deleterious effects triggered by ST-elevation MI (STEMI). Methods: Pigs were fed a regular diet supplemented with spirulina (1 g/animal/bid) or placebo-control for 10 days. Thereafter, animals were subjected to 1.5 h percutaneous balloon-induced coronary occlusion (STEMI) followed by 2.5 h reperfusion and then sacrificed. We assessed infarct size and cardiac function. Blood samples and infarcted and remote myocardial tissue were obtained. Results: Spirulina supplementation reduced infarct size by 64%, increased myocardial salvage by 18%, and improved cardiac function by 30% vs. controls (p < 0.05). These benefits were associated with attenuation in DNA-oxidative damage and apoptotic markers and increased iNOS in the infarcted myocardium, higher AMPK activation in the remote myocardium, and lower myocardial MCP-1 expression. Systemically, spirulina attenuated Cox-2 expression in STEMI-activated peripheral blood mononuclear cells and enhanced TNF-α release acutely post-STEMI. Additionally, spirulina decreased weight gain progression over time (p < 0.05) without changes in lipids, glucose, liver or kidney parameters. Conclusion: A 10-day supplementation with spirulina exerts cardioprotection in a preclinical setting of STEMI by limiting cardiac damage and improving ventricular contractility through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms.

Reduced Heart Failure and Mortality in Patients Receiving Statin Therapy Before Initial Acute Coronary Syndrome.

BACKGROUND: There is uncertainty regarding the impact of statins on the risk of atherosclerotic cardiovascular disease (ASCVD) and its major complication, acute heart failure (AHF). OBJECTIVES: The aim of this study was to investigate whether previous statin therapy translates into lower AHF events and improved survival from AHF among patients presenting with an acute coronary syndrome (ACS) as a first manifestation of ASCVD. METHODS: Data were drawn from the International Survey of Acute Coronary Syndromes Archives. The study participants consisted of 14,542 Caucasian patients presenting with ACS without previous ASCVD events. Statin users before the index event were compared with nonusers by using inverse probability weighting models. Estimates were compared by test of interaction on the log scale. Main outcome measures were the incidence of AHF according to Killip class and the rate of 30-day all-cause mortality in patients presenting with AHF. RESULTS: Previous statin therapy was associated with a significantly decreased rate of AHF on admission (4.3% absolute risk reduction; risk ratio [RR]: 0.72; 95% CI: 0.62-0.83) regardless of younger (40-75 years) or older age (interaction P = 0.27) and sex (interaction P = 0.22). Moreover, previous statin therapy predicted a lower risk of 30-day mortality in the subset of patients presenting with AHF on admission (5.2 % absolute risk reduction; RR: 0.71; 95% CI: 0.50-0.99). CONCLUSIONS: Among adults presenting with ACS as a first manifestation of ASCVD, previous statin therapy is associated with a reduced risk of AHF and improved survival from AHF. (International Survey of Acute Coronary Syndromes [ISACS] Archives; NCT04008173).

Statins for primary prevention among elderly men and women.

AIMS: We undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations for statins translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly. METHODS AND RESULTS: We included in our analysis (ISACS Archives -NCT04008173) a total of 5619 Caucasian patients with no known prior history of CV disease who presented to hospital with a first manifestation of CV disease with age of 65 years or older. The risk of ST-segment elevation myocardial infarction (STEMI) was much lower in statin users than in non-users in both patients aged 65-75 years [14.7% absolute risk reduction; relative risk (RR): 0.55, 95% CI 0.45-0.66] and those aged 76 years and older (13.3% absolute risk reduction; RR: 0.58, 95% CI 0.46-0.72). Estimates were similar in patients with and without history of hypercholesterolaemia (interaction test; P-values = 0.24 and 0.35). Proportional reductions in STEMI diminished with female sex in the old (P for interaction = 0.002), but not in the very old age (P for interaction = 0.26). We also observed a remarkable reduction in the risk of 30 day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR: 0.39; 95% CI 0.23-0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR 0.37; 95% CI 0.17-0.82 for patients aged 65-75 years old; interaction test, P-value = 0.46). CONCLUSIONS: Preventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolaemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Randomized clinical trials may contribute to more definitively determine the role of statin therapy in the elderly.

SECURE, ADVOR and REVIVED: Clinical Trials Presented at ESC 2022.

In this article, three important clinical trials presented at the 2022 European Society of Cardiology Congress have been selected for a brief discussion. These are the SECURE, ADVOR and REVIVED-BCIS2 trials, all of which are investigator-initiated studies whose findings are of interest given their potential to impact clinical practice, ultimately improving current patient care and clinical outcomes.