Bile Acids and Risk of Adverse Cardiovascular Events and All-Cause Mortality in Patients with Acute Coronary Syndrome.

The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12-1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

Immunoglobulins in COVID-19 pneumonia: from the acute phase to the recovery phase.

BACKGROUND: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. METHODS: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. RESULTS: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. CONCLUSIONS: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses.

Prevalence and prognostic implications of myocardial injury across different waves of COVID-19.

Introduction: The prognostic ability of myocardial injury across different waves of the COVID-19 pandemic is not well established. The purpose of this study was to evaluate the prevalence and prognostic implications of myocardial injury in the first and sixth wave of COVID-19. Methods: We conducted a retrospective observational study that included patients admitted to the emergency department with COVID-19 with data on concentrations of cardiac troponin during the first and sixth wave. We compared the prevalence of myocardial injury and its predictive capacity for 30-day all-cause death in both waves. Results and discussion: A total of 346 patients were included (1st wave 199 and 6th wave 147 patients). The prevalence of myocardial injury was 21% with non-significant differences between waves. Myocardial injury was associated, in both waves, with a higher prevalence of comorbidities and with an increased risk of 30-day all-cause death [1st wave HR: 3.73 (1.84-7.55); p < 0.001 and 6th wave HR: 3.13 (1.23-7.92); p = 0.016], with non-significant differences in predictive capacity between groups after ROC curve analysis [AUC: 1st wave 0.829 (95% CI: 0.764-0.895) and 6th wave 0.794 (95% CI: 0.711-0.876)]. As limitations, this is a retrospective study with a relatively small simple size and troponin assay was performed at the discretion of the emergency physician so selection bias could be present. In conclusion, the prevalence of myocardial injury and its prognostic capacity was similar in both waves despite vaccination programs. Myocardial injury predicts short-term mortality in all COVID-19 patients, so they should be treated intensively.

TCA cycle metabolites associated with adverse outcomes after acute coronary syndrome: mediating effect of renal function.

Aims: To examine relationships of tricarboxylic acid (TCA) cycle metabolites with risk of cardiovascular events and mortality after acute coronary syndrome (ACS), and evaluate the mediating role of renal function in these associations. Methods: This is a prospective study performed among 309 ACS patients who were followed for a mean of 6.7 years. During this period 131 patients developed major adverse cardiovascular events (MACE), defined as the composite of myocardial infarction, hospitalization for heart failure, and all-cause mortality, and 90 deaths were recorded. Plasma concentrations of citrate, aconitate, isocitrate, succinate, malate, fumarate, α-ketoglutarate and d/l-2-hydroxyglutarate were quantified using LC-tandem MS. Multivariable Cox regression models were used to estimate hazard ratios, and a counterfactual-based mediation analysis was performed to test the mediating role of estimated glomerular filtration rate (eGFR). Results: After adjustment for traditional cardiovascular risk factors and medications, positive associations were found between isocitrate and MACE (HR per 1 SD, 1.25; 95% CI: 1.03, 1.50), and between aconitate, isocitrate, d/l-2-hydroxyglutarate and all-cause mortality (HR per 1 SD, 1.41; 95% CI: 1.07, 1.84; 1.58; 95% CI: 1.23, 2.02; 1.38; 95% CI: 1.14, 1.68). However, these associations were no longer significant after additional adjustment for eGFR. Mediation analyses demonstrated that eGFR is a strong mediator of these associations. Conclusion: These findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications.

Plasma trimethylamine-N-oxide, its precursors and risk of cardiovascular events in patients with acute coronary syndrome: Mediating effects of renal function.

Aims: To examine associations of the gut microbial metabolite trimethylamine-N-oxide (TMAO) and its precursors with risk of cardiovascular events in acute coronary syndrome (ACS), and determine whether these associations were mediated by renal function. Methods: In this prospective cohort study, we included 309 patients with ACS. During a mean follow-up of 6.7 years, 131 patients developed major adverse cardiovascular events (MACE) (myocardial infarction, hospitalization for heart failure, and all-cause mortality). Plasma concentrations of TMAO, trimethylamine (TMA), choline, betaine, dimethylglycine and L-carnitine were profiled by liquid chromatography tandem mass spectrometry. Hazard ratios were estimated with multivariable Cox regression models. The mediating role of estimated glomerular filtration rate (eGFR) was tested under a counterfactual framework. Results: After adjustment for traditional cardiovascular risk factors and medications, participants in the highest tertile vs. the lowest tertile of baseline TMAO and dimethylglycine concentrations had a higher risk of MACE [(HR: 1.83; 95% CI: 1.08, 3.09) and (HR: 2.26; 95% CI: 1.17, 3.99), respectively]. However, with regards to TMAO these associations were no longer significant, whereas for dimethylglycine, the associations were attenuated after additional adjustment for eGFR. eGFR mediated the associations of TMAO (58%) and dimethylglycine (32%) with MACE incidence. The associations between dimethylglycine and incident MACE were confirmed in an internal validation. No significant associations were found for TMA, choline, betaine and L-carnitine. Conclusion: These findings suggest that renal function may be a key mediator in the association of plasma TMAO with the development of cardiovascular events after ACS. The present findings also support a role of dimethylglycine in the pathogenesis of MACE, which may be mediated, at least partially, by renal function.

Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.

Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier's Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case-control design. All of the included studies were of high quality according to the "Newcastle-Ottawa Scale". TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.

Performance of Coronary Angiography in the Detection of Coronary Artery Disease in Patients with Systolic Left Ventricular Dysfunction and No Prior Ischemic Heart Disease.

The diagnosis of ischemic cardiomyopathy is not well established. Our objective is to determine predictive variables of coronary disease in unselected patients with ventricular dysfunction. This study is a retrospective cohort study of consecutive patients with left ventricular dysfunction and no known history of ischemic heart disease. We analyse the demographic variables, clinical data, electrocardiogram, and echocardiogram that are associated with the presence of coronary stenosis on coronary angiography. A total of 536 patients with left ventricular dysfunction were studied, with 135 (25.2%) of them having significant coronary lesions. In the multivariate logistic regression analysis, age ≤ 50 years, female gender, and the presence of atrial fibrillation on the electrocardiogram (ECG) were predictors of the absence of coronary lesions. Diabetes, hypercholesterolemia, the existence of Q waves in the ECG, and segmental alterations in contractility in the echocardiogram were predictors of coronary heart disease (C-Statistics 0.771, 95% CI 0.727 to 0.814). The information obtained from the clinical history, the ECG, and the echocardiogram of patients with ventricular dysfunction allows us to select subjects in whom coronary angiography has shown poor performance in diagnosing coronary disease.

A simple combination of biomarkers for risk stratification in octogenarians with acute myocardial infarction.

The aim of this observational study was to assess long-term prognosis of a contemporary octogenarian population admitted to an Intensive Cardiac Care Unit with acute myocardial infarction (MI), and the prognostic value of two simple biomarkers obtained at admission: glucose blood level (ABG) and estimated glomerular filtration rate (eGFR). A total of 293 consecutive patients were included (202 with ST elevation MI and 91 with non-ST elevation MI) with median age 83.9 years, 172 (58.7%) male. The optimal cut-off points for all-cause death defined by ROC curves were ABG >186 mg/dL and eGFR <50 mL/min/1.73 m2. The cohort was segregated into 3 groups according to these values: no biomarker present (group 1), either of the two biomarkers present (group 2) or both biomarkers present (group 3). Patients in group 3 were more frequently female, with worse Charlson index, Killip class and ventricular function, and higher GRACE scores. PCI was performed in 248 patients (84.6%). The highest in-hospital and long-term mortality, and composite MACE was observed in groups 2 and 3. All-cause mortality (median follow-up 2.2 years) was 44%. In multivariate analysis, ABG >186 mg/dL and eGFR <50 mL/min/1.73 m2 were associated with a 4.2 odds ratio (OR) (Model 1: medical history variables) and 2.6 OR (Model 2: admission event variables) of mortality. The addition of these variables to ROC curves improved long-term risk prediction for Model 1 (C-statistics 0.718 versus 0.780, p = 0.006) and reclassification and discrimination in both models.

Clinical characteristics and prognostic implications of diabetes and myocardial injury in patients admitted to the emergency room.

BACKGROUND: This study aimed to investigate the clinical features and prognosis of diabetes and myocardial injury in patients admitted to the emergency department. METHODS: We analyzed the clinical data of all consecutive patients admitted to the emergency department during the years 2012 and 2013 with at least 1 cardiac Troponin I (cTnI Ultra Siemens, Advia Centaur) determination, and were classified according to the status of diabetes mellitus (DM) and myocardial injury (MI). Clinical events were evaluated in a 4-year follow-up. RESULTS: A total of 3622 patients were classified according to the presence of DM (n = 924 (25.55%)) and MI (n = 1049 (28.96%)). The proportion of MI in patients with DM was 40% and 25% in patients without DM. Mortality during follow-up was 10.9% in non-DM patients without MI, 21.3% in DM patients without MI, 40.1% in non-DM patients with MI, and 52.8% in DM patients with MI. A competitive risk model was used to obtain the Hazard Ratio (HR) for readmission for myocardial infarction or heart failure. There was a similar proportion of readmission for myocardial infarction and heart failure at a four-year follow-up in patients with DM or MI, which was much higher when DM was associated with MI, with respect to patients without DM or MI. The HR (95% Coefficient Interval) for myocardial infarction in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2511 (1592-3960), 2682 (1739-4138), and 5036 (3221-7876), respectively. The HR (95% CI) for the risk of readmission for heart failure in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2663 (1825-3886), 2562 (1753-3744) and 4292 (2936-6274), respectively. CONCLUSIONS: The association of DM and MI in patients treated in an Emergency Service identifies patients at very high risk of mortality and cardiovascular events.

Biomarkers and short-term prognosis in COVID-19.

PURPOSE: The aim of our study was to analyse the short-term prognostic value of different biomarkers in patients with COVID-19. METHODS: We included patients admitted to emergency department with COVID-19 and available concentrations of cardiac troponin I (cTnI), D-dimer, C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients were classified for each biomarker into two groups (low vs. high concentrations) according to their best cut-off point, and 30-day all-cause death was evaluated. RESULTS: After multivariate adjustment, cTnI ≥21 ng/L, D-dimer ≥1112 ng/mL, CRP ≥10 mg/dL and LDH ≥334 U/L at admission were associated with an increased risk of 30-day all-cause death (hazard ratio (HR) 4.30; 95% CI 1.74-10.58; p = 0.002; HR 3.35; 95% CI 1.58-7.13; p = 0.002; HR 2.25; 95% CI 1.13-4.50; p = 0.021; HR 2.00; 95% CI 1.04-3.84; p = 0.039, respectively). The area under the curve for cTnI was 0.825 (95% CI 0.759-0.892) and, in comparison, was significantly better than CRP (0.685; 95% CI 0.600-0.770; p = 0.009) and LDH (0.643; 95% CI 0.534-0.753; p = 0.006) but non-significantly better than D-dimer (0.756; 95% CI 0.674-0.837; p = 0.115). CONCLUSIONS: In patients with COVID-19, increased concentrations of cTnI, D-dimer, CRP and LDH are associated with short-term mortality. Of these, cTnI provides better mortality risk prediction. However, differences with D-dimer were non-significant.

[Prognostic implications of myocardial injury in patients with and without COVID-19 infection treated in a university hospital]. / Implicaciones pronósticas del daño miocárdico en pacientes con y sin diagnóstico confirmado de COVID-19 atendidos en un hospital universitario.

INTRODUCTION AND OBJECTIVES: Cardiac troponin, a marker of myocardial injury, is frequently observed in patients with COVID-19 infection. Our objective was to analyze myocardial injury and its prognostic implications in patients with and without COVID-19 infection treated in the same period of time. METHODS: The present study included patients treated in a university hospital with cardiac troponin I measurements and with suspected COVID-19 infection, confirmed or ruled out by polymerase chain reaction analysis. The impact was analyzed of cardiac troponin I positivity on 30-day mortality. RESULTS: In total, 433 patients were distributed among the following groups: confirmed COVID-19 (n = 186), 22% with myocardial injury (n = 41); and ruled out COVID-19 (n = 247), 21.5% with myocardial injury (n = 52). The confirmed and ruled out COVID-19 groups had a similar age, sex, and cardiovascular history. Mortality was significantly higher in the confirmed COVID-19 group than in the ruled out group (19.9% vs 5.3%, P < .001). In Cox multivariate regression analysis, cardiac troponin I was a predictor of mortality in both groups (confirmed COVID-19 group: HR, 3.54; 95%CI, 1.70-7.34; P = .001; ruled out COVID-19 group: HR, 5.57; 95%CI, 1.70-18.20; P = .004). The predictive model analyzed by ROC curves was similar in the 2 groups (P = .701), with AUCs of 0.808 in the confirmed COVID-19 group (0.750-0.865) and 0.812 in the ruled out COVID-19 group (0.760-0.864). CONCLUSIONS: Myocardial injury is detected in 1 in every 5 patients with confirmed or ruled out COVID-19 and predicts 30-day mortality to a similar extent in both circumstances.

Prognostic implications of myocardial injury in patients with and without COVID-19 infection treated in a university hospital.

INTRODUCTION AND OBJECTIVES: Cardiac troponin, a marker of myocardial injury, is frequently observed in patients with COVID-19 infection. Our objective was to analyze myocardial injury and its prognostic implications in patients with and without COVID-19 infection treated in the same period of time. METHODS: The present study included patients treated in a university hospital with cardiac troponin I measurements and with suspected COVID-19 infection, confirmed or ruled out by polymerase chain reaction analysis. The impact was analyzed of cardiac troponin I positivity on 30-day mortality. RESULTS: In total, 433 patients were distributed among the following groups: confirmed COVID-19 (n=186), 22% with myocardial injury (n=41); and ruled out COVID-19 (n=247), 21.5% with myocardial injury (n=52). The confirmed and ruled out COVID-19 groups had a similar age, sex, and cardiovascular history. Mortality was significantly higher in the confirmed COVID-19 group than in the ruled out group (19.9% vs 5.3%, P <.001). In Cox multivariate regression analysis, cardiac troponin I was a predictor of mortality in both groups (confirmed COVID-19 group: HR, 3.54; 95%CI, 1.70-7.34; P=.001; ruled out COVID-19 group: HR, 5.57; 95%CI, 1.70-18.20; P=.004). The predictive model analyzed by ROC curves was similar in the 2 groups (P=.701), with AUCs of 0.808 in the confirmed COVID-19 group (0.750-0.865) and 0.812 in the ruled out COVID-19 group (0.760-0.864). CONCLUSIONS: Myocardial injury is detected in 1 in every 5 patients with confirmed or ruled out COVID-19 and predicts 30-day mortality to a similar extent in both circumstances.

Lack of Association of Initial Viral Load in SARS-CoV-2 Patients with In-Hospital Mortality.

Controversy exists in the literature regarding the possible prognostic implications of the nasopharyngeal SARS-CoV-2 viral load. We carried out a retrospective observational study of 169 patients, 96 (58.9%) of whom had a high viral load and the remaining had a low viral load. Compared with patients with a low viral load, patients with a high viral load did not exhibit differences regarding preexisting cardiovascular risk factors or comorbidities. There were no differences in symptoms, vital signs, or laboratory tests in either group, except for the maximum cardiac troponin I (cTnI), which was higher in the group with a higher viral load (24 [interquartile range 9.5-58.5] versus 8.5 [interquartile range 3-22.5] ng/L, P = 0.007). There were no differences in the need for hospital admission, admission to the intensive care unit, or the need for mechanical ventilation in clinical management. In-hospital mortality was greater in patients who had a higher viral load than in those with low viral load (24% versus 10.4%, P = 0.029). High viral loads were associated with in-hospital mortality in the binary logistic regression analysis (odds ratio: 2.701, 95% Charlson Index (CI): 1.084-6.725, P = 0.033). However, in an analysis adjusted for age, gender, CI, and cTnI, viral load was no longer a predictor of mortality. In conclusion, an elevated nasopharyngeal viral load was not a determinant of in-hospital mortality in patients with COVID-19, as much as age, comorbidity, and myocardial damage determined by elevated cTnI are.

Stromal cell derived factor-1 and long-term prognosis in acute coronary syndrome.

Aim: To explore long-term prognostic value of SDF-1 in acute coronary syndrome (ACS). Materials & methods: We included 254 patients with ACS. Plasma SDF-1 was measured and patients were classified into tertiles of SDF-1. Results: Multivariate analysis showed third tertile of SDF-1 as an independent predictor of all-cause death (HR: 2.5; 95% CI: 1.2-5.2; p = 0.011) and the composite of major adverse cardiovascular and cerebrovascular events (HR: 1.8; 95% CI: 1.1-3.1; p = 0.031). SDF-1 added to a clinical model can improve all-cause death prediction (net reclassification improvement 0.362; 95% CI: 0.423-0.681; p = 0.027). Conclusion: SDF-1 is an independent predictor of all-cause mortality and major adverse cardiovascular and cerebrovascular events in long-term follow-up of patients with ACS and adds prognostic information beyond traditional cardiovascular risks factors.

Long-term prognostic value of growth differentiation factor-15 in acute coronary syndromes.

BACKGROUND: Growth Differentiation Factor-15 (GDF-15) predicts death and cardiovascular events in acute coronary syndromes (ACS). We aimed to assess the long-term prognostic value of GDF-15 in ACS. METHODS: We included 358 patients with ACS who underwent coronary angiography. Plasma GDF-15 was measured and clinical data and long-term events were registered. Incremental value of GDF-15 for prognosing all-cause death above a clinical model including GRACE score, left ventricular ejection fraction <40%, prior myocardial infarction and age was assessed. RESULTS: GDF-15 concentrations >1800 ng/L were associated with an increased prevalence of cardiovascular risk factors. During 6.5 years of follow-up 56 patients died, 7 had values of GDF-15 < 1200 ng/L, 7 between 1200 and 1800 ng/L and 42 > 1800 ng/L. After adjustment for potential confounders, GDF-15 > 1800 ng/L were independently associated with all-cause death (HR 4.09; 95% CI 1.57-10.71; p = .004) and the composite of major adverse cardiovascular events (MACE) (HR 2.48; 95% CI 1.41-4.34; p = .001). For long-term all-cause death a significant increase of ROC curve was seen after addition of GDF-15 to a clinical model 0.876 (95% CI 0.823-0.928; p = .014). Same improvements were found for net reclassification improvement (0.776; 95% CI 0.494-1.037; p < .001) and integrated discrimination improvement (0.112; 95% CI 0.055-0.169; p < .001). Multivariate competing risk model showed a significant association between GDF-15 > 1800 ng/L and the incidence of heart failure but not of myocardial infarction. CONCLUSIONS: In the setting of ACS, GDF-15 is associated with long-term all-cause death, MACE and heart failure and provides incremental prognostic value beyond traditional risks factor.