Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors.

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.

Early ischemia identification employing 2D speckle tracking selective layers analysis during dobutamine stress echocardiography.

PURPOSE: Two-dimensional (2D) strain derived from speckle tracking proved to be feasible and accurate in the quantitative evaluation of myocardial ischemia during stress echocardiography. We compared the accuracy in detecting myocardial ischemia of the transmural segmental analysis with an endocardial specific evaluation in 20 patients undergoing dobutamine stress echocardiography (DSE) and coronary angiography. METHODS: Peak systolic global strain (G-ε) and at the subendocardial level (Endo-ε) were measured off-line at rest, a low dose, and peak stress; then, we compared the results with wall-motion analysis and significant coronary artery disease (CAD > 70% diameter stenosis). Endocardial strain variation from basal to low and peak dose was computed both for global or subendocardial analysis. The utilization of the ROC curve allowed us to derive optimal cutoffs, sensibility and specificity for ischemic segments. RESULTS: The subendocardial analysis at high dose showed to be able to increase significantly the accuracy of the test to detect the ischemic segments (sens 90.2% vs 85.4%; spec 93.1% vs 92.2%). Moreover, at the low dose, the subendocardial analysis showed to be able to increase significantly, mostly the specificity of the test (sens 69.6% vs 68.3%; spec 92.2% vs 86.2%). Notably, the strain subendocardial analysis at low dose showed to reach a high specificity, similar to the peak dose transmural analysis. CONCLUSIONS: Measurement of subendocardial strain during DSE is feasible and can increase the accuracy of the test. Moreover, the subendocardial strain during DSE can reach a high specificity, even limiting the test at a low dose infusion.

Metabolomic Perspectives in Antiblastic Cardiotoxicity and Cardioprotection.

Despite advances in supportive and protective therapy for myocardial function, cardiovascular diseases due to antineoplastic therapy-primarily cardiomyopathy associated with contractile dysfunction-remain a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators are searching for alternative strategies that can timely recognise cardiovascular damage-thus permitting a quick therapeutic approach-or prevent the development of the disease. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as tyrosine kinase inhibitors. In recent years, metabolomics has proved to be a practical tool to highlight fundamental changes in the metabolic state in several pathological conditions. In this article, we present the state-of-the-art technology with regard to the metabolic mechanisms underlying cardiotoxicity and cardioprotection.

Potential cardiac risk of immune-checkpoint blockade as anticancer treatment: What we know, what we do not know, and what we can do to prevent adverse effects.

Cancer immunotherapy has become a well-established treatment option for some cancers after the development of a family of drugs targeting the so-called immune checkpoints, such as CTLA4 and PD-1 with PD-L1. These co-receptors/ligands inhibit the activation of T-cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint-blocking drugs is to awake an immune response primarily directed against cancer cells. Nonetheless, as the immune response elicited by these drugs is not completely tumor-specific, their use may actually cause several adverse effects, including adverse cardiovascular effects. In this review, we will discuss the principles and potentiality of immunotherapy for cancer treatment, the experimental and clinical data on the role of CTLA4 and PD-1 with PD-L1 as immune-checkpoints in the cancer environment and in the cardiovascular system, and strategies aimed at preventing possible cardiovascular adverse effects of immune-checkpoint blockers.

Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease.

BACKGROUND: The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded as an integrated index of individual atherogenic and anti-atherogenic properties, and that the interaction between circulating factors and the arterial wall might be critical for atherogenesis. In organism-level investigations, a functional view is provided by metabolomics, the study of the metabolic profile of small molecules. We sought to verify whether metabolomic analysis can reveal the presence of coronary microenvironment peculiarities associated with distinct manifestations of CAD. METHODS: Thirty-two coronary blood samples were analyzed using 1H-NMR-based metabolomics. Samples collected from patients with evidence of myocardial ischemia formed the case group, and were further divided into the stenotic-disease (SD) group (N = 13) and absence of stenosis (microvascular disease; "Micro") group (N = 8); specimens of patients presenting no evidence of ischemic heart disease (dilated cardiomyopathy, valvular diseases) constituted the control group (N = 11). RESULTS: Application of an orthogonal partial least squares discriminant analysis (OPLS-DA) model to the entire dataset clearly separated the samples into 3 groups, indicating 3 distinct metabolic fingerprints. Relative to control-group members, Micro patients showed a higher content of 2-hydroxybutirate, alanine, leucine, isoleucine, and N-acetyl groups and lower levels of creatine/phosphocreatine, creatinine, and glucose, whereas SD patients showed higher levels of 3-hydroxybutirate and acetate and a lower content of 2-hydroxybutirate. Moreover, relative to SD patients, Micro patients showed higher levels of 2-hydroxybutirate, alanine, leucine, and N-acetyl groups and lower levels of 3-hydroxybutirate and acetate. CONCLUSIONS: Specific coronary microenvironments are likely associated with distinct development and pathological expression of CAD.

Metabolomic approach to profile functional and metabolic changes in heart failure.

BACKGROUND: Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. METHODS: A 500 MHz proton nuclear magnetic resonance ((1)H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 ± 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 ± 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. RESULTS: OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R(2) [R(2)(X) = 0.64; R(2)(Y) = 0.59] and Q(2) (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. CONCLUSIONS: The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function.

Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection.

Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies.

Heart rate variability shows different cardiovascular modulation in Parkinson's disease patients with tremor dominant subtype compared to those with akinetic rigid dominant subtype.

Parkinson's disease (PD) can present with different motor subtypes depending on the predominant symptoms (tremor or rigidity/bradykinesia). Slower disease progression and less cognitive decline are observed in tremor-dominant patients compared to those with akinetic-rigid subtype. Autonomic cardiovascular disorders have been described in parkinsonian patients, although the definite correlations with different subtypes of PD are not clear. In this context, heart rate variability (HRV) analysis represents a non-invasive and established tool in assessing cardiovascular autonomic modulation. We investigate cardiovascular autonomic modulation in PD patients with tremor dominant subtype in comparison to akinetic rigid dominant subtype subjects using HRV analysis. Twenty-eight PD patients (17 with tremor dominant subtype and 11 with akinetic rigid dominant subtype) were enrolled and compared to 17 age and sex-matched healthy controls. HRV was analyzed in time- and frequency-domains. Low-frequency (LF) values were significantly lower in the akinetic rigid dominant subtype than in the tremor dominant group [LF 41.4 ± 13.6 vs 55.5 ± 11.6 (p < 0.007)] indicating that the disease led to a more evident impairment of the baroreflex modulation of the autonomic outflow mediated by both sympathetic and parasympathetic systems in the first class of patients. These findings support the biological relevance of clinical subtypes supporting the idea of a different pathophysiological process between these subtypes. These differences also suggest that different subtypes may also result in different responses to therapy or in the possible development of cardiovascular side effects of dopaminergic drugs in these different populations.

Effects of metformin and exercise training, alone or in association, on cardio-pulmonary performance and quality of life in insulin resistance patients.

BACKGROUND: Metformin (MET) therapy exerts positive effects improving glucose tolerance and preventing the evolution toward diabetes in insulin resistant patients. It has been shown that adding MET to exercise training does not improve insulin sensitivity. The aim of this study was to determine the effect of MET and exercise training alone or in combination on maximal aerobic capacity and, as a secondary end-point on quality of life indexes in individuals with insulin resistance. METHODS: 75 insulin resistant patients were enrolled and subsequently assigned to MET (M), MET with exercise training (MEx), and exercise training alone (Ex). 12-weeks of supervised exercise-training program was carried out in both Ex and MEx groups. Cardiopulmonary exercise test and SF-36 to evaluate Health-Related Quality of Life (HRQoL) was performed at basal and after 12-weeks of treatment. RESULTS: Cardiopulmonary exercise test showed a significant increase of peak VO2 in Ex and MEx whereas M showed no improvement of peak VO2 (∆ VO2 [CI 95%] Ex +0.26 [0.47 to 0.05] l/min; ∆ VO2 MEx +0.19 [0.33 to 0.05] l/min; ∆ VO2 M -0.09 [-0.03 to -0.15] l/min; M vs E p < 0.01; M vs MEx p < 0.01; MEx vs Ex p = ns). SF-36 highlighted a significant increase in general QoL index in the MEx (58.3 ± 19 vs 77.3 ± 16; p < 0.01) and Ex (62.1 ± 17 vs 73.7 ± 12; p < 0.005) groups. CONCLUSIONS: We evidenced that cardiopulmonary negative effects showed by MET therapy may be counterbalanced with the combination of exercise training. Given that exercise training associated with MET produced similar effects to exercise training alone in terms of maximal aerobic capacity and HRQoL, programmed exercise training remains the first choice therapy in insulin resistant patients.

Ankle-brachial index and its link to automated carotid ultrasound measurement of intima-media thickness variability in 500 Japanese coronary artery disease patients.

The purpose of this study was to evaluate whether the carotid intima-media thickness (cIMT) and intima-media thickness variability (IMTV) along the artery are correlated to the ankle-brachial index (ABI) in Japanese coronary artery disease patients. Five hundred consecutive patients (312 males; median age 69 ± 11 years) who underwent carotid ultrasonography and first coronary angiography were prospectively analyzed. By using automated software (AtheroEdge™, AtheroPoint, Roseville, CA, USA), we obtained the cIMT and IMTV. Pearson correlation analysis was performed to calculate the association between ABI, automatically measured cIMT, automatically measured IMTV, and the SYNTAX score. The mean cIMT was 0.881 ± 0.334 mm and the mean IMTV was 0.141 ± 0.112. IMTV was negatively and significantly correlated to ABI (ρ = -0.147; p = 0.001), whereas cIMT was not (ρ = -0.075; p = 0.097). IMTV and cIMT had the same significant correlation with the SYNTAX score. When we considered patients with a higher risk factor (ABI ≤ 0.9), we found higher values of IMTV and the SYNTAX score, but not higher values of cIMT. Logistic regression analysis showed that IMTV was independently associated with the complexity of the coronary artery disease (as assessed by the SYNTAX score). In conclusion, we show that IMTV automatically measured using AtheroEdge™ was correlated with ABI, whereas cIMT was not. IMTV could be integrated with cIMT measurement to improve the assessment of cardiovascular disease.

Gender Effect on Clinical Profiles, Pharmacological Treatments and Prognosis in Patients Hospitalized for Heart Failure.

Heart failure (HF) is a significant disease affecting 1-2% of the general population. Despite its general aspects, HF, like other cardiovascular diseases, presents various gender-specific aspects in terms of etiology, hemodynamics, clinical characteristics, therapy, and outcomes. As is well known, HF with preserved ejection fraction more frequently affects females, with diabetes and arterial hypertension representing the most critical determinants of HF. On the other hand, women are traditionally underrepresented in clinical trials and are often considered undertreated. However, it is not clear whether such differences reflect cultural behaviors and clinical inertia or if they indicate different clinical profiles and the impact of sex on hard clinical outcomes. We aimed to review the sex-related differences in patients affected by HF.

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this affects cardiovascular and tumor biomarkers; exploring the role of cardiovascular biomarkers in the risk stratification and in the identification of chemotherapy-induced cardiotoxicity; and providing a summary of the novel potential biomarkers in this clinical setting.

Management of cancer patients at high and very-high risk of cardiotoxicity: Main questions and answers.

In recent years, important advances have been made in the field of Cardio-Oncology. The 2022 ESC Guidelines on Cardio-Oncology proposed a baseline cardiovascular risk stratification for cancer patients and preventive strategies in patients at high and very-high risk of cardiotoxicity. Cardiovascular toxic effects of anti-cancer drugs are being extensively studied; surveillance programs have been proposed, based on the baseline cardiovascular risk. On the other hand, there is little data on Cardio-Oncological management of patients at high and very-high cardiovascular risk with previous cardiovascular diseases. For example, little is known about management of cancer patients with heart failure with reduced ejection fraction (HFrEF), patients with a recent myocardial infarction or other cardiovascular diseases; when to resume anti-cancer drugs after a cardiovascular toxic event. Collaboration between Cardiologists and Oncologists and multidisciplinary team evaluations are certainly essential to decide the best therapeutic strategy for cancer patients, to treat cancer while saving the heart. Therefore, in the present review, we attempt to provide a useful guide to clinicians in treating patients with high and very-high risk of cardiotoxicity by enucleating main questions and answering them based on the evidence available as well as expert opinion and our clinical experience.

Early impairment of contractility reserve in patients with insulin resistance in comparison with healthy subjects.

BACKGROUND: Insulin resistance (IR) is currently considered a crucial cardiovascular (CV) risk factor, which seems to play a dominant role in the evolution toward cardiac and vascular impairment. Early IR-induced cardiac dysfunction can be assessed by Doppler-derived myocardial systolic strain rate (SR) index, measured at baseline and after dobutamine stress echocardiography (DSE). METHODS: Thirty IR patients (HOMA-IR = 7 ± 5.2, age 52.6 ± 2.1 years), and 20 healthy, age and sex matched controls were studied. IR had been diagnosed in all patients in the 3 months preceding the study. Dobutamine echocardiography was performed in all subjects to exclude ischemic heart disease, and left ventricular contractile reserve (LVCR) was then assessed. LVCR was evaluated as an increase in the peak of an average longitudinal SR, measured in the basal and mid segments of 2 and 4 chamber ventricular walls. RESULTS: No significant differences between the 2 groups were revealed by baseline echocardiography. In contrast, after DSE a significant decrease of Delta SR was found in the IR group in comparison to the controls (0.54 ± 0.31 s⁻¹ vs 1.14 ± 0.45 s⁻¹; p < 0.0001). CONCLUSIONS: Our results show that IR, even if isolated and arising within a short time period, not only represents the initial phase of future diabetes, but may adversely affect heart function, as evidenced by the depressed LVCR. Our data strengthen the need for attention to be paid to IR state and for an early therapeutic approach.

Right Ventricular Subclinical Dysfunction in SLE Patients Correlates with Metabolomic Fingerprint and Organ Damage.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, and several studies have suggested possible early RV involvement. Aim of the study was to evaluate the 3D echo parameters of the right ventricle (RV) and the metabolomic profile to correlate both with SLE severity. Forty SLE patients, free of cardiovascular disease, were enrolled and the following 3D parameters were evaluated: the RV ejection fraction (RV-EF), longitudinal strain of the interventricular septum (Septal LS), longitudinal strain of the free wall (Free-LS) and the fractional area change (FAC). In addition, a metabolomic analysis was performed. Direct correlations were observed between TAPSE values and the RV 3D parameters. Then, when splitting the population according to the SDI value, it was found that patients with higher cumulative damage (≥3) had significantly lower FAC, RV-EF, Septal LS, and Free-LS values; the latter three parameters showed a significant correlation with the metabolic profile of the patients. Furthermore, the division based on SDI values identified different metabolic profiles related to the degree of RV dysfunction. The RV dysfunction induced by the chronic inflammatory state present in SLE can be identified early by 3D echocardiography. Its severity seems to be related to systemic organ damage and the results associated with a specific metabolic fingerprint constituted by 2,4-dihydroxybutyric acid, 3,4-dihydroxybutyric acid, citric acid, glucose, glutamine, glycine, linoleic acid, oleic acid, phosphate, urea, and valine.

Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on 'gender cardiovascular diseases'.

The coronavirus disease 19 (COVID-19), due to coronavirus 2 (SARS-CoV-2) infection, presents with an extremely heterogeneous spectrum of symptoms and signs. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality than women. In particular, cardiovascular diseases (preexistent or arising upon infection) play a central role in COVID-19 outcomes, differently in men and women. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Such variability can be ascribed to both sex-related biological factors and sex-related behavioural traits. Sex differences in cardiovascular disease and COVID-19 involve the endothelial dysfunction, the innate immune system and the renin-angiotensin system (RAS). Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19 and it shows hormone-dependent actions. The incidence of myocardial injury during COVID-19 is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders among men. Its pathogenesis is not fully elucidated, but the main theories foresee a direct role for the ACE2 receptor, the hyperimmune response and the RAS imbalance, which may also lead to isolated presentation of COVID-19-mediated myopericarditis. Moreover, the latest evidence on cardiovascular diseases and their relationship with COVID-19 during pregnancy will be discussed. Finally, authors will analyse the prevalence of the long-covid syndrome between the two sexes and its impact on the quality of life and cardiovascular health.

Could CMR Tissue-Tracking and Parametric Mapping Distinguish Between Takotsubo Syndrome and Acute Myocarditis? A Pilot Study.

RATIONALE AND OBJECTIVE: Takotsubo syndrome (TS) is a transient and often misdiagnosed form of left ventricular dysfunction. Acute myocarditis (AM) is usually included in TS differential diagnosis. The aim of this study is to assess the role of cardiac magnetic resonance imaging coupled with tissue-tracking technique (CMR-TT) and parametric mappings analysis in discriminating between TS and AM. MATERIALS AND METHODS: We retrospectively enrolled three groups: patients with TS (n = 12), patients with AM (n = 14), and 10 healthy controls. All the patients had a comprehensive CMR examination, including the assessment of global and segmental longitudinal strain, circumferential strain, radial strain (RS), and parametric mapping. RESULTS: The analysis of variance was used to compare the different groups. In TS patients, basal RS, global T1 mapping, global T2 mapping, mid T2 mapping, apical T1 and T2 mapping were statistically significantly different compared with the other groups. MANCOVA analysis confirmed that the association between myocardial strain data and parametric mapping was independent on age and sex. Apical T1 and T2 mapping proved to have a good performance in differentiating TS from AM (area under the curves of 0.908 and 0.879, respectively). CONCLUSION: Basal RS and apical tissue mapping analysis are the most advanced CMR-derived parameters in making a differential diagnosis between TS and AM.

Metabolomic Profiles on Antiblastic Cardiotoxicity: New Perspectives for Early Diagnosis and Cardioprotection.

Antiblastic drugs-induced cardiomyopathy remains a relevant cause of morbidity and mortality, during and after chemotherapy, despite the progression in protective therapy against cardiovascular diseases and myocardial function. In the last few decades, many groups of researchers have focused their attention on studying the metabolic profile, first in animals, and, subsequently, in humans, looking for profiles which could be able to predict drug-induced cardiotoxicity and cardiovascular damage. In clinical practice, patients identified as being at risk of developing cardiotoxicity undergo a close follow-up and more tailored therapies. Injury to the heart can be a consequence of both new targeted therapies, such as tyrosine kinase inhibitors, and conventional chemotherapeutic agents, such as anthracyclines. This review aims to describe all of the studies carried on this topic of growing interest.

[Appropriateness of the request for preoperative cardiological evaluation in non-cardiac surgery: 8-year experience in a high-volume cardiological center]. / Appropriatezza della richiesta di consulenza cardiologica preoperatoria nella chirurgia non cardiaca: esperienza di 8 anni di un centro cardiologico ad alto volume di attività.

BACKGROUND: In the last decades the population undergoing non-cardiac surgery has become more numerous and complex. Cardiovascular perioperative complications represent at least one third of the perioperative deaths. Despite the pivotal role of the cardiologist in the perioperative management, current guidelines are often hardly useful in different settings of clinical practice. Local clinical protocols contribute to fill these gaps, to define the role of each specialist in the perioperative context and to achieve the best medical outcome. METHODS: This single-center retrospective study analyzes the background of 33 463 preoperatory cardiologic visits, the adherence to scientific evidence in our institute and the impact of the implementation of a shared clinical protocol (CP) in terms of reduction of inappropriate requests of cardiological evaluations. RESULTS: Among all the patients, the mean age was 59 ± 18 years, 52.8% were male. Hypertension was the most prevalent disease followed by diabetes, chronic coronary syndrome and atrial fibrillation. The "low-risk surgery" category was the most represented (56.2%) and the vast majority of patients (70.1%) was totally free from predictors of perioperative cardiovascular events. After the introduction of the CP, the number of inappropriate evaluations decreased by 32%, mainly in the low-risk category. However, despite the overall reduction, almost two thirds of the evaluations were still deemed inappropriate according to the CP, mostly (82.9%) in the low-risk category and to a lesser degree (55%) in the moderate/high-risk category. CONCLUSIONS: The inappropriate use of the resources resulted in disappointing organizational performance, poor assistance quality and a huge number of inappropriate preoperatory evaluations. The implementation of a CP, developed on the basis of the local needs, is a useful tool to enhance the organizational standards for the cardiological evaluation of patients undergoing non-cardiac surgery. Regular verifications, a widespread knowledge of the guidelines and a more efficient system of management and surveillance may improve the appropriateness of these evaluations.

Why Do High-Risk Patients Develop or Not Develop Coronary Artery Disease? Metabolic Insights from the CAPIRE Study.

Traditional cardiovascular (CV) risk factors (RFs) and coronary artery disease (CAD) do not always show a direct correlation. We investigated the metabolic differences in a cohort of patients with a high CV risk profile who developed, or did not develop, among those enrolled in the Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation (CAPIRE) study. We studied 112 subjects with a high CV risk profile, subdividing them according to the presence (CAD/High-RFs) or absence of CAD (No-CAD/High-RFs), assessed by computed tomography angiography. The metabolic differences between the two groups were identified by gas chromatography-mass spectrometry. Characteristic patterns and specific metabolites emerged for each of the two phenotypic groups: high concentrations of pyruvic acid, pipecolic acid, p-cresol, 3-aminoisobutyric acid, isoleucine, glyceric acid, lactic acid, sucrose, phosphoric acid, trimethylamine-N-oxide, 3-hydroxy-3-methylglutaric acid, erythritol, 3-hydroxybutyric acid, glucose, leucine, and glutamic acid; and low concentrations of cholesterol, hypoxanthine, glycerol-3-P, and cysteine in the CAD/High-RFs group vs the No-CAD/High-RFs group. Our results show the existence of different metabolic profiles between patients who develop CAD and those who do not, despite comparable high CV risk profiles. A specific cluster of metabolites, rather than a single marker, appears to be able to identify novel predisposing or protective mechanisms towards CAD beyond classic CVRFs.