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.
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.
This study aimed to investigate the clinical features and prognosis of diabetes and myocardial injury in patients admitted to the emergency department.
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.
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.
The association of DM and MI in patients treated in an Emergency Service identifies patients at very high risk of mortality and cardiovascular events.
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.
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).
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.
These findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications.
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.
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.
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);
< 0.001 and 6th wave HR: 3.13 (1.23-7.92);
= 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.
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.
Myocardial injury, which is present in >20% of patients hospitalized for COVID-19, is associated with increased short-term mortality, but little is known about its mid- and long-term consequences. We ...evaluated the association between myocardial injury with one-year mortality and readmission in 172 COVID-19 patients discharged alive. Patients were grouped according to the presence or absence of myocardial injury (defined by hs-cTn levels) on admission and matched by age and sex. We report mortality and hospital readmission at one year after admission in all patients and echocardiographic, laboratory and clinical data at six months in a subset of 86 patients. Patients with myocardial injury had a higher prevalence of hypertension (73.3% vs. 50.0%,
= 0.003), chronic kidney disease (10.5% vs. 2.35%,
= 0.06) and chronic heart failure (9.3% vs. 1.16%,
= 0.03) on admission. They also had higher mortality or hospital readmissions at one year (11.6% vs. 1.16%,
= 0.01). Additionally, echocardiograms showed thicker walls in these patients (10 mm vs. 8 mm,
= 0.002) but without functional disorder. Myocardial injury in COVID-19 survivors is associated with poor clinical prognosis at one year, independent of age and sex, but not with echocardiographic functional abnormalities at six months.
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.
To identify patients with type 2 myocardial infarction (MI) and patients with non-ischaemic myocardial injury (NIMI) and to compare their prognosis with those of patients with type 1 MI.
A ...retrospective observational study was performed in 1010 patients admitted to the emergency department of a university hospital with at least one troponin I test between 2012 and 2013. Participants were identified using laboratory records and divided into three groups: type 1 MI (rupture of atheromatous plaque), type 2 MI (imbalance between myocardial oxygen supply and/or demand) and NIMI (patients who did not meet diagnostic criteria for type 1 or type 2 MI). Clinical characteristics and 2-year outcomes were analysed.
Patients with type 2 MI and NIMI were older, with higher proportion of women and more comorbidities than patients with type 1 MI. Absolute mortality and the adjusted risk for all-cause mortality in both groups were significantly higher than that of patients with type 1 MI (39.7%, HR: 1.41 95% CI 1.02 to 1.94, p=0.038 and 40.0%, HR: 1.54 95% CI 1.16 to 2.04, p=0.002, respectively). Patients with type 2 MI and NIMI tended to present more readmissions due to heart failure (16.5%, HR: 1.55 95% CI 0.87 to 2.76, p=0.133 and 12.3%, HR: 1.15 95% CI 0.70 to 1.90, p=0.580) and less readmission rates due to acute coronary syndrome (ACS) than patients with type 1 MI (2.1%, HR: 0.11 95% CI 0.04 to 0.31, p<0.001 and 4.3%, HR: 0.22 95% CI 0.12 to 0.41, p<0.001), CONCLUSIONS: Patients diagnosed with type 2 MI and NIMI have higher rates of mortality and lower readmission rates for ACS compared with patients with type 1 MI.
•The TARRACO Risk Score incorporates cardiac troponin and clinical predictors of adverse cardiovascular events (ie, age, hypertension, absence of chest pain, dyspnea, and anemia).•This risk score ...showed good discriminative accuracy for patients with type 2 myocardial infarction and patients with myocardial injury (area under the curve = 0.75 and 0.74, respectively).•Prognosis in type 2 myocardial infarction could efficiently be estimated early, prior to hospital discharge.
Despite adverse prognoses of type 2 myocardial infarction and myocardial injury, an effective, practical risk stratification method remains an unmet clinical need. We sought to develop an efficient clinical bedside tool for estimating the risk of major adverse cardiovascular events at 180 days for this patient population.
The derivation cohort included patients with type 2 myocardial infarction or myocardial injury admitted to a tertiary hospital between 2012 and 2013 (n = 611). The primary outcome was a major adverse cardiovascular event (death or readmission for heart failure or myocardial infarction). The score included clinical variables significantly associated with the outcome. External validation was conducted using the UTROPIA cohort (n = 401).
The TARRACO Score included cardiac troponin (cTn) concentrations and 5 independent clinical predictors of adverse cardiovascular events: age, hypertension, absence of chest pain, dyspnea, and anemia. The score exhibited good discriminative accuracy (area under the curve = 0.74; 95% CI, 0.70-0.79). Patients were classified into low-risk (score 0-6) and high-risk (score ≥7) categories. Major adverse cardiovascular events rates were 5 times more likely in high-risk patients compared with those at low risk (78.9 vs 15.4 events/100 patient-years, respectively; logrank P < .001). The external validation showed equivalent prognostic capacity (area under the curve=0.71, 0.65-0.78).
A novel risk score based on bedside clinical variables and cTn concentrations allows risk stratification for death and cardiac-related rehospitalizations in patients with type 2 myocardial infarctions and myocardial injury. This score identifies patients at the highest risk of adverse events, a subset of patients who may benefit from close observation, medical intensification, or both.
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