The Role of C-reactive Protein in Patient Risk Stratification and Treatment

Atherosclerosis is a chronic inflammatory disease. Several circulating inflammatory markers have been proposed for clinical use due to their ability to predict future cardiovascular events and may be useful for identifying people at high risk who might benefit from specific treatment to reduce this risk. Moreover, the identification of new therapeutic targets will allow the development of drugs that can help reduce the high residual risk of recurrence of cardiovascular events in patients with coronary artery disease. The clinical benefits of reducing recurrent major cardiovascular events recently shown by canakinumab and colchicine have renewed the cardiology community’s interest in inflammation as an aetiopathogenic mechanism for atherosclerosis. This review explores the use of C-reactive protein, which is the most frequently studied biomarker in this context; the concept of residual risk in primary and secondary cardiovascular prevention; and the current recommendations in international guidelines regarding the role of this inflammatory biomarker in cardiovascular risk stratification

Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry

SARS-CoV-2; Reinfection; Respiratory complicationsSARS-CoV-2; Reinfección; Complicaciones respiratoriasSARS-CoV-2; Reinfecció; Complicacions respiratòriesBackground: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited. Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs. Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005). Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM

Post-COVID-19 Symptoms and Heart Disease: Incidence, Prognostic Factors, Outcomes and Vaccination: Results from a Multi-Center International Prospective Registry (HOPE 2)

COVID-19; Heart disease; PersistentCOVID 19; Malaltia cardíaca; PersistentCOVID-19; Enfermedad cardíaca; PersistenteBackground: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. Methods: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. Results: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81–3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04–0.19). Conclusions: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.Non-conditioned grant (Fundación Interhospitalaria para la Investigación cardiovascular, FIC. Madrid, Spain). This nonprofit institution had no role in the study design; collection, analysis, or interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19

COVID-19; Interstitial lung diseases; MortalityCOVID-19; Malalties pulmonars intersticials; MortalitatCOVID-19; Enfermedades pulmonares intersticiales; MortalidadBackground: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. Methods: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. Results: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. Conclusions: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score

Background: Long -term consequences of COVID-19 are still partly known. Aim of the study: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. Methods: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the CardioCovid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. Results: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60 +/- 16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1 -4 points for age class ( = 85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups ( 6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). Conclusions: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes—Results from a Multi-Center International Prospective Registry (HOPE-2)

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.S

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry

Background. Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods. Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results. 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion. Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score

COVID-19; Long-COVID; Prognostic scoreCOVID-19; COVID llarg; Puntuació pronòsticaCOVID-19; COVID largo; Puntuación pronósticaBackground Long-term consequences of COVID-19 are still partly known. Aim of the study To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. Methods 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. Results Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1–4 points for age class (<65 years, 65–74, 75–84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). Conclusions The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes—Results from a Multi-Center International Prospective Registry (HOPE-2)

COVID-19; Cardiomyopathy; TroponinCOVID-19; Miocardiopatia; TroponinaCOVID-19; Miocardiopatía; TroponinaBackground: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits