Classification tree obtained by artificial intelligence for the prediction of heart failure after acute coronary syndromes. / Árboles de clasificación obtenidos mediante inteligencia artificial para la predicción de insuficiencia cardiaca tras el síndrome coronario agudo.

BACKGROUND: Coronary heart disease is the leading cause of heart failure (HF), and tools are needed to identify patients with a higher probability of developing HF after an acute coronary syndrome (ACS). Artificial intelligence (AI) has proven to be useful in identifying variables related to the development of cardiovascular complications. METHODS: We included all consecutive patients discharged after ACS in two Spanish centers between 2006 and 2017. Clinical data were collected and patients were followed up for a median of 53months. Decision tree models were created by the model-based recursive partitioning algorithm. RESULTS: The cohort consisted of 7,097 patients with a median follow-up of 53months (interquartile range: 18-77). The readmission rate for HF was 13.6% (964 patients). Eight relevant variables were identified to predict HF hospitalization time: HF at index hospitalization, diabetes, atrial fibrillation, glomerular filtration rate, age, Charlson index, hemoglobin, and left ventricular ejection fraction. The decision tree model provided 15 clinical risk patterns with significantly different HF readmission rates. CONCLUSIONS: The decision tree model, obtained by AI, identified 8 leading variables capable of predicting HF and generated 15 differentiated clinical patterns with respect to the probability of being hospitalized for HF. An electronic application was created and made available for free.

Applicability of the Zwolle score for selection of very high-risk ST-elevation myocardial infarction patients treated with primary angioplasty.

The Zwolle risk score was designed to stratify in-hospital mortality risk of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI) and for decision-making in the unit where patients are admitted. We assessed the accuracy of Zwolle risk score for in-hospital mortality estimation compared with the GRACE score in all patients (n = 4446) admitted for STEMI in 3 university hospitals. Only one fourth of the patients were classified as high-risk by the Zwolle risk score vs 60% by the GRACE score. In-hospital mortality was 10.6%. A statistically significant increase in in-hospital mortality, adjusted by age, gender, and revascularization, was observed with both scores. The assessment of the optimal cut-off points verified the accuracy of Zwolle score ≥4 as optimal threshold for high-risk categorization. In contrast, GRACE score ≥140 had very low specificity as well as percentage of patients correctly classified; GRACE score ≥175 was fairly better. The reclassification index of the Zwolle score after applying the GRACE score was 35.5%. Selection of high-risk STEMI patients treated with pPCI based on the Zwolle risk score has higher specificity than the GRACE score and might be useful in clinical practice.

Soluble angiotensin-converting enzyme levels in heart failure or acute coronary syndrome: revisiting its modulation and prognosis value.

The main objective was to compare the meaning of soluble angiotensin-converting enzyme-2 (sACE2) plasma levels modulation on the prognosis of two cohorts of heart failure (HF) and acute coronary syndrome (ACS). We conducted an observational clinical study where sACE2 was measured in two cohorts of HF or ACS (102 patients each), matched by age and gender. The primary endpoint (cardiac death) and the secondary endpoints (non-fatal myocardial infarction or HF readmission) were registered during a 5-year follow-up period. Association with pharmacotherapy was studied, and the effects of cardiovascular drugs on ACE isoforms expression were analysed in human umbilical vein endothelial cells (HUVEC) in vitro. The levels of sACE2 were significantly higher in the HF than ACS cohort. sACE2 was inversely related with the leukocytes number and directly with urea levels. In the ACS cohort, sACE2 was associated with age and glycaemic parameters, but in the HF cohort, the association was with N-terminal pro-B-type natriuretic peptide. The levels of sACE2 were related to long-term prognosis and confirmed as a non-independent predictor in the HF cohort. Soluble ACE2 was higher in patients treated with angiotensin receptors blockers and ß-blockers, accordingly with losartan and metoprolol upregulation of ACE1 and ACE2 in HUVECs. Plasma levels of sACE2 were higher in HF than in ACS, independently of age and gender, and were related to long-term cardiac death in the HF cohort. Losartan and metoprolol, but not enalapril, upregulated ACE expression in endothelial cells, accordingly with higher levels of sACE2 in patients using these drugs.

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.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

Prediction of major adverse cardiac, cerebrovascular events in patients with diabetes after acute coronary syndrome.

BACKGROUND AND OBJECTIVES: The risk of major adverse cardiac and cerebrovascular events following acute coronary syndrome is increased in people with diabetes. Predicting out-of-hospital outcomes upon follow-up remains difficult, and no simple, well-validated tools exist for this population at present. We aim to evaluate several factors in a competing risks model for actionable evaluation of the incidence of major adverse cardiac and cerebrovascular events in diabetic outpatients following acute coronary syndrome. METHODS: Retrospective analysis of consecutive patients admitted for acute coronary syndrome in two centres. A Fine-Gray competing risks model was adjusted to predict major adverse cardiac and cerebrovascular events and all-cause mortality. A point-based score is presented that is based on this model. RESULTS: Out of the 1400 patients, there were 783 (55.9%) with at least one major adverse cardiac and cerebrovascular event (417 deaths). Of them, 143 deaths were due to non-major adverse cardiac and cerebrovascular events. Predictive Fine-Gray models show that the 'PG-HACKER' risk factors (gender, age, peripheral arterial disease, left ventricle function, previous congestive heart failure, Killip class and optimal medical therapy) were associated to major adverse cardiac and cerebrovascular events. CONCLUSION: The PG-HACKER score is a simple and effective tool that is freely available and easily accessible to physicians and patients. The PG-HACKER score can predict major adverse cardiac and cerebrovascular events following acute coronary syndrome in patients with diabetes.

The different roles for the advanced glycation end products axis in heart failure and acute coronary syndrome settings.

AIMS: This work aimed to compare the behavior of the advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in two cohorts of patients: those with heart failure (HF) and acute coronary syndrome (ACS). METHODS AND RESULTS: A unicentric observational clinical study was performed in 102 patients with ACS and 102 patients with chronic HF matched by age and gender. At inclusion, fluorescent AGEs were measured by quantitative fluorescence spectroscopy of plasma, and total sRAGE and endogenous secretory RAGE (esRAGE) levels were determined by enzyme-linked immunosorbent assay kits. A 5-year follow-up period was established for recording cardiac death (primary endpoint) and the incidence of non-fatal myocardial infarction or HF readmission (secondary endpoints). Higher glycation parameters were observed in HF patients, whereas no differences in sRAGE forms were found between HF and ACS cohorts, except for cRAGE, which was higher in HF. Associations between glycation parameters and sRAGE forms were observed in HF, but not in ACS. Differences were also evidenced in the long-term prognosis of each cohort: esRAGE showed an independent prognostic value for cardiac death or non-fatal cardiovascular events in HF, but none of the AGE-RAGE variables were predictors in ACS. CONCLUSIONS: A different role for the AGE-RAGE axis was observed in HF and ACS. All the sRAGE forms were directly related with glycation parameters in HF, but not in ACS. The independent value of the sRAGE forms on each cardiovascular disease was supported by esRAGE being an independent predictor of bad long-term prognosis only for HF.

Clinical impact of mineralocorticoid receptor antagonists treatment after acute coronary syndrome in the real world: A propensity score matching analysis.

BACKGROUND: Recent studies suggest that the benefit of mineralocorticoid receptor antagonists in the acute coronary syndrome setting is controversial. The aim of this study was to examine the current long-term prognostic benefit of mineralocorticoid receptor antagonists in patients with acute coronary syndrome. MATERIAL AND METHODS: We conducted a retrospective cohort study of 8318 consecutive acute coronary syndrome patients. Baseline patient characteristics were examined and a follow-up period was established for registry of death, major cardiovascular adverse events and heart failure re-hospitalization. We performed a propensity-matching analysis to draw up two groups of patients paired according to whether or not they had been treated with mineralocorticoid receptor antagonists. The prognostic value of mineralocorticoid receptor antagonists to predict events during follow-up was analysed using Cox regression. RESULTS: Among the study participants, only 524 patients (6.3%) were discharged on mineralocorticoid receptor antagonists. Patients on mineralocorticoid receptor antagonists had a different clinical and pharmacological profile. These differences disappeared after the propensity score analysis. The median follow-up was 40.7 months. After the propensity score analysis, the cardiovascular mortality and heart failure readmission rates were similar between patients who were discharged on mineralocorticoid receptor antagonists and those whose not. The use of mineralocorticoid receptor antagonists was only associated with a reduction in major cardiovascular adverse events (hazard ratio=0.83, 95% confidence interval 0.69-0.97, p=0.001). CONCLUSIONS: Our results do not corroborate the long-term benefit of mineralocorticoid receptor antagonists to improve survival after acute coronary syndrome in a large cohort of patients with heart failure or reduced left ventricular ejection fraction and diabetes. Their prescription was associated with a significantly lower incidence of major cardiovascular adverse events during the long-term follow-up without effect on heart failure development.

Incidence and predictors of stroke in patients discharged with the diagnosis of acute coronary syndrome.

BACKGROUND: Stroke is one the most feared cardiovascular disease due to its high risk of disability and its incidence after an acute coronary syndrome (ACS) is not uncommon. METHODS: Retrospective study of all consecutive patients admitted for an ACS in two hospitals. Competing risk regression, taking all-cause mortality as a competing event, was used for the assessment of stroke incidence. RESULTS: We included 8771 patients, AF prevalence 12.4%. AF patients were older and presented higher prevalence of cardiovascular risk factors, previous cardiovascular disease, and lower glomerular filtration rate. Less than half of AF patients were receiving oral anticoagulation before admission. In-hospital mortality was 5.1% and it was more than two-fold higher in AF patients (10.2% vs. 4.4%; p < 0.01). Relevant differences on medical treatments were observed at discharge and oral anticoagulation was roughly <50% in AF patients. During a median follow-up was 58.7 months, 313 patients experienced at least one stroke (incidence 3.8%, 95% CI 3.4-4.2,) and it was 2-fold higher in patients with AF: 7.8% vs. 3.3% (p < 0.01). Median time to first stroke was 33.0 (30.1) months and it was shorter for AF patients compared to non-AF patients (28.2 ±â€¯22.3 vs. 34.6 ±â€¯31.1; p < 0.01). The adjusted competing risk regression identified AF, previous stroke and CHA2DS2-VASc score = 2 or ≥3 as independent predictors of stroke; CHA2DS2-VASc score = 2 was associated to higher risk of stroke only in AF patients. CONCLUSIONS: The long-term incidence of stroke after an ACS was 3.8%, 7.8% in AF-patients and 3.3% in patients without any diagnosis of AF.

A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial.

PURPOSE: To obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA). METHODS: We designed a multicentre pilot trial with 1:1:1 randomization to either 32 °C (n = 52), 33 °C (n = 49) or 34 °C (n = 49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of ≤ 3, blindly assessed at 90 days. RESULTS: At baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 °C (13.5%), 33 °C (34.7%) and 34 °C (28.6%; p = 0.03). The percentage of patients with an mRS ≤ 3 at 90 days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 °C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90 days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 °C, respectively (trend test p = 0.04). All levels of cooling were well tolerated. CONCLUSIONS: There were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 °C. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov unique identifier: NCT02035839 ( http://clinicaltrials.gov ).

Prevalence, long-term prognosis and medical alternatives for patients admitted for acute coronary syndromes and prasugrel contraindication.

BACKGROUND: Prasugrel is a potent antiplatelet therapy that has demonstrated to be superior to clopidogrel for patients with acute coronary syndromes (ACS) but has three main contraindications. METHODS: Prospective study of all patients admitted for ACS in two hospitals. Prasugrel contraindication group was defined by the presence of age >75 years, weight <60 kg or previous stroke. We also performed a propensity score matching to obtain a well-balanced subset of patients with the same probability of receiving ticagrelor. RESULTS: We included 8207 patients and 2538 (30.9%) had any contraindication for prasugrel, being age >75 years the most frequent (29.0%). Hospital mortality was 4.4% and it was >2-fold higher in patients with any contraindication for prasugrel (7.9% vs. 2.8%; p < 0.01). Postdischarge follow-up (median 59.9 months) revealed that patients with prasugrel contraindication had higher cardiovascular and all-cause mortality as well as a first major cardiovascular event (MACE). No differences in bleeding rates were found in patients with vs. without prasugrel contraindication. Prasugrel contraindication was independently associated to higher cardiovascular (HR: 1.42) and all-cause mortality (HR: 1.47), as well as higher MACE (HR: 1.25). In the sub-cohort of 482 pairs of patients, obtained by a propensity score matching, ticagrelor treatment was associated with lower cardiovascular death (HR: 0.22), all-cause mortality (HR: 0.30) and first MACE (HR: 0.58) in patients with prasugrel contraindication. CONCLUSIONS: Almost one third of ACS patients have prasugrel contraindications and they have worst in in-hospital and post-discharge prognosis. Ticagrelor improved postdischarge outcomes in patients with prasugrel contraindications.

Determinants and Prognostic Impact of Heart Failure and Left Ventricular Ejection Fraction in Acute Coronary Syndrome Settings.

INTRODUCTION AND OBJECTIVES: Contemporary data on the incidence and prognosis of heart failure (HF) and the influence of left ventricular ejection fraction (LVEF) in the setting of acute coronary syndrome (ACS) are scant. The aim of this study was to examine the relationship between LVEF and HF with long-term prognosis in a cohort of patients with ACS. METHODS: This is a retrospective observational study of 6208 patients consecutively admitted for ACS to 2 different Spanish hospitals. Baseline characteristics were examined and a follow-up period was established for registration of death and HF rehospitalization as the primary endpoint. RESULTS: Among the study participants, 5064 had ACS without HF during hospitalization: 290 (5.8%) had LVEF<40%, 540 (10.6%) LVEF 40% to 49%, and 4234 (83.6%) LVEF ≥ 50%. The remaining 1144 patients developed HF in the acute phase: 395 (34.6%) had LVEF<40%, 251 (21.9%) LVEF 40% to 49%, and 498 (43.5%) LVEF ≥ 50%. Patients with LVEF 40% to 49% had a demographic and clinical profile with intermediate features between the LVEF <40% and LVEF ≥ 50% groups. Kaplan-Meier curves showed that mortality and HF readmissions were statistically different depending on LVEF in the non-HF group but not in the HF group. Left ventricular ejection fraction ≥ 50% was an independent prognostic factor in the non-HF group only. CONCLUSIONS: In ACS, long-term prognosis is considerably worse in patients who develop HF during hospitalization than in patients without HF, irrespective of LVEF. This parameter is a strong prognostic predictor only in patients without HF.

Additive value of the CRUSADE score to the GRACE score for mortality risk prediction in patients with acute coronary syndromes.

INTRODUCTION: Acute coronary syndrome (ACS) treatments increase bleeding complications that also impair prognosis. Bleeding risk scores reclassification of actual mortality risk estimated by the GRACE score might improve overall estimation. METHODS: Observational and prospective study of all ACS patients admitted in two hospitals. Mortality risk was assessed by the GRACE score and bleeding risk by the CRUSADE score. We analyzed the net reclassification improvement (NRI) of adding the CRUSADE score to the GRACE score. RESULTS: We included 6997 patients, mean age 67.4 (12.9), 38.0% ST-elevation ACS, mean GRACE score 145.2 (39.9). The percentage of patients with CRUSADE score >20 or >50 increased as the GRACE score was higher. Hospital mortality was 5.3% and the addition of the CRUSADE score reclassified a relevant percentage of patients with GRACE score >109; NRI was 3.80% (1.10-6.10). During follow-up, (median 53.0months) mortality rate was 22.6% and patients with CRUSADE score >50 had significantly higher mortality rates in all GRACE score categories; NRI was high (46.6%, 95% CI 41.0-53.1). The multivariate analysis outlined the independent predictive value of CRUSADE score >20 or >50 as well as GRACE scores 109-139 and >140. CONCLUSIONS: The addition of the CRUSADE score to the GRACE score improved mortality risk estimation. A CRUSADE score >50 identified patients with higher post-discharge mortality and higher hospital mortality if GRACE score was >109. The CRUSADE score improved hospital and long-term mortality prediction in patients with GRACE score >140. Individual mortality risk estimation should integrate the CRUSADE and GRACE scores.

The Risk of Cardiovascular Events After an Acute Coronary Event Remains High, Especially During the First Year, Despite Revascularization.

INTRODUCTION AND OBJECTIVES: There is little information on the incidence and predictors of infarction, stroke, or cardiovascular death after acute coronary syndrome. We investigated these aspects and developed tools for predicting these events according to the time of their occurrence. METHODS: A retrospective study was conducted of 4858 patients who survived an acute coronary event. We analyzed the incidence and predictors of acute myocardial infarction, stroke, or cardiovascular death during the first year (n=4858) vs successive years (n=4345 patients free of composite events during the first year). RESULTS: There were 329 events in the first year (cumulative incidence function: 7.3% person-years) and 616 in successive years (21.5% person-years; follow-up 4.9±2.4 years). The risk of events during the first year per tertile was 2.5% person-years in the low-risk tertile (< 3 points), 4.8% person-years in the intermediate-risk tertile (3-6 points), and 15.5% person-years in the high-risk tertile (> 6 points) (P<.001). The risk of events in the cohort that had a combined event in successive years increased from 10.7% person-years in the low-risk tertile (< 3 points) to 40.3% person-years in the high-risk tertile (> 6 points) (P<.001). The 2 scales showed the following predictive indexes: C statistic, 0.74 and 0.69, respectively; P (Hosmer-Lemeshow test)≥0.44 CONCLUSION: The risk of recurrence of cardiovascular events remains high after acute coronary syndrome. The level of risk can be easily quantified with acceptable predictive ability.

Advanced glycation end-products as long-term predictors of death and reinfarction after an acute coronary syndrome.

AIM: We evaluated the prognostic value of plasmatic fluorescent advanced glycation end-products (AGE) to predict long-term death and reinfarction in patients with acute coronary syndrome (ACS). MATERIALS & METHODS: A unicenter registry comprising a prospective cohort of 210 ACS patients (47.4% ST-segment elevation myocardial infarction) followed up during 3.1 ± 0.9 years were carried out. RESULTS: Cardiovascular death ratio was 5.7% and 23 patients suffered reinfarction (11.0%). The hazard ratio of the multivariate analysis with respect to death and reinfarction for AGE adjusted by GRACE risk score was 1.011 (1.006-1.016), p < 0.001. CONCLUSION: Fluorescent AGE plasma levels were an independent predictor of death and reinfarction in the long-term follow-up of patients with ACS.

Fluorescent advanced glycation end products and their soluble receptor: the birth of new plasmatic biomarkers for risk stratification of acute coronary syndrome.

OBJECTIVE: Advanced glycation end products (AGEs) have pathophysiological implications in cardiovascular diseases. The aim of our study was to evaluate the prognostic value of fluorescent AGEs and its soluble receptor (sRAGE) in the context of acute coronary syndrome (ACS), both in-hospital phase and follow-up period. METHODS: A prospective clinical study was performed in patients with debut's ACS. The endpoints were the development of cardiac events (cardiac deaths, re-infarction and new-onset heart failure) during in-hospital phase and follow-up period (366 days, inter-quartile range: 273-519 days). 215 consecutive ACS patients admitted to the coronary care unit (62.7±13.0 years, 24.2% female) were included. 47.4% had a diagnosis of ST segment elevation myocardial infarction. AGEs and sRAGE were analysed by fluorescence spectroscopy and competitive ELISA, respectively. Risk scores (GRACE, TIMI, PURSUIT) were calculated retrospectively using prospective data. The complexity of coronary artery disease was evaluated by SYNTAX score. RESULTS: The mean fluorescent AGEs and sRAGE levels were 57.7±45.1 AU and 1045.4±850.0 pg/mL, respectively. 19 patients presented cardiac events during in-hospital phase and 29 during the follow-up. In-hospital cardiac events were significantly associated with higher sRAGE levels (p = 0.001), but not long-term cardiac events (p = 0.365). Regarding fluorescent AGE the opposite happened. After multivariate analysis correcting by gender, left ventricular ejection fraction, glucose levels, haemoglobin, GRACE and SYNTAX scores, sRAGE was significantly associated with in-hospital prognosis, whereas fluorescent AGEs was significantly associated with long-term prognosis. CONCLUSIONS: We conclude that elevated values of sRAGE are associated with worse in-hospital prognosis, whereas high fluorescent AGE levels are associated with more follow-up events.

Statins modulate feedback regulation mechanisms between advanced glycation end-products and C-reactive protein: evidence in patients with acute myocardial infarction.

OBJECTIVE: High sensitivity C-reactive protein (hsCRP) and advanced glycation end-products (AGEs) have been proposed as mediators in inflammation and atherosclerosis. Therefore, we studied the relation between AGE and hsCRP in patients with acute myocardial infarction (AMI). METHODS: Patients with AMI diagnosis and satisfying our inclusion criteria were included during 2009-2011 in an unicentre registry of AMI patients for a cross-sectional study. The final cohort was composed of 156 patients (46.2% STEMI and 27.6% with type-2 diabetes). AGE and hsCRP were measured in plasma. RESULTS: Diabetic patients were older than non-diabetics (68.6 ± 10.6 vs. 60.4 ± 13.9 years; p<0.05), presented more incidence of hypertension (62.8 vs. 36.3%; p<0.05) and were in a higher Killip class (p<0.05). The mean values of fluorescent AGE and hsCRP levels were 61.3 ± 49.8 AU and 2.4 ± 4.0 mg/L, respectively, and there were no differences in these parameters between diabetic and non-diabetic patients. A direct association between AGE and hsCRP levels was observed, mainly in diabetic patients (r=0.258; p=0.018). Importantly, this association disappeared in patients who had been treated with statins before their AMI (r=-0.055; p=0.845), but it was maintained in non-diabetic patients naïve for statins treatment (r=0.634; p<0.001), independently of other treatments and confounding parameters. CONCLUSIONS: This is the first evidence in humans of a feedback regulation mechanism between CRP and the AGE-RAGE axis modulated by statins.