Clinical Characteristics and Prognostic Impact of Short Physical Performance Battery in Hospitalized Patients with Acute Heart Failure-Results of the PROFUND-IC Registry.

BACKGROUND: Most patients diagnosed with heart failure (HF) are older adults with multiple comorbidities. Multipathological patients constitute a population with common characteristics: greater clinical complexity and vulnerability, frailty, mortality, functional deterioration, polypharmacy, and poorer health-related quality of life with more dependency. OBJECTIVES: To evaluate the clinical characteristics of hospitalized patients with acute heart failure and to determine the prognosis of patients with acute heart failure according to the Short Physical Performance Battery (SPPB) scale. METHODS: Observational, prospective, and multicenter cohort study conducted from September 2020 to May 2022 in patients with acute heart failure as the main diagnosis and NT-ProBNP > 300 pg. The cohort included patients admitted to internal medicine departments in 18 hospitals in Spain. Epidemiological variables, comorbidities, cardiovascular risk factors, cardiovascular history, analytical parameters, and treatment during admission and discharge of the patients were collected. Level of frailty was assessed by the SPPB scale, and dependence, through the Barthel index. A descriptive analysis of all the variables was carried out, expressed as frequencies and percentages. A bivariate analysis of the SPPB was performed based on the score obtained (SPPB ≤ 5 and SPPB > 5). For the overall analysis of mortality, HF mortality, and readmission of patients at 30 days, 6 months, and 1 year, Kaplan-Meier survival curves were used, in which the survival experience among patients with an SPPB > 5 and SPPB ≤ 5 was compared. RESULTS: A total of 482 patients were divided into two groups according to the SPPB with a cut-off point of an SPPB < 5. In the sample, 349 patients (77.7%) had an SPPB ≤ 5 and 100 patients (22.30%) had an SPPB > 5. Females (61%) predominated in the group with an SPPB ≤ 5 and males (61%) in those with an SPPB > 5. The mean age was higher in patients with an SPPB ≤ 5 (85.63 years). Anemia was more frequent in patients with an SPPB ≤ 5 (39.5%) than in patients with an SPPB ≥ 5 (29%). This was also seen with osteoarthritis (32.7%, p = 0.000), diabetes (49.6%, p = 0.001), and dyslipidemia (69.6%, p = 0.011). Patients with an SPPB score > 5 had a Barthel index < 60 in only 4% (n = 4) of cases; the remainder of the patients (96%, n = 96) had a Barthel index > 60. Patients with an SPPB > 5 showed a higher probability of survival at 30 days (p = 0.029), 6 months (p = 0.031), and 1 year (p = 0.007) with (OR = 7.07; 95%CI (1.60-29.80); OR: 3.9; 95%CI (1.30-11.60); OR: 6.01; 95%CI (1.90-18.30)), respectively. No statistically significant differences were obtained in the probability of readmission at 30 days, 6 months, and 1 year (p > 0.05). CONCLUSIONS: Patients admitted with acute heart failure showed a high frequency of frailty as assessed by the SPPB. Patients with an SPPB ≤ 5 had greater comorbidities and greater functional limitations than patients with an SPPB > 5. Patients with heart failure and a Barthel index > 60 frequently presented an SPPB < 5. In daily clinical practice, priority should be given to performing the SPPB in patients with a Barthel index > 60 to assess frailty. Patients with an SPPB ≤ 5 had a higher risk of mortality at 30 days, 6 months, and 1 year than patients with an SPPB ≤ 5. The SPPB is a valid tool for identifying frailty in acute heart failure patients and predicting 30-day, 6-month, and 1-year mortality.

Effectiveness of the contingency plan for social and health care during the COVID-19 pandemic in a health district in northwestern Spain.

INTRODUCTION: During the COVID-19 pandemic, healthcare facilities have implemented contingency plans to minimize the consequences of this pathology however, the deployment and results of these contingency plans are scarcely shared. OBJECTIVES: To describe the implementation of the contingency plan in the social and health care in the COVID-19 pandemic in the Public Hospital of Monforte (Lugo, Spain) and to evaluate the effectiveness of the measures included in this plan. METHOD: Phenomenological sampling conducted between March 10 and May 15, 2020. Evaluation qualitative assessment by an external quality improvement team of the Galician Health Service (SERGAS), based on the Practicum Direct rapid structured checklist in risk management, organizational management, and evaluation of decision making. As outcome indicators, we assessed the number of hospital admissions, number of PCRs performed, telephone attention to social and health social-healthcare patients, number of hospitalizations avoided and estimation of their direct cost. RESULTS: After assessing and managing the risks, an information security plan was developed and solutions to minimize complications in our patients derived from this pandemic. An emergency decision making team was created, as well as an employee communication mechanism for employees through standardized documents and documentation channels. CONCLUSIONS: The adaptation of the Practicum Direct rapid model to the healthcare setting is a useful and easy-to-apply tool that allows us to identify weak points and areas for improvement in our Service and thus to strengthen patient care in all clinical areas, improving the quality of care.

Estimating the Prevalence of Cardiac Amyloidosis in Old Patients with Heart Failure-Barriers and Opportunities for Improvement: The PREVAMIC Study.

BACKGROUND: Cardiac amyloidosis (CA) could be a common cause of heart failure (HF). The objective of the study was to estimate the prevalence of CA in patients with HF. METHODS: Observational, prospective, and multicenter study involving 30 Spanish hospitals. A total of 453 patients ≥ 65 years with HF and an interventricular septum or posterior wall thickness > 12 mm were included. All patients underwent a 99mTc-DPD/PYP/HMDP scintigraphy and monoclonal bands were studied, following the current criteria for non-invasive diagnosis. In inconclusive cases, biopsies were performed. RESULTS: The vast majority of CA were diagnosed non-invasively. The prevalence was 20.1%. Most of the CA were transthyretin (ATTR-CM, 84.6%), with a minority of cardiac light-chain amyloidosis (AL-CM, 2.2%). The remaining (13.2%) was untyped. The prevalence was significantly higher in men (60.1% vs 39.9%, p = 0.019). Of the patients with CA, 26.5% had a left ventricular ejection fraction less than 50%. CONCLUSIONS: CA was the cause of HF in one out of five patients and should be screened in the elderly with HF and myocardial thickening, regardless of sex and LVEF. Few transthyretin-gene-sequencing studies were performed in older patients. In many patients, it was not possible to determine the amyloid subtype.

Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada / Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction

Antecedentes:El antígeno carbohidrato 125 (CA125) ha emergido como un nuevo biomarcador en insuficiencia cardiaca. El objetivo del estudio es determinar si los niveles séricos de CA125 predicen la mortalidad y reingresos totales a un año en pacientes mayores de 70 años e insuficiencia cardiaca aguda (ICA) con fracción de eyección preservada (FEP).Métodos:Estudio observacional prospectivo multicéntrico, que incluyó a 359 pacientes (edad media 81,5 años). La variable de valoración principal fue la mortalidad total por todas las causas y lo reingresos totales por ICA a un año. El análisis de regresión binomial negativa se utilizó para evaluar la asociación entre los valores de CA125 y el pronóstico.Resultados:Al año de seguimiento, se registraron 87 muertes (24,2%). Los pacientes del cuartil inferior de CA125 presentaron una tasa bruta de mortalidad menor (14,4%, 26,7, 26,7 y 29,2; p=0,090). Tras un análisis multivariado, el valor de CA125 se asoció de forma casi lineal y positiva a un mayor riesgo de mortalidad (p=0,009). Dicha asociación fue también positiva pero estadísticamente límite en el caso de los reingresos totales por ICA (p=0,089).Conclusiones:En población mayor de 70 años hospitalizada por ICA con FEP, los niveles elevados de CA125 se asocian a un aumento del riesgo de muerte a un año de seguimiento. La asociación con los reingresos fue más incierta. Los niveles bajos de CA125 identifica un subgrupo de pacientes de bajo riesgo. (AU)

Background:Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF).Methods:Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints.Results:At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089).Conclusions:In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk. (AU)

Ethnicity and Clinical Outcomes in Patients Hospitalized for COVID-19 in Spain: Results from the Multicenter SEMI-COVID-19 Registry.

(1) Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5−58.9) to 57.1 (44.1−67.1) vs. 71.5 (59.5−81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10−0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17−1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26−2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21−1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often.

Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry.

Uncontrolled inflammation following COVID-19 infection is an important characteristic of the most seriously ill patients. The present study aims to describe the clusters of inflammation in COVID-19 and to analyze their prognostic role. This is a retrospective observational study including 15,691 patients with a high degree of inflammation. They were included in the Spanish SEMI-COVID-19 registry from March 1, 2020 to May 1, 2021. The primary outcome was in-hospital mortality. Hierarchical cluster analysis identified 7 clusters. C1 is characterized by lymphopenia, C2 by elevated ferritin, and C3 by elevated LDH. C4 is characterized by lymphopenia plus elevated CRP and LDH and frequently also ferritin. C5 is defined by elevated CRP, and C6 by elevated ferritin and D-dimer, and frequently also elevated CRP and LDH. Finally, C7 is characterized by an elevated D-dimer. The clusters with the highest in-hospital mortality were C4, C6, and C7 (17.4% vs. 18% vs. 15.6% vs. 36.8% vs. 17.5% vs. 39.3% vs. 26.4%). Inflammation clusters were found as independent factors for in-hospital mortality. In detail and, having cluster C1 as reference, the model revealed a worse prognosis for all other clusters: C2 (OR = 1.30, p = 0.001), C3 (OR = 1.14, p = 0.178), C4 (OR = 2.28, p < 0.001), C5 (OR = 1.07, p = 0.479), C6 (OR = 2.29, p < 0.001), and C7 (OR = 1.28, p = 0.001). We identified 7 groups based on the presence of lymphopenia, elevated CRP, LDH, ferritin, and D-dimer at the time of hospital admission for COVID-19. Clusters C4 (lymphopenia + LDH + CRP), C6 (ferritin + D-dimer), and C7 (D-dimer) had the worst prognosis in terms of in-hospital mortality.

Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction. / Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada.

BACKGROUND: Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF). METHODS: Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints. RESULTS: At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089). CONCLUSIONS: In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk.

Impact of Arterial Stiffness on All-Cause Mortality in Patients Hospitalized With COVID-19 in Spain.

Older age and cardiovascular comorbidities are well-known risk factors for all-cause mortality in patients with coronavirus disease 2019 (COVID-19). Hypertension and age are the 2 principal determinants of arterial stiffness (AS). This study aimed to estimate AS in patients with COVID-19 requiring hospitalization and analyze its association with all-cause in-hospital mortality. This observational, retrospective, multicenter cohort study analyzed 12 170 patients admitted to 150 Spanish centers included in the SEMI-COVID-19 Network. We compared AS, defined as pulse pressure ≥60 mm Hg, and clinical characteristics between survivors and nonsurvivors. Mean age was 67.5 (±16.1) years and 42.5% were women. Overall, 2606 (21.4%) subjects died. Admission systolic blood pressure (BP) <120 and ≥140 mm Hg was a predictor of higher all-cause mortality (23.5% and 22.8%, respectively, P<0.001), compared with systolic BP between 120 and 140 mm Hg (18.6%). The 4379 patients with AS (36.0%) were older and had higher systolic and lower diastolic BP. Multivariate analysis showed that AS and systolic BP <120 mm Hg significantly and independently predicted all-cause in-hospital mortality (adjusted odds ratio [ORadj]: 1.27, P=0.0001; ORadj: 1.48, P=0.0001, respectively) after adjusting for sex (males, ORadj: 1.6, P=0.0001), age tertiles (second and third tertiles, ORadj: 2.0 and 4.7, P=0.0001), Charlson Comorbidity Index (second and third tertiles, ORadj: 4.8 and 8.6, P=0.0001), heart failure, and previous and in-hospital antihypertensive treatment. Our data show that AS and admission systolic BP <120 mm Hg had independent prognostic value for all-cause mortality in patients with COVID-19 requiring hospitalization.

COVID 19 comprehensive management in a regional hospital of Northwestern Spain.

INTRODUCTION: The COVID-19 pandemic has brought about a paradigm shift in healthcare. OBJECTIVE: To evaluate the utility of a strategy to comprehensively address the pandemic in a health area that covers 42,000 people. METHOD: Between March 10 and May 15, 2020, the COVID Unit was created in the corresponding regional hospital, and an independent circuit was established for the diagnosis and management of patients with suspected or confirmed COVID-19; social health centers were monitored with PCR testing. RESULTS: Eighteen COVID-19-positive patients (age 72.9 ± 13.2 years) were admitted, out of which 66% were males. All these patients had pneumonia and 67% had respiratory distress syndrome; no one required mechanical ventilation. Mean hospital stay was 9.4 ± 5.3 days, and mortality, 11%. PCR tests were applied to all hospital residents (n = 827) and workers (n = 519), 1,044 phone calls were made and 36 hospital admissions were avoided. Only 50 patients required close follow-up, out of which four (0.48%) were positive for COVID-19. CONCLUSION: Clinical monitoring at the hospital and social health centers showed that patient profile was like that documented in the literature and that the incidence of COVID-19 was low in social health centers.

INTRODUCCIÓN: La pandemia de COVID-19 provocó un cambio de paradigma en la atención médica. OBJETIVO: Evaluar una estrategia para abordar integralmente la pandemia en un distrito de salud que comprende 42 000 personas. MÉTODO: Entre el 10 de marzo y 15 de mayo de 2020 se creó la Unidad COVID en un hospital regional correspondiente al distrito y se estableció un circuito independiente para el diagnóstico y manejo de pacientes con sospecha o confirmación de COVID-19; los centros de salud social fueron monitoreados mediante PCR. RESULTADOS: Ingresaron 18 pacientes positivos a COVID-19 (edad de 72.9 ± 13.2 años), 66 % eran hombres; todos presentaron neumonía, 67 % desarrolló síndrome de dificultad respiratoria y ninguno requirió ventilación mecánica. La estancia hospitalaria fue de 9.4 ± 5.3 días y la mortalidad, de 11 %. Se realizaron pruebas de PCR a todos los residentes (n = 827) y trabajadores (n = 519) del hospital, se realizaron 1044 llamadas telefónicas y se evitaron 36 hospitalizaciones. Solo 50 pacientes necesitaron seguimiento cercano, cuatro (0.48 %) positivos a COVID-19. CONCLUSIÓN: El monitoreo clínico en el hospital y centros de salud social mostró que el perfil de los pacientes fue similar al documentado en la literatura y que la incidencia de COVID-19 fue baja en los centros sociales de salud.

COVID 19 comprehensive management in a regional hospital of Northwestern Spain / Gestión integral de COVID 19 en un hospital regional en el noroeste de España

Abstract Introduction: The COVID-19 pandemic has brought about a paradigm shift in healthcare. Objective: To evaluate the utility of a strategy to comprehensively address the pandemic in a health area that covers 42,000 people. Method: Between March 10 and May 15, 2020, the COVID Unit was created in the corresponding regional hospital, and an independent circuit was established for the diagnosis and management of patients with suspected or confirmed COVID-19; social health centers were monitored with PCR testing. Results: Eighteen COVID-19-positive patients (age 72.9 ± 13.2 years) were admitted, out of which 66% were males. All these patients had pneumonia and 67% had respiratory distress syndrome; no one required mechanical ventilation. Mean hospital stay was 9.4 ± 5.3 days, and mortality, 11%. PCR tests were applied to all hospital residents (n = 827) and workers (n = 519), 1,044 phone calls were made and 36 hospital admissions were avoided. Only 50 patients required close follow-up, out of which four (0.48%) were positive for COVID-19. Conclusion: Clinical monitoring at the hospital and social health centers showed that patient profile was like that documented in the literature and that the incidence of COVID-19 was low in social health centers.

Resumen Introducción: La pandemia de COVID-19 provocó un cambio de paradigma en la atención médica. Objetivo: Evaluar una estrategia para abordar integralmente la pandemia en un distrito de salud que comprende 42 000 personas. Método: Entre el 10 de marzo y 15 de mayo de 2020 se creó la Unidad COVID en un hospital regional correspondiente al distrito y se estableció un circuito independiente para el diagnóstico y manejo de pacientes con sospecha o confirmación de COVID-19; los centros de salud social fueron monitoreados mediante PCR. Resultados: Ingresaron 18 pacientes positivos a COVID-19 (edad de 72.9 ± 13.2 años), 66 % eran hombres; todos presentaron neumonía, 67 % desarrolló síndrome de dificultad respiratoria y ninguno requirió ventilación mecánica. La estancia hospitalaria fue de 9.4 ± 5.3 días y la mortalidad, de 11 %. Se realizaron pruebas de PCR a todos los residentes (n = 827) y trabajadores (n = 519) del hospital, se realizaron 1044 llamadas telefónicas y se evitaron 36 hospitalizaciones. Solo 50 pacientes necesitaron seguimiento cercano, cuatro (0.48 %) positivos a COVID-19. Conclusión: El monitoreo clínico en el hospital y centros de salud social mostró que el perfil de los pacientes fue similar al documentado en la literatura y que la incidencia de COVID-19 fue baja en los centros sociales de salud.

Usefulness of carotid ultrasonography in the assessment of coronary artery disease extension in patients undergoing exercise echocardiography.

OBJECTIVES: To evaluate whether carotid disease is associated with coronary artery disease (CAD) extension in patients undergoing treadmill exercise stress echocardiography (EE). METHODS: We retrospectively studied 156 patients without previous vascular disease who underwent EE, carotid ultrasonography, and coronary angiography between 2002 and 2013. Low-, intermediate-, and high-risk EE were defined as negative, localized ischemia, and multivessel/extensive ischemia EE respectively; carotid disease according to Mannheim and American Society of Echocardiography Consensus and CAD extension from zero to three vessel disease as stenosis ≥50% by visual assessment. RESULTS: Of the 156 patients, 67 (42.9%), 43 (27.6%), 22 (14.1%), and 24 (15.4%) had zero, one, two, and three vessel disease respectively. Age (P = 0.047), male sex (P = 0.010), diabetes mellitus (P = 0.039), smoking habit (P = 0.015), fasting plasma glucose (P = 0.021), European Systematic COronary Risk Evaluation (P = 0.003), pretest CAD probability (P = 0.003), high-risk EE (P < 0.001), and carotid plaque presence (CP) (P < 0.001) were associated in univariate analysis with more extensive CAD. Predictors of CAD extension in multivariate analysis were high-risk EE (odds ratio [OR] 2.42, P < 0.001), CP presence (OR 1.75, P = 0.004), and pretest CAD probability >65% (OR 1.49, P = 0.023). CP was also associated with multivessel CAD in the 53 patients with low- or intermediate-risk EE (P = 0.001). CONCLUSIONS: CP is associated with CAD extension in patients with ischemic heart disease suspicion undergoing EE. Patients with CP could benefit from a more aggressive therapeutic strategy regarding patients without carotid disease and similar risk EE, especially in intermediate- and/or low-risk test where guidelines recommend initially optimal medical treatment.

Usefulness of carotid ultrasonography in the diagnosis of coronary artery disease in patients undergoing exercise echocardiography.

BACKGROUND: Relationship between carotid and coronary artery disease (CAD) in patients undergoing invasive and non-invasive test is unclear. The aim of the study is to evaluate whether carotid disease is associated with CAD in patients submitted to exercise echocardiography (EE) and if it improves the EE ability to predict CAD. METHODS: We retrospectively studied 156 subjects without previous vascular disease who underwent EE, carotid ultrasonography and coronary angiography between 2002 and 2013. Positive EE was defined as exercise induced wall motion abnormalities, carotid disease according to Manheim and American Society of Echocardiography Consensus and significant CAD as stenosis ≥50%. RESULTS: Eighty-nine (57.1%) subjects had significant CAD. Factors associated with CAD in multivariate analysis were fasting plasma glucose (odds ratio [OR] 1.02, p = 0.031), pre-test probability of CAD > 65% (OR 3.71, p < 0.001), positive EE (OR 10.51, p < 0.001) and carotid plaque (CP) presence (OR 2.95, p = 0.013). There was neither statistical significant difference in area under the curve after addition of CP to EE results (0.77 versus 0.81, p = 0.525) nor sensitivity, specificity, predictive values or efficiency. CP presence reclassified as very high-risk according to Systematic COronary Risk Evaluation 13 patients (34.2%) with negative EE and 22 (33.3%) without CAD. CONCLUSION: CP is associated with CAD in patients undergoing EE, however its addition to EE does not improve CAD prediction, probably due to insufficient statistical power. CP reclassified one third of patients to very high-risk category despite negative EE or CAD absence, these subjects benefit from aggressive primary prevention interventions.