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1.
Arch Cardiol Mex ; 2024 Jul 26.
Article in Spanish | MEDLINE | ID: mdl-39058955

ABSTRACT

Objective: SARS-CoV-2 infection induces an immune response that causes excessive inflammation damaging cardiac tissue and vascular endothelium. The objective of this study is to review a series of cases of hospitalized patients with pre-existing cardiac disease to describe the clinical behavior and highlight the low frequency of morbidity and mortality. Method: Retrospective study of 17 patients with a confirmed diagnosis of COVID-19 by polymerase chain reaction test or antigen test, a history of cardiovascular disease with or without comorbidities, and a history of at least one dose of the vaccine for COVID-19, during the period between December 30, 2021 and March 17, 2022 at the Ignacio Chávez National Institute of Cardiology in Mexico City. Results: The most frequent cardiac pathology was acute myocardial infarction (31.25%) and the most common arrhythmia was atrial fibrillation (25%). The median number of days of hospital stay was 10 days (interquartile range: 4-14). Regarding the outcomes, 94% of the patients were discharged due to clinical improvement, and only one patient died during his hospitalization. Conclusions: It is crucial to continue investigating SARS-CoV-2 effects in patients pre-existing heart disease and in those with persistent symptoms after infection. This will allow the development of more effective strategies for the treatment and prevention of cardiovascular complications associated with COVID-19.


Objetivo: La infección por SARS-CoV-2 induce una respuesta inmunitaria que causa una inflamación excesiva dañando al tejido cardiaco y al endotelio vascular. El objetivo de este estudio es revisar una serie de casos de pacientes hospitalizados con patología cardiaca preexistente para describir el comportamiento clínico y resaltar la baja frecuencia de morbimortalidad. Método: Estudio retrospectivo de 17 pacientes con diagnóstico confirmado de COVID-19 mediante prueba de reacción en cadena de la polimerasa o prueba de antígenos, antecedente de enfermedad cardiovascular en presencia o no de comorbilidad, y antecedente de al menos una dosis de la vacuna para la COVID-19, durante el periodo entre el 30 de diciembre de 2021 y el 17 de marzo de 2022, en el Instituto Nacional de Cardiología Ignacio Chávez de la Ciudad de México. Resultados: La patología cardiaca previa más frecuente fue el infarto agudo de miocardio (31.25%), y la arritmia más común fue la fibrilación auricular (25%). La mediana de días de estancia hospitalaria fue de 10 (rango intercuartílico: 4-14). En cuanto a los desenlaces, el 94% de los pacientes fueron dados de alta por mejoría clínica y solo un paciente falleció durante su internamiento. Conclusiones: Es crucial continuar investigando y monitoreando los efectos del SARS-CoV-2 en los pacientes con enfermedades cardiacas preexistentes y en aquellos con síntomas persistentes después de la infección. Esto permitirá desarrollar estrategias más efectivas para el tratamiento y la prevención de las complicaciones cardiovasculares asociadas a la COVID-19.

2.
Arch Cardiol Mex ; 94(1): 79-85, 2024.
Article in English | MEDLINE | ID: mdl-38507324

ABSTRACT

BACKGROUND: In Mexico, the epidemiology of heart failure is still not well understood. However, it is known that the primary cause of hospital admissions in patients with heart failure is pulmonary and systemic congestion. OBJECTIVE: To estimate congestion status and assess cardiac function using portable ultrasound in patients with heart failure. METHOD: A cross-sectional observational study was conducted. Patients who attended the Heart Failure Clinic at the Ignacio Chávez National Cardiology Institute in Mexico City between May and August 2022 were selected. They underwent ultrasonographic evaluation using a portable device to assess pulmonary and systemic congestion, as well as cardiac function and structure. RESULTS: One-hundred patients diagnosed with heart failure were prospectively included during the study period; 76% were male, with an average age of 59 years (range: 50-68 years). The recorded LVEF median was 34% (IQR: 27-43.5%). When evaluating pulmonary congestion, 78% of the patients showed a pattern A and 22% a pattern B. Following the VExUS protocol, 92% of the patients were at grade 0, 2% at grade 1, and 6% at grade 2. CONCLUSIONS: The use of the portable ultrasound facilitated the quantitative characterization of the echocardiographic features of the studied population. This device could provide better clinical characterization which, in turn, might allow for optimized drug prescription for heart failure and dose adjustments of diuretics based on echocardiographic congestion findings.


ANTECEDENTES: En México aún es muy poco conocida la epidemiología de la insuficiencia cardiaca, sin embargo se sabe que la principal causa de ingresos hospitalarios en los pacientes con insuficiencia cardiaca es la congestión pulmonar y sistémica. OBJETIVO: Estimar el estado de congestión y evaluar la función cardiaca mediante el ultrasonido portátil en pacientes con insuficiencia cardiaca tratados en un centro de tercer nivel en México. MÉTODO: Se llevó a cabo un estudio observacional transversal. Se seleccionaron pacientes que acudieron a la Clínica de Insuficiencia Cardiaca del Instituto Nacional de Cardiología Ignacio Chávez en la Ciudad de México entre mayo y agosto de 2022. Se les sometió a una evaluación ultrasonográfica mediante un dispositivo portátil para valorar la congestión pulmonar y sistémica, así como la función y estructura cardiaca. RESULTADOS: Se incluyeron de forma prospectiva 100 pacientes diagnosticados con insuficiencia cardiaca en el periodo de estudio. El 76% fueron hombres, con una edad mediana de 59 años (RIQ: 50-68 años). La mediana del FEVI registrada fue del 34% (RIQ: 27.0-43.5%). Al evaluar la congestión pulmonar, el 78% de los pacientes presentaron un patrón A y el 22% un patrón B. Siguiendo el protocolo VExUS, el 92% de los pacientes mostraron un grado 0, el 2% un grado 1 y el 6% un grado 2. CONCLUSIONES: El uso del ultrasonido portátil facilitó la caracterización cuantitativa de las características ecocardiográficas de la población estudiada. Este dispositivo podría ofrecer una mejor caracterización clínica que, a su vez, permita una optimización en la prescripción de medicamentos para la insuficiencia cardiaca y el ajuste de dosis de diuréticos según los hallazgos ecocardiográficos de congestión.


Subject(s)
Heart Failure , Pulmonary Edema , Humans , Male , Middle Aged , Female , Cross-Sectional Studies , Lung/diagnostic imaging , Pulmonary Edema/etiology , Ultrasonography/methods , Prognosis
3.
Arch. cardiol. Méx ; 94(1): 79-85, ene.-mar. 2024. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1556896

ABSTRACT

Resumen Antecedentes: En México aún es muy poco conocida la epidemiología de la insuficiencia cardiaca, sin embargo se sabe que la principal causa de ingresos hospitalarios en los pacientes con insuficiencia cardiaca es la congestión pulmonar y sistémica. Objetivo: Estimar el estado de congestión y evaluar la función cardiaca mediante el ultrasonido portátil en pacientes con insuficiencia cardiaca tratados en un centro de tercer nivel en México. Método: Se llevó a cabo un estudio observacional transversal. Se seleccionaron pacientes que acudieron a la Clínica de Insuficiencia Cardiaca del Instituto Nacional de Cardiología Ignacio Chávez en la Ciudad de México entre mayo y agosto de 2022. Se les sometió a una evaluación ultrasonográfica mediante un dispositivo portátil para valorar la congestión pulmonar y sistémica, así como la función y estructura cardiaca. Resultados: Se incluyeron de forma prospectiva 100 pacientes diagnosticados con insuficiencia cardiaca en el periodo de estudio. El 76% fueron hombres, con una edad mediana de 59 años (RIQ: 50-68 años). La mediana del FEVI registrada fue del 34% (RIQ: 27.0-43.5%). Al evaluar la congestión pulmonar, el 78% de los pacientes presentaron un patrón A y el 22% un patrón B. Siguiendo el protocolo VExUS, el 92% de los pacientes mostraron un grado 0, el 2% un grado 1 y el 6% un grado 2. Conclusiones: El uso del ultrasonido portátil facilitó la caracterización cuantitativa de las características ecocardiográficas de la población estudiada. Este dispositivo podría ofrecer una mejor caracterización clínica que, a su vez, permita una optimización en la prescripción de medicamentos para la insuficiencia cardiaca y el ajuste de dosis de diuréticos según los hallazgos ecocardiográficos de congestión.


Abstract Background: In Mexico, the epidemiology of heart failure is still not well understood. However, it is known that the primary cause of hospital admissions in patients with heart failure is pulmonary and systemic congestion. Objective: To estimate congestion status and assess cardiac function using portable ultrasound in patients with heart failure. Method: A cross-sectional observational study was conducted. Patients who attended the Heart Failure Clinic at the Ignacio Chávez National Cardiology Institute in Mexico City between May and August 2022 were selected. They underwent ultrasonographic evaluation using a portable device to assess pulmonary and systemic congestion, as well as cardiac function and structure. Results: One-hundred patients diagnosed with heart failure were prospectively included during the study period; 76% were male, with an average age of 59 years (range: 50-68 years). The recorded LVEF median was 34% (IQR: 27-43.5%). When evaluating pulmonary congestion, 78% of the patients showed a pattern A and 22% a pattern B. Following the VExUS protocol, 92% of the patients were at grade 0, 2% at grade 1, and 6% at grade 2. Conclusions: The use of the portable ultrasound facilitated the quantitative characterization of the echocardiographic features of the studied population. This device could provide better clinical characterization which, in turn, might allow for optimized drug prescription for heart failure and dose adjustments of diuretics based on echocardiographic congestion findings.

4.
Arch. cardiol. Méx ; 93(3): 336-344, jul.-sep. 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1513587

ABSTRACT

Abstract Objective: Associating comorbidities and cardiac symptoms that alter myocardial mechanical function could help clinicians to correctly identify at-risk population. Methods: We conducted a functional open population cross-sectional study of patients referred to a positron emission tomography/computed tomography unit in Mexico City for evaluation of myocardial function, perfusion, and coronary circulation. Ischemia was defined as a sum difference score ≥ 2. Association between comorbidities and cardiac symptoms was tested using logistic regression models and trend analysis. We performed an interaction analysis to evaluate the addition of any accompanying symptoms to comorbid conditions on impairment of myocardial function. Results: One thousand two hundred and seventy-three patients were enrolled, 66.1% male, with a mean age of 62.4 (± 12.7) years, 360 (28.7%) with ischemia, 925 (72.7%) with at least one comorbidity, and 676 (53.1%) had at least one associated cardiac symptom. Patients without ischemia, type 2 diabetes, arterial hypertension, and adverse cardiac symptoms were associated with adverse mechanical, perfusion, and coronary flow parameters. We observed a trend of a cumulative number of comorbidities and cardiac symptoms with increased ischemia and decreased coronary flow. Only in decreased left ventricular ejection fraction, we demonstrated an interaction effect between increased comorbidities and adverse symptoms. Conclusion: The high burden of comorbidities and symptoms in our population alters myocardial function regardless of the level of ischemia.


Resumen Objetivo: La asociación de comorbilidades y síntomas cardíacos que alteran la función miocárdica podría ayudar a los médicos a identificar correctamente a poblaciones de riesgo. Métodos: Se realizó un estudio transversal en población abierta de pacientes referidos a una unidad de PET/CT en la Ciudad de México para evaluación de la función miocárdica, perfusión y circulación coronaria. La isquemia se definió como una suma de diferencia de puntuación (SDS) ≥ 2. La asociación entre las comorbilidades y los síntomas cardíacos se fundamentó mediante modelos de regresión logística y análisis de tendencias. Realizamos un análisis de interacción para evaluar la adición de cualquier síntoma acompañante a condiciones comórbidas en el deterioro de la función miocárdica. Resultados: Se incluyeron 1.273 pacientes, 66,1% del sexo masculino, con una edad media de 62,4 (± 12.7) años, 360 (28,7%) con isquemia, 925 (72,7%) con al menos una comorbilidad y 676 (53,1%) con al menos una menos un síntoma cardíaco asociado. En pacientes sin isquemia, la diabetes mellitus tipo 2, la hipertensión arterial y los síntomas cardíacos adversos se asociaron con parámetros mecánicos, de perfusión y de flujo coronario adversos. Se observó una tendencia con el número acumulado de comorbilidades y síntomas cardíacos con aumento de la isquemia y disminución del flujo coronario. Solo en la disminución de la FEVI se demostró un efecto de interacción entre el aumento de las comorbilidades y los síntomas adversos. Conclusión: La alta carga de comorbilidades y síntomas en nuestra población altera la función miocárdica independientemente del nivel de isquemia.

5.
Rev. invest. clín ; 73(4): 222-230, Jul.-Aug. 2021. tab, graf
Article in English | LILACS | ID: biblio-1347568

ABSTRACT

Background: Information regarding diagnosis, treatment, and follow-up of patients with type 1 diabetes (PWT1D) in Mexico is limited. We developed an on-line platform Registro Nacional de Pacientes con Diabetes Tipo 1 (RENACED-DT1). Objective: The objective of the study was to describe the characteristics and healthcare of PWT1D registered in RENACED-DT1. Methods: Analyses of 965 PWT1D from July 2014 to January 2018 in different endocrinology clinics around Mexico. Results: Sixty-one percent were female with median age of 21 years, age at diagnosis 11 years, and disease duration at inclusion 8.2 years. Treatment regimen was basal-bolus in 61% and insulin-pumps in 21% (mainly in the private sector); 33.3% with self-monitoring of blood-glucose (SMBG) ≥4 times/day. Mean HbA1c at last follow-up was 8.7 ± 2.1% (72±23 mmol/mol), 18% had HbA1c < 7% (53 mmol/mol), and 35% > 9% (75 mmol/mol). SMBG ≥ 4 times/day was associated with HbA1c < 7%. Time since diagnosis > 10 years, female sex, BMI ≥ 30 kg/m2, SMBG < 4 times/day, and any hypoglycemia were associated with microvascular complications (p < 0.05). Conclusions: Percentage of patients achieving HbA1c < 7% is low; increased blood glucose monitoring is associated with better glycemic control. The achievement of optimal glycemic control must be increased to reduce the incidence of chronic complications and improve quality of life in PWT1D.


Subject(s)
Humans , Male , Female , Child , Adolescent , Young Adult , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/epidemiology , Quality of Life , Blood Glucose , Glycated Hemoglobin/analysis , Blood Glucose Self-Monitoring , Registries , Hypoglycemic Agents , Insulin , Mexico/epidemiology
6.
Rev Invest Clin ; 73(4): 222-230, 2021 05 04.
Article in English | MEDLINE | ID: mdl-33944861

ABSTRACT

BACKGROUND: Information regarding diagnosis, treatment, and follow-up of patients with type 1 diabetes (PWT1D) in Mexico is limited. We developed an on-line platform Registro Nacional de Pacientes con Diabetes Tipo 1 (RENACED-DT1). OBJECTIVE: The objective of the study was to describe the characteristics and healthcare of PWT1D registered in RENACED-DT1. METHODS: Analyses of 965 PWT1D from July 2014 to January 2018 in different endocrinology clinics around Mexico. RESULTS: Sixty-one percent were female with median age of 21 years, age at diagnosis 11 years, and disease duration at inclusion 8.2 years. Treatment regimen was basal-bolus in 61% and insulin-pumps in 21% (mainly in the private sector); 33.3% with self-monitoring of blood-glucose (SMBG) ≥4 times/day. Mean HbA1c at last follow-up was 8.7 ± 2.1% (72±23 mmol/mol), 18% had HbA1c < 7% (53 mmol/mol), and 35% > 9% (75 mmol/mol). SMBG ≥ 4 times/day was associated with HbA1c < 7%. Time since diagnosis > 10 years, female sex, BMI ≥ 30 kg/m2, SMBG < 4 times/day, and any hypoglycemia were associated with microvascular complications (p < 0.05). CONCLUSIONS: Percentage of patients achieving HbA1c < 7% is low; increased blood glucose monitoring is associated with better glycemic control. The achievement of optimal glycemic control must be increased to reduce the incidence of chronic complications and improve quality of life in PWT1D.


Subject(s)
Diabetes Mellitus, Type 1 , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , Child , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/therapy , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents , Insulin , Male , Mexico/epidemiology , Quality of Life , Registries , Young Adult
7.
Gac Med Mex ; 157(5): 522-530, 2021.
Article in English | MEDLINE | ID: mdl-35104275

ABSTRACT

BACKGROUND: Central aortic arterial stiffness (CAAS) is an independent cardiovascular risk factor. Insulin resistance (IR) contributes to CAAS-associated risk. OBJECTIVE: To evaluate the association between IR and CAAS in a Mexican population without diabetes. METHODS: IR was estimated with Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) and other surrogate markers (Metabolic score for IR [METS-IR], Quantitative Insulin Sensitivity Check Index [QUICKI], triglycerides/glucose index [TyG], TyG*body mass index [TyG*BMI] and triglycerides/high-density lipoprotein cholesterol ratio [TG/HDL-C]). CAAS was evaluated using carotid-femoral pulse wave velocity analysis (PWVcf) and the standardized augmentation index (AI-75). Bivariate correlations were made between surrogate markers and PWVcf. Increased CAAS was defined as PWVcf above the 90th percentile. Thresholds and area under the curve (AUC) were obtained for each surrogate marker in order to evaluate their performance in estimating increased CAAS. RESULTS: Three hundred and fifty-eight patients were included. A correlation was found between HOMA2-IR and PWVcf; this correlation was replicated with other surrogate markers. METS-IR and TyG*BMI had the highest degree of correlation with PWVcf. When adjustments were made for covariates, the correlations with TyG*BMI, METS-IR, HOMA2-IR and QUICKI maintained significance. HOMA2-IR showed the strongest correlation with AI-75. METS-IR and TyG showed the best AUC. Patients with prediabetes had the highest PWVcf. CONCLUSIONS: The relationship between IR and CAAS is present before the onset of diabetes; this association may entail higher cardiovascular risk.


ANTECEDENTES: La rigidez arterial central aórtica (RACA) es un factor de riesgo cardiovascular independiente. La resistencia a la insulina (RI) contribuye al riesgo asociado a RACA. OBJETIVO: Evaluar la asociación entre RI y RACA en una población mexicana sin diabetes. MÉTODOS: La RI se estimó con HOMA2-IR y (Homeostatic Model Assessment 2-Insulin Resistance) otros subrogados (METS-IR [Metabolic score for IR], QUICKI [Quantitative Insulin Sensitivity Check Index], TyG [ratio triglicéridos/glucosa], TyG*IMC [TyG*índice de masa corporal] y TG/HDL [ratio TG/lipoproteínas de alta densidad]). Se evaluó la RACA mediante el análisis de velocidad de onda del pulso carotídeo-femoral (VOPcf) y el índice de aumentación estandarizado (AI-75). Se realizaron correlaciones bivariante entre los subrogados y la VOPcf. RACA aumentada se definió como VOPcf arriba del percentil 90. Se obtuvieron puntos de corte y área bajo la curva (ABC) para cada subrogado para estimar RACA aumentada. RESULTADOS: Se incluyó 358 pacientes. Se encontró una correlación entre HOMA2-IR y VOPcf; esta correlación se replicó con los subrogados. METS-IR y TyG*IMC tuvieron el mayor grado de correlación con VOPcf. Al ajustar, las correlaciones con TyG*IMC, METS-IR, HOMA2-IR y QUICKI mantuvieron significancia. La correlación con AI-75 fue mayor para HOMA2-IR. METS-IR y TyG mostraron la mejor ABC. Los pacientes con prediabetes tuvieron mayor VOPcf. CONCLUSIONES: La relación entre la RI y la RACA está presente desde etapas no diabéticas; esta asociación puede conllevar mayor riesgo cardiovascular.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Vascular Stiffness , Blood Glucose , Diabetes Mellitus, Type 2/epidemiology , Humans , Pulse Wave Analysis
8.
PLoS One ; 15(12): e0244051, 2020.
Article in English | MEDLINE | ID: mdl-33326502

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, risk stratification has been used to decide patient eligibility for inpatient, critical and domiciliary care. Here, we sought to validate the MSL-COVID-19 score, originally developed to predict COVID-19 mortality in Mexicans. Also, an adaptation of the formula is proposed for the prediction of COVID-19 severity in a triage setting (Nutri-CoV). METHODS: We included patients evaluated from March 16th to August 17th, 2020 at the Instituto Nacional de Ciencias Médicas y Nutrición, defining severe COVID-19 as a composite of death, ICU admission or requirement for intubation (n = 3,007). We validated MSL-COVID-19 for prediction of mortality and severe disease. Using Elastic Net Cox regression, we trained (n = 1,831) and validated (n = 1,176) a model for prediction of severe COVID-19 using MSL-COVID-19 along with clinical assessments obtained at a triage setting. RESULTS: The variables included in MSL-COVID-19 are: pneumonia, early onset type 2 diabetes, age > 65 years, chronic kidney disease, any form of immunosuppression, COPD, obesity, diabetes, and age <40 years. MSL-COVID-19 had good performance to predict COVID-19 mortality (c-statistic = 0.722, 95%CI 0.690-0.753) and severity (c-statistic = 0.777, 95%CI 0.753-0.801). The Nutri-CoV score includes the MSL-COVID-19 plus respiratory rate, and pulse oximetry. This tool had better performance in both training (c-statistic = 0.797, 95%CI 0.765-0.826) and validation cohorts (c-statistic = 0.772, 95%CI 0.0.745-0.800) compared to other severity scores. CONCLUSIONS: MSL-COVID-19 predicts inpatient COVID-19 lethality. The Nutri-CoV score is an adaptation of MSL-COVID-19 to be used in a triage environment. Both scores have been deployed as web-based tools for clinical use in a triage setting.


Subject(s)
COVID-19/pathology , Severity of Illness Index , Adult , Aged , Area Under Curve , Body Mass Index , COVID-19/mortality , COVID-19/virology , Female , Hospital Mortality , Humans , Intensive Care Units , Kaplan-Meier Estimate , Male , Middle Aged , ROC Curve , Respiratory Rate , Risk Assessment , SARS-CoV-2/isolation & purification , Triage
9.
J Clin Hypertens (Greenwich) ; 21(8): 1063-1070, 2019 08.
Article in English | MEDLINE | ID: mdl-31318156

ABSTRACT

Hypertension is associated with insulin resistance (IR), metabolic syndrome (MS), and arterial stiffness. Non-insulin-based IR indexes were developed as tools for metabolic screening. Here, we aimed to evaluate the novel non-insulin-based Metabolic Score for IR (METS-IR) index for the prediction of incident hypertension and arterial stiffness evaluated using pulse wave velocity (PWV) analysis, compared with other non-insulin-based IR indexes. We evaluated two populations, a cross-sectional evaluation of high-risk individuals (n = 305) with a wide range of metabolic comorbidities and dyslipidemia in whom PWV measurement was performed and a 3-year prospective cohort of normotensive individuals (N = 6850). We observed a positive correlation between METS-IR and PWV in the cross-sectional cohort, which was higher compared with other non-insulin-based fasting IR indexes; furthermore, PWV values >75th percentile were associated with the upper tercile of METS-IR values. In the prospective cohort, we observed an increased risk for incident hypertension for the upper METS-IR tercile (METS-IR ≥ 46.42; HR: 1.81, 95% CI: 1.41-2.34), adjusted for known cardiovascular risk factors, and observed that METS-IR had greater increases in the predictive capacity for hypertension along with SBP and the Framingham Hypertension Risk Prediction Model compared with other non-insulin-based IR indexes. Therefore, METS-IR is a novel non-insulin-based IR index which correlates with arterial stiffness and is a predictor of incident hypertension, complementary to previously validated risk prediction models.


Subject(s)
Hypertension/physiopathology , Insulin Resistance/physiology , Metabolic Syndrome/physiopathology , Vascular Stiffness/physiology , Adult , Blood Pressure/physiology , Body Mass Index , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Case-Control Studies , Comorbidity , Cross-Sectional Studies , Dyslipidemias/complications , Dyslipidemias/diagnosis , Fasting/metabolism , Female , Humans , Hypertension/epidemiology , Incidence , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Pulse Wave Analysis/methods , Risk Factors
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