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	<front>
		<journal-meta>
			<journal-id journal-id-type="publisher-id">rac</journal-id>
			<journal-title-group>
				<journal-title>Revista argentina de cardiología</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Rev Argent Cardiol</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="ppub">0034-7000</issn>
			<issn pub-type="epub">1850-3748</issn>
			<publisher>
				<publisher-name>Sociedad Argentina de Cardiología</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.7775/rac.es.v93.i1.20864</article-id>
			<article-id pub-id-type="publisher-id">00010</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>ARTÍCULO DE REVISIÓN</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Enfermedad cardiovascular y depresión</article-title>
				<trans-title-group xml:lang="en">
					<trans-title>Cardiovascular Disease and Depression</trans-title>
				</trans-title-group>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3443-9025</contrib-id>
					<name>
						<surname>DÁVOLOS</surname>
						<given-names>IGNACIO</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
					<xref ref-type="fn" rid="fn1"><sup>MTSAC</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>PRIETO</surname>
						<given-names>OMAR</given-names>
					</name>
					<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
					<xref ref-type="fn" rid="fn1"><sup>MTSAC</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>ÁVALOS ODDI</surname>
						<given-names>ALEJANDRA</given-names>
					</name>
					<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
					<xref ref-type="fn" rid="fn1"><sup>MTSAC</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label>1</label>
				<institution content-type="original"> Unidad de Rehabilitación Cardiovascular, Hospital Cuenca Alta, Cañuelas, Provincia de Buenos Aires, Argentina </institution>
				<institution content-type="orgdiv1">Unidad de Rehabilitación Cardiovascular</institution>
				<institution content-type="normalized">Hospital Cuenca Alta</institution>
				<addr-line>
					<named-content content-type="city">Cañuelas</named-content>
                        <named-content content-type="state">Provincia de Buenos Aires</named-content>
				</addr-line>
				<country country="AR">Argentina</country>
				<email>ignacio.davolos@hotmail.com</email>
			</aff>
			<aff id="aff2">
				<label>2</label>
				<institution content-type="original"> Consejo de Epidemiología y Prevención Vascular SAC de la Sociedad Argentina de Cardiología </institution>
				<institution content-type="orgdiv1">Consejo de Epidemiología y Prevención Vascular SAC</institution>
				<institution content-type="normalized">Sociedad Argentina de Cardiología</institution>
				<country country="AR">Argentina</country>
			</aff>
			<aff id="aff3">
				<label>3</label>
				<institution content-type="original"> Área Corazón y Mujer de la Sociedad Argentina de Cardiología </institution>
				<institution content-type="orgdiv1">Área Corazón y Mujer</institution>
				<institution content-type="normalized">Sociedad Argentina de Cardiología</institution>
				<country country="AR">Argentina</country>
			</aff>
			<aff id="aff4">
				<label>4</label>
				<institution content-type="original"> Consejo de Aspectos Psicosociales de la Sociedad Argentina de Cardiología </institution>
				<institution content-type="orgdiv1">Consejo de Aspectos Psicosociales</institution>
				<institution content-type="normalized">Sociedad Argentina de Cardiología</institution>
				<country country="AR">Argentina</country>
			</aff>
			<author-notes>
				<corresp id="c1">
					<label>Dirección para separatas:</label> Unidad de Rehabilitación Cardiovascular Hospital Cuenca Alta, Cañuelas. Email: <email>ignacio.davolos@hotmail.com</email>
				</corresp>
				<fn fn-type="other" id="fn1">
					<p>Miembro Titular de la Sociedad Argentina de Cardiología</p>
				</fn>
				<fn fn-type="conflict" id="fn2">
					<label>Declaración de conflicto de intereses</label>
					<p> Los autores declaran no tener ningún conflicto de interés. (Ver formulario de conflicto de intereses de los autores en la web)</p>
				</fn>
			</author-notes>
			<!--<pub-date date-type="pub" publication-format="electronic">
				<day>26</day>
				<month>02</month>
				<year>2025</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<season>Jan-Feb</season>
				<year>2025</year>
			</pub-date>-->
			<pub-date pub-type="epub-ppub">
				<season>Jan-Feb</season>
				<year>2025</year>
			</pub-date>
			<volume>93</volume>
			<issue>1</issue>
			<fpage>61</fpage>
			<lpage>68</lpage>
			<history>
				<date date-type="received">
					<day>01</day>
					<month>11</month>
					<year>2024</year>
				</date>
				<date date-type="accepted">
					<day>10</day>
					<month>01</month>
					<year>2025</year>
				</date>
			</history>
			<permissions>
				<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by-nc/4.0/" xml:lang="es">
					<license-p>Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons</license-p>
				</license>
			</permissions>
			<abstract>
				<title>RESUMEN</title>
				<p>La depresión y las enfermedades cardiovasculares (ECV) son dos de las principales causas de discapacidad, que afectan la calidad de vida y aumentan los costos en salud. Existe una relación bidireccional entre ambas: la depresión es un factor de riesgo para desarrollar ECV y empeora el pronóstico en pacientes con ECV. La ECV a su vez aumenta la incidencia de depresión y empeora su pronóstico. Los factores biológicos implicados en ambas patologías incluyen la disfunción autonómica, la inflamación crónica y una mayor reactividad plaquetaria. Se recomienda la detección de la depresión en la consulta cardiológica, usando herramientas como el cuestionario de salud del paciente (PHQ-2). El tratamiento debe ser integral, y combinar antidepresivos, psicoterapia, ejercicio físico y prácticas de <italic>mindfulness</italic>. Inicialmente centrada en el ejercicio, la rehabilitación cardiovascular (RCV) ha evolucionado para abarcar la modificación del estilo de vida, lo cual ha demostrado mejorar la depresión y el bienestar general en pacientes con ECV.</p>
			</abstract>
			<trans-abstract xml:lang="en">
				<title>Abstract</title>
				<p>Depression and cardiovascular disease (CVD) are two leading causes of disability, impacting quality of life and increasing healthcare costs. There is a bidirectional relationship between them: depression is a risk factor for developing CVD and worsens prognosis in CVD patients. CVD in turn increases the incidence of depression and worsens its prognosis. Biological factors involved in both pathologies include autonomic dysfunction, chronic inflammation, and increased platelet reactivity. It is recommended to screen for depression during cardiology consultations, using tools such as the Patient Health Questionnaire (PHQ-2). Treatment should be comprehensive, combining antidepressants, psychotherapy, physical exercise, and mindfulness practices. Initially focused on exercise, cardiovascular rehabilitation (CR) has evolved to encompass lifestyle modification, which has been shown to improve depression and overall well-being in CVD patients</p>
			</trans-abstract>
			<kwd-group xml:lang="es">
				<title>Palabras clave:</title>
				<kwd>Enfermedades cardiovasculares </kwd>
				<kwd>Depresión </kwd>
				<kwd>Calidad de la atención médica</kwd>
			</kwd-group>
			<kwd-group xml:lang="en">
				<title>Key words:</title>
				<kwd>Cardiovascular disease</kwd>
				<kwd>Depression</kwd>
				<kwd>Health care quality</kwd>
			</kwd-group>
			<counts>
				<fig-count count="1"/>
				<table-count count="1"/>
				<equation-count count="0"/>
				<ref-count count="80"/>
				<page-count count="8"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<sec sec-type="intro">
			<title>INTRODUCCIÓN</title>
			<p>La depresión se caracteriza por una tristeza persistente y por la pérdida de interés en las actividades con las que normalmente se disfruta, así como por la incapacidad para llevar a cabo las actividades cotidianas, durante al menos dos semanas (OMS, 2021). (<xref ref-type="bibr" rid="B1">1</xref>) Según la Organización Mundial de la Salud, las enfermedades cardiovasculares (ECV) y los trastornos depresivos son las causas más frecuentes de discapacidad y afectan a 1 de cada 5 adultos durante su vida. (<xref ref-type="bibr" rid="B2">2</xref>) Los principales indicadores económicos y del sistema de salud revelan costos médicos crecientes, mayor utilización de los servicios de salud y pérdida de productividad en los pacientes con estas patologías. (<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref>) Además, las ECV y la depresión impactan profundamente en la calidad de vida general; (<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B8">8</xref>) la depresión es probablemente el factor más determinante de la calidad de vida en general. Existe una relación bidireccional entre la ECV y el desarrollo de trastornos depresivos. (<xref ref-type="bibr" rid="B9">9</xref>) La depresión es una de las principales causas de morbilidad y mala calidad de vida entre los pacientes con ECV y también se considera un factor de riesgo independiente para los principales eventos cardiovasculares adversos. (<xref ref-type="bibr" rid="B10">10</xref>) Por ello, resulta imprescindible conocer que la depresión es considerada un factor de riesgo para el desarrollo de ECV en individuos sanos, y en aquellos con diagnóstico de ECV implica peores resultados. Desde el año 2008, la <italic>American Heart Association</italic> (AHA) recomienda el rastreo sistemático de depresión en pacientes con ECV establecida, y en el año 2014, esta misma sociedad cardiológica agregó que la depresión debe ser considerada un factor de riesgo de mala evolución en pacientes con síndromes coronarios agudos. (<xref ref-type="bibr" rid="B1">1</xref>) Actualmente, la presencia de depresión luego de un infarto de miocardio se asocia independientemente con un riesgo 2 a 4 veces mayor de eventos cardiovasculares en el seguimiento. (<xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref>) Este riesgo es directamente proporcional a la gravedad de la depresión. (<xref ref-type="bibr" rid="B13">13</xref>) El riesgo es mayor en los pacientes refractarios al tratamiento antidepresivo. (<xref ref-type="bibr" rid="B14">14</xref>) Del mismo modo, la depresión se asocia con mayor tasa de eventos cardiovasculares luego de una cirugía de revascularización miocárdica (CRM). (<xref ref-type="bibr" rid="B15">15</xref>) </p>
			<p>Un estudio reciente entre pacientes que sufrieron un paro cardíaco extrahospitalario, mostró que aquellos a los que se les diagnosticó depresión o ansiedad tuvieron tasas de mortalidad a largo plazo más altas, y sugieren que la intervención de rehabilitación psicológica y neurológica para los sobrevivientes podría mejorar la supervivencia a largo plazo. (<xref ref-type="bibr" rid="B16">16</xref>)</p>
			<p>Al igual que las enfermedades crónicas no transmisibles, la depresión es considerada una patología sistémica y multidimensional, que afecta tanto el cuerpo como la mente, los vínculos, el desempeño laboral y la inserción social con una fuerte tendencia a la cronicidad y recurrencia. (<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>)</p>
		</sec>
		<sec sec-type="materials|methods">
			<title>MATERIAL Y MÉTODOS</title>
			<p>Se efectuó una revisión seleccionando los trabajos más significativos vinculados con este tópico. Se utilizaron los buscadores PubMed, Lilacs y Scielo, empleando las siguientes combinaciones de palabras en el título y resumen: “depression AND cardiovascular health”; “depression AND cardiology”; “depression AND cardiovascular disease”, y sus equivalentes en español. Además, la búsqueda se apoyó en la utilización de la herramienta que ofrece Open Alex. </p>
			<p>Fue tomado como referencia el Consenso de Aspectos Psicosociales en Enfermedad Cardiovascular redactado por el Consejo de Aspectos Psicosociales de la Sociedad Argentina de Cardiología (SAC). (<xref ref-type="bibr" rid="B19">19</xref>) Además, se utilizó el Documento de Posición para el Manejo del Estrés redactado por el grupo de trabajo del Consejo de Aspectos Psicosociales de la SAC. (<xref ref-type="bibr" rid="B20">20</xref>)</p>
		</sec>
		<sec sec-type="results">
			<title>RESULTADOS</title>
			<sec>
				<title><italic>Fisiopatología</italic></title>
				<p>Múltiples mecanismos biológicos se han identificado como contribuyentes al pronóstico menos favorable observado en pacientes que padecen tanto ECV como depresión. Entre estos factores, destacan la influencia de hábitos de vida poco saludables, alteraciones en el sistema nervioso autónomo, desequilibrios en el eje neuroendocrino, procesos inflamatorios crónicos, resistencia a la insulina y un aumento en la actividad plaquetaria. Estos mecanismos no sólo están presentes de manera simultánea, sino que interactúan entre sí de forma compleja, afectando de manera conjunta la función cardíaca y el estado neuropsiquiátrico. En consecuencia, la coocurrencia de depresión y ECV representa una interacción multifactorial que exacerba el riesgo de desenlaces adversos en salud. (<xref ref-type="bibr" rid="B21">21</xref>)</p>
				<p>Los pacientes con depresión son más susceptibles de incurrir en conductas que deterioran la salud, tales como el tabaquismo, la inactividad física y una dieta inadecuada, lo cual, junto a una baja adherencia a las intervenciones terapéuticas recomendadas, potencia la progresión de la ECV y disminuye las probabilidades de recuperación. (<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B23">23</xref>) La depresión y las formas prevalentes de ECV, como la insuficiencia cardíaca y la cardiopatía isquémica, comparten una fuerte relación con la disfunción autonómica, que actúa como un disparador de eventos cardiovasculares adversos. Esta disfunción autonómica se manifiesta a través de una mayor actividad simpática y menor actividad parasimpática, lo cual, en pacientes deprimidos, se traduce en un aumento de la frecuencia cardíaca en reposo, una reducción de la variabilidad de la frecuencia cardíaca y un incremento de la presión arterial. Estas alteraciones autonómicas contribuyen a patologías estructurales y funcionales tales como la hipertrofia ventricular izquierda, un mayor riesgo de arritmias ventriculares y disfunción endotelial, además de desajustes en la oferta y demanda de oxígeno en el tejido miocárdico, factores que aumentan el riesgo de isquemia miocárdica. (<xref ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr" rid="B25">25</xref>)</p>
				<p>Por otro lado, la depresión está estrechamente relacionada con la hiperactividad del eje hipotálamo-hipófiso-adrenal (HHA), que responde al estrés con la liberación de glucocorticoides, como el cortisol. En individuos deprimidos, la sobreestimulación del HHA lleva a una hipercortisolemia crónica, que está implicada en el desarrollo de hipertensión arterial y aterosclerosis precoz. El exceso de cortisol eleva el riesgo de eventos cardiovasculares trombóticos y de desarrollo de diabetes mellitus, complicaciones que pueden acelerar la progresión de la ECV. (<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref>)</p>
				<p>La función plaquetaria también presenta anomalías en pacientes deprimidos, que suelen exhibir una mayor reactividad plaquetaria, reflejada en la liberación de mediadores como el factor 4 plaquetario y la beta-tiroglobulina. Esta activación plaquetaria intensificada podría actuar como un factor adicional en la predisposición a eventos cardiovasculares agudos, al promover un ambiente protrombótico y, en consecuencia, favorecer la ocurrencia de eventos como el infarto agudo de miocardio. (<xref ref-type="bibr" rid="B29">29</xref>)</p>
				<p>En cuanto al perfil inflamatorio, se observa que los pacientes con depresión suelen tener niveles elevados de citoquinas proinflamatorias, como la interleuquina (IL)-1β, IL-6, y el factor de necrosis tumoral alfa (TNF-α), además de otros marcadores inflamatorios como la proteína C-reactiva (PCR) y moléculas de adhesión. Este estado inflamatorio crónico se considera un factor intermedio de gran relevancia en la patogénesis de la ECV, ya que promueve la disfunción endotelial, contribuye al desarrollo de aterosclerosis y aumenta el riesgo de eventos cardiovasculares mayores. La inflamación, entonces, emerge como un vínculo clave entre la depresión y la ECV, destacándose como uno de los mecanismos patológicos más influyentes en esta asociación. (<xref ref-type="bibr" rid="B30">30</xref>) Esta confluencia de factores sugiere que la relación entre depresión y ECV no es meramente aditiva, sino que responde a una interacción compleja que incrementa exponencialmente el riesgo cardiovascular en estos pacientes. En este contexto, la intervención en factores tanto físicos como psicológicos resulta crucial para mejorar el pronóstico de estos pacientes y reducir el riesgo de desenlaces adversos en salud.</p>
			</sec>
			<sec>
				<title><italic>Diagnóstico</italic></title>
				<sec>
					<title>Detección de depresión en la consulta cardiológica</title>
					<p>En las últimas décadas, las guías de práctica clínica sobre prevención de la ECV sugieren que se debe detectar la depresión y que se debe ofrecer tratamiento a los pacientes con depresión clínicamente significativa. (<xref ref-type="bibr" rid="B31">31</xref>) De manera similar, las directrices de la Sociedad Europea de Cardiología para el diagnóstico y tratamiento de la insuficiencia cardíaca sugieren que es de buena práctica la detección sistemática de la depresión a través de un cuestionario validado. (<xref ref-type="bibr" rid="B32">32</xref>) Sin embargo, la mayoría de los cardiólogos no cree tener un papel en la detección de la depresión en sus pacientes, y entiende que es responsabilidad de otra persona, como una enfermera, un programa de rehabilitación o el médico de familia. (<xref ref-type="bibr" rid="B33">33</xref>) Dado que la depresión es el principal factor impulsor de la calidad de vida en los pacientes cardíacos, los cardiólogos no deben eludir su responsabilidad de garantizar que se detecte la depresión. </p>
					<p>Los individuos que tuvieron un síndrome coronario agudo tienen una prevalencia de depresión entre dos y tres veces superior a la de la población general. La depresión suele reprimirse o suprimirse en el hospital debido a la negación inicial del afecto. Por lo tanto, los pacientes deben ser examinados nuevamente para detectar depresión uno o dos meses después del evento agudo. En estudios de hace ya 50 años los no negadores parecían deshacerse de sus miedos más lentamente y bajar la guardia más rápidamente que los negadores. A medida que se acercaba el momento del alta, las trayectorias de los puntajes de ansiedad y depresión presentaban un aumento. (<xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B35">35</xref>). Los pacientes con insuficiencia cardíaca crónica tienen una frecuencia de depresión entre tres y cinco veces superior a la de la población normal. Por lo tanto, todos estos pacientes deben ser examinados al menos una vez al año.</p>
					<p>La mayoría de los estudios se han centrado principalmente en la depresión mayor o en una escala de autoinforme que pretende &quot;diagnosticar&quot; la depresión mayor. Las escalas son herramientas que permiten evaluar y valorar la gravedad del cuadro depresivo, sumando el impacto de la depresión en la vida del paciente a la impresión subjetiva del profesional. Asimismo, permiten hacer el seguimiento de los síntomas y evaluar la respuesta a los tratamientos instaurados. Algunas se utilizan como un primer paso de detección que requiere un &quot;diagnóstico clínico&quot; posterior. Otros tienen propiedades psicométricas satisfactorias para &quot;diagnosticar&quot; el trastorno depresivo mayor en un solo paso. Los cuestionarios de autoinforme incluyen el Cuestionario de salud del paciente (PHQ), el Inventario de depresión de Beck (BDI), la Escala de ansiedad y depresión hospitalaria (HADS), la Escala de depresión cardíaca (CDS), y la Escala de depresión-10 del Centro de estudios epidemiológicos (CES-D). La mayoría de estas escalas están disponibles y han sido validadas en muchos idiomas diferentes. (<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B37">37</xref>,<xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B40">40</xref>) Actualmente, no se recomienda su empleo como herramientas diagnósticas.</p>
					<p>Un grupo asesor científico de la AHA sugirió que el PHQ-2 podría ser el más útil para realizar tamizaje (<italic>screening</italic>) de pacientes con ECV. (<xref ref-type="bibr" rid="B41">41</xref>) El PHQ-2 consta de dos ítems que interrogan sobre el estado de ánimo de los pacientes y su experiencia de anhedonia en las últimas 2 semanas. (<xref ref-type="fig" rid="f1">Figura 1</xref>) Los pacientes en quienes el cuestionario resulta positivo (puntaje ≥ 3) deberán evaluarse con el cuestionario de salud del paciente de 9 puntos (PHQ-9). El PHQ-9 amplía el PHQ-2 para incluir siete síntomas de depresión adicionales del DSM-IV. (<xref ref-type="bibr" rid="B42">42</xref>,<xref ref-type="bibr" rid="B43">43</xref>) Aquellos en que el PHQ-9 resulta positivo para depresión deben ser tratados con un enfoque multidisciplinario, basado en un equipo que incluya proveedores de atención primaria y médicos de salud mental. (<xref ref-type="bibr" rid="B44">44</xref>)</p>
					<p>
						<fig id="f1">
							<label>Figura 1</label>
							<caption>
								<title>Cuestionario de salud del paciente de dos elementos (PHQ-2)</title>
							</caption>
							<graphic xlink:href="1850-3748-rac-93-01-61-gf1.jpg"/>
						</fig>
					</p>
				</sec>
			</sec>
			<sec>
				<title><italic>Tratamiento</italic></title>
				<sec>
					<title>Intervenciones en pacientes con enfermedad cardiovascular</title>
					<p>El tratamiento de los trastornos depresivos en pacientes con enfermedad CV incluye estrategias de prevención primaria y de prevención secundaria. La prevención primaria se centra en identificar posibles factores de riesgo para la depresión. Son factores clínicos y sintomáticos que deberían alertar al profesional tratante sobre la existencia de un posible trastorno depresivo. (<xref ref-type="bibr" rid="B45">45</xref>,<xref ref-type="bibr" rid="B46">46</xref>) (<xref ref-type="table" rid="t1">Tabla 1</xref>). Existe una serie de recomendaciones para estos/as pacientes que incluyen desde la aplicación de programas selectivos de actividad física, dieta saludable, higiene del sueño, control de exposición a pantallas, hasta meditación y/o <italic>mindfulness</italic> (que promueve la atención plena, el centrarse exclusivamente en el presente). </p>
					<p>
						<table-wrap id="t1">
							<label>Tabla 1</label>
							<caption>
								<title>Factores clínicos y sintomáticos que permiten sospechar la existencia de un posible trastorno depresivo. (Fuente: Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. The Can J Psychiat. 2016; 61(9):524-39).(45)</title>
							</caption>
							<table frame="hsides" rules="groups">
								<colgroup>
									<col/>
									<col/>
								</colgroup>
								<thead>
									<tr style="border: 0; background-color:#ab0534;color:#ffffff;">
										<th align="left">Factores clínicos</th>
										<th align="left">Factores sintomáticos</th>
									</tr>
								</thead>
								<tbody>
									<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
										<td align="left">- Historia de depresión inexplicable</td>
										<td align="left">- Dolor crónico</td>
									</tr>
									<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
										<td align="left">- Antecedentes familiares de trastorno del ánimo</td>
										<td align="left">- Fatiga</td>
									</tr>
									<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
										<td align="left">- Adversidad psicosocial. Duelos complejos</td>
										<td align="left">- Trastornos del sueño</td>
									</tr>
									<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
										<td align="left">- Enfermedades crónicas (DBT, ECV, neurológicas)</td>
										<td align="left">- Ansiedad</td>
									</tr>
									<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
										<td align="left">- Patología psiquiátrica</td>
										<td align="left">- Período periparto</td>
									</tr>
									<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
										<td align="left">- Cambios hormonales en la mujer</td>
										<td align="left"> </td>
									</tr>
								</tbody>
							</table>
							<table-wrap-foot>
								<fn id="TFN1">
									<p>DBT: diabetes; ECV: enfermedad cardiovascular</p>
								</fn>
							</table-wrap-foot>
						</table-wrap>
					</p>
					<p>El abordaje de la depresión en adultos con ECV debería ser integral y contemplar todas las intervenciones psicoterapéuticas, psicosociales y farmacológicas que contribuyan a mejorar el bienestar y la capacidad funcional. (<xref ref-type="bibr" rid="B21">21</xref>) Los antidepresivos se emplean con mayor frecuencia que las intervenciones psicológicas o sociales, aunque las depresiones leves suelen responder positivamente a la psicoterapia y a otras alternativas terapéuticas. La búsqueda de la inmediatez y las resoluciones rápidas llevan a utilizar la farmacoterapia como primera medida, aunque los estudios han evidenciado que la combinación de psicoterapia, antidepresivos, ejercicio físico y prácticas de meditación o <italic>mindfulness</italic>, brindan mejor resultado a corto y largo plazo.</p>
				</sec>
			</sec>
			<sec>
				<title>Tratamiento no farmacológico de la depresión</title>
				<p>La efectividad de las intervenciones psicológicas y conductuales en la mejora de los resultados cardiovasculares ha mostrado variabilidad, reflejando la complejidad de la interacción entre el tratamiento psicológico y los desenlaces en salud cardíaca. Las terapias de base científica, como la terapia cognitivo-conductual (TCC), han mostrado resultados superiores en comparación con la atención habitual al reducir la intensidad de los síntomas depresivos en pacientes con insuficiencia cardíaca y diagnóstico de depresión, lo que sugiere un beneficio en el tratamiento conjunto de ambas patologías (<xref ref-type="bibr" rid="B47">47</xref>). Un metaanálisis que incluyó ensayos clínicos enfocados en intervenciones psicológicas y conductuales reveló que la psicoterapia se asocia con una reducción significativa de la mortalidad, hasta un 28% menor en comparación con los grupos de control, durante un periodo de seguimiento de dos años. (<xref ref-type="bibr" rid="B48">48</xref>) Además, los beneficios de la intervención psicológica fueron más evidentes en los pacientes que comenzaron el tratamiento dentro de los primeros dos meses tras un evento cardíaco agudo, lo que subraya la importancia del tiempo de intervención en la eficacia del tratamiento (<xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B50">50</xref>,<xref ref-type="bibr" rid="B51">51</xref>).</p>
				<p>El estudio ENRICHD (<italic>Enhancing Recovery in Coronary Heart Disease Patients</italic>) fue un ensayo clínico aleatorizado que exploró los efectos de la TCC en pacientes postinfarto de miocardio que presentaban síntomas de depresión o bajo apoyo social. Los pacientes fueron asignados a recibir atención convencional o una intervención de TCC, y los resultados mostraron mejoras significativas en indicadores psicosociales, como una reducción en los niveles de depresión y un incremento en el apoyo social percibido en el grupo tratado. Sin embargo, estos beneficios psicosociales no se tradujeron en una mejora en la supervivencia libre de eventos, sugiriendo que, aunque la TCC mejora ciertos aspectos de la calidad de vida, su impacto sobre la mortalidad o los eventos cardiovasculares recurrentes en este contexto específico puede ser limitado (<xref ref-type="bibr" rid="B52">52</xref>).</p>
				<p>El ejercicio físico ha emergido como una terapia adicional eficaz contra la depresión en pacientes con ECV. En un análisis secundario del estudio ENRICHD, se observó que los pacientes con depresión que mantenían una adherencia al ejercicio físico regular a los seis meses de un infarto de miocardio agudo tenían tasas de eventos graves (fatales y no fatales) entre un 38% y un 52% más bajas durante un seguimiento de cuatro años, en comparación con aquellos que no practicaban ejercicio de forma constante. Estos hallazgos destacan el valor potencial del ejercicio como medida complementaria para reducir la mortalidad y la incidencia de nuevos infartos en pacientes postinfarto, especialmente en aquellos con mayor riesgo de eventos adversos debido a síntomas depresivos o falta de apoyo social. (<xref ref-type="bibr" rid="B53">53</xref>) </p>
				<p>Además, prácticas como meditación y <italic>mindfulness</italic>, específicamente la terapia cognitiva basada en <italic>mindfulness</italic>, han sido recomendadas para prevenir la recurrencia de los cuadros depresivos. Diversos estudios han demostrado que esta última puede ayudar a los pacientes a manejar síntomas depresivos recurrentes y a reducir la reactividad emocional, lo cual podría ofrecer beneficios adicionales en la regulación emocional en pacientes con ECV, aunque la evidencia respecto a su impacto directo en la salud cardiovascular sigue siendo objeto de estudio (<xref ref-type="bibr" rid="B54">54</xref>,<xref ref-type="bibr" rid="B55">55</xref>,<xref ref-type="bibr" rid="B56">56</xref>,<xref ref-type="bibr" rid="B57">57</xref>,<xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B59">59</xref>,<xref ref-type="bibr" rid="B60">60</xref>,<xref ref-type="bibr" rid="B61">61</xref>,<xref ref-type="bibr" rid="B62">62</xref>,<xref ref-type="bibr" rid="B63">63</xref>,<xref ref-type="bibr" rid="B64">64</xref>,<xref ref-type="bibr" rid="B65">65</xref>,<xref ref-type="bibr" rid="B66">66</xref>,<xref ref-type="bibr" rid="B67">67</xref>).</p>
				<p>En conjunto, estas intervenciones sugieren que un enfoque integral que incluya tratamiento psicológico, ejercicio físico y prácticas de mindfulness puede contribuir a la mejora del estado mental y reducir el riesgo de eventos cardíacos recurrentes, si bien se requieren estudios adicionales para comprender plenamente la magnitud de sus efectos sobre la mortalidad y la progresión de la ECV en este grupo de pacientes.</p>
			</sec>
			<sec>
				<title>Rol de la rehabilitación cardiovascular</title>
				<p>Aunque inicialmente la rehabilitación cardiovascular (RCV) se introdujo como una intervención centrada en el ejercicio, posteriormente su alcance se amplió hasta convertirse en una intervención más integral en el estilo de vida, con el ejercicio como componente principal y cuatro elementos adicionales que incluyen modificación de la alimentación, manejo de los factores de riesgo, reducción del estrés y educación del paciente. Este desarrollo es relevante debido a la creciente evidencia disponible que sugiere que el cambio en el estilo de vida, incluyendo la higiene del sueño, ya sea de forma individual o en combinación con el ejercicio, pueden contribuir a mejorar la depresión. (<xref ref-type="bibr" rid="B68">68</xref>,<xref ref-type="bibr" rid="B69">69</xref>,<xref ref-type="bibr" rid="B70">70</xref>) Incluso en países con recursos médicos limitados, la modalidad virtual (basada en el hogar) ha demostrado impacto positivo tanto en calidad de vida como en bienestar psicológico (<xref ref-type="bibr" rid="B71">71</xref>). En una experiencia reciente de nuestro país, se observó que los efectos positivos de la derivación a Salud Mental complementaron los beneficios de la RCV. (<xref ref-type="bibr" rid="B72">72</xref>) Sin dudas, la mejoría anímica del individuo favorece la adherencia y el cumplimiento del tratamiento de rehabilitación. </p>
			</sec>
			<sec>
				<title>Tratamiento farmacológico de la depresión</title>
				<p>Al abordar los tratamientos psicofarmacológicos para la depresión en pacientes con ECV, es imprescindible basarse en guías clínicas confiables que orienten la práctica médica cotidiana. Entre ellas, se destacan la Guía para el Abordaje de la Depresión de la Red Canadiense para el Tratamiento de los Trastornos del Ánimo y Ansiedad (CANMAT) y las guías del Instituto Nacional para la Excelencia en Salud y Cuidado (NICE) del Reino Unido. (<xref ref-type="bibr" rid="B45">45</xref>,<xref ref-type="bibr" rid="B46">46</xref>) Las recomendaciones NICE son particularmente valiosas por su exhaustiva revisión de la evidencia científica; recomiendan el uso de antidepresivos en casos de depresión moderada a grave o cuando los síntomas persisten sin mejoría. Dentro de los antidepresivos, sugieren los inhibidores selectivos de la recaptación de serotonina (ISRS) como la opción preferida para su eficacia, aunque ningún ISRS ha demostrado superioridad sobre otro en términos generales. (<xref ref-type="bibr" rid="B73">73</xref>,<xref ref-type="bibr" rid="B74">74</xref>,<xref ref-type="bibr" rid="B75">75</xref>,<xref ref-type="bibr" rid="B76">76</xref>,<xref ref-type="bibr" rid="B77">77</xref>) Sin embargo, las particularidades de cada medicamento permiten elegir el más adecuado para cada perfil de paciente. (<xref ref-type="bibr" rid="B78">78</xref>)</p>
				<p>La efectividad de los ISRS en pacientes con ECV ha sido respaldada en ensayos clínicos. El ensayo SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), liderado por Glassman y colaboradores, evaluó su uso en 369 pacientes pos-SCA con depresión mayor. Aunque las puntuaciones de la Escala de Depresión de Hamilton (HAM-D) no mostraron diferencias significativas entre el grupo de sertralina y el de placebo, los pacientes tratados con sertralina obtuvieron mayores tasas de respuesta y mejoría clínica global en el grupo general. Además, los participantes con antecedentes de episodios depresivos o con trastornos depresivos de mayor gravedad experimentaron una mejoría más pronunciada en sus puntuaciones de HAM-D (<xref ref-type="bibr" rid="B74">74</xref>). Pizzi y colaboradores también observaron que la sertralina, comparada con el placebo, producía una mejora significativa en las puntuaciones de depresión en pacientes con enfermedad coronaria después de 20 semanas (<xref ref-type="bibr" rid="B75">75</xref>). En el estudio UPBEAT (Understanding Prognostic Benefits of Exercise and Antidepressant Therapy for Persons with Depression and Heart Disease), se comparó la sertralina, el ejercicio aeróbico y un placebo en una muestra de 101 pacientes con enfermedad coronaria y síntomas depresivos. Tanto el grupo de sertralina como el de ejercicio mostraron mejoras significativas en los síntomas depresivos en comparación con el placebo, sin una diferencia considerable entre los efectos de la sertralina y el ejercicio, lo que refuerza el valor del ejercicio como complemento en el tratamiento de la depresión en esta población. (<xref ref-type="bibr" rid="B77">77</xref>)</p>
				<p>Otro estudio reciente con un seguimiento extendido de 8,1 años y una muestra de 300 pacientes demostró que el escitalopram redujo la incidencia de eventos cardíacos adversos importantes después de un síndrome coronario agudo (SCA) en comparación con el placebo (40,9% frente a 53,6%) tras 24 semanas, confirmando su beneficio en este contexto. (<xref ref-type="bibr" rid="B79">79</xref>) </p>
				<p>El ensayo EsDEPACS (Escitalopram for Depression in ACS), que evaluó a 300 pacientes con SCA y depresión, mostró que el escitalopram fue superior al placebo en la reducción de los síntomas depresivos a las 24 semanas y hasta un año de seguimiento (<xref ref-type="bibr" rid="B80">80</xref>). Estos resultados refuerzan el perfil seguro y eficaz de los ISRS para el tratamiento de la depresión en pacientes con SCA reciente y enfermedad coronaria estable, haciéndolos adecuados para el manejo de la depresión en este grupo de alto riesgo. En conclusión, la evidencia respalda el uso de sertralina y escitalopram como tratamientos de elección en pacientes con depresión y enfermedad cardiovascular, proporcionando un beneficio tanto en la reducción de síntomas depresivos como en la disminución de eventos cardíacos adversos.</p>
			</sec>
		</sec>
		<sec sec-type="conclusions">
			<title>CONCLUSIÓN</title>
			<p>La relación entre la depresión y la salud cardiovascular es un área de creciente interés en la investigación médica, con un extenso cuerpo de evidencia que avala su vínculo bidireccional. La depresión puede exacerbar la morbilidad y mortalidad asociadas a trastornos cardiovasculares, además de afectar la calidad de vida y el pronóstico de estos pacientes. Es imperativo adoptar un enfoque multidimensional que incluya estrategias de evaluación y tratamiento de la salud mental en el contexto de la atención cardiovascular. La búsqueda de la inmediatez y las resoluciones rápidas llevan a utilizar la farmacoterapia como primera medida de tratamiento, aunque los estudios han evidenciado, en su mayoría, que la combinación de psicoterapia, antidepresivos, ejercicio físico y prácticas contemplativas, brindan mejor resultado a corto y largo plazo. Superar las disparidades y barreras con respecto a la salud mental implica intervenciones en políticas de salud, educación, capacitación, innovación en la atención médica y diversificación de la cardiología.</p>
			<p>En conclusión, el reconocimiento de la interacción entre la depresión y la salud cardiovascular es esencial para mejorar los resultados y fomentar un enfoque multidisciplinario en la atención médica, que integre adecuadamente la salud mental y cardiovascular.</p>
			<p><disp-quote>
				<p>“Toda afección de la mente acompañada de dolor o placer, esperanza o miedo, produce una agitación cuya influencia se extiende al corazón”</p>
			</disp-quote></p>
			<p><disp-quote>
				<p>Willam Harvey</p>
			</disp-quote></p>
		</sec>
	</body>
	<back>
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	</back>
	<!--<sub-article article-type="translation" id="s1" xml:lang="en">
		<front-stub>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>REVIEW ARTICLE</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Cardiovascular Disease and Depression</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3443-9025</contrib-id>
					<name>
						<surname>DÁVOLOS</surname>
						<given-names>IGNACIO</given-names>
					</name>
					<xref ref-type="aff" rid="aff5"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff6"><sup>2</sup></xref>
					<xref ref-type="fn" rid="fn3"><sup>MTSAC</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>PRIETO</surname>
						<given-names>OMAR</given-names>
					</name>
					<xref ref-type="aff" rid="aff7"><sup>3</sup></xref>
					<xref ref-type="aff" rid="aff8"><sup>4</sup></xref>
					<xref ref-type="fn" rid="fn3"><sup>MTSAC</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>ÁVALOS ODDI</surname>
						<given-names>ALEJANDRA</given-names>
					</name>
					<xref ref-type="aff" rid="aff7"><sup>3</sup></xref>
					<xref ref-type="aff" rid="aff8"><sup>4</sup></xref>
					<xref ref-type="fn" rid="fn3"><sup>MTSAC</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff5">
				<label>1</label>
				<institution content-type="original"> Cardiovascular Rehabilitation Unit , Hospital Cuenca Alta, Cañuelas, Provincia de Buenos Aires, Argentina </institution>
				<institution content-type="orgdiv1">Cardiovascular Rehabilitation Unit</institution>
				<institution content-type="orgname">Hospital Cuenca Alta</institution>
				<addr-line>
					<city>Cañuelas</city>
					<state>Provincia de Buenos Aires</state>
				</addr-line>
				<country country="AR">Argentina</country>
			</aff>
			<aff id="aff6">
				<label>2</label>
				<institution content-type="original"> Council on Epidemiology and Vascular Prevention SAC Sociedad Argentina de Cardiología </institution>
				<institution content-type="orgdiv1">Council on Epidemiology and Vascular Prevention SAC</institution>
				<institution content-type="orgname">Sociedad Argentina de Cardiología</institution>
			</aff>
			<aff id="aff7">
				<label>3</label>
				<institution content-type="original"> Heart and Women Area SAC Sociedad Argentina de Cardiología </institution>
				<institution content-type="orgdiv1">Heart and Women Area SAC</institution>
				<institution content-type="orgname">Sociedad Argentina de Cardiología</institution>
			</aff>
			<aff id="aff8">
				<label>4</label>
				<institution content-type="original"> Council on Psychosocial Aspects SAC Sociedad Argentina de Cardiología </institution>
				<institution content-type="orgdiv1">Council on Psychosocial Aspects SAC</institution>
				<institution content-type="orgname">Sociedad Argentina de Cardiología</institution>
			</aff>
			<author-notes>
				<corresp id="c2">
					<label> Correspondence:</label> Cardiovascular Rehabilitation Unit, Hospital Cuenca Alta, Cañuelas. Email: <email>ignacio.davolos@hotmail.com</email>
				</corresp>
				<fn fn-type="other" id="fn3">
					<p>Miembro Titular de la Sociedad Argentina de Cardiología</p>
				</fn>
				<fn fn-type="conflict" id="fn4">
					<label>Conflicts of interest</label>
					<p> None declared (See the authors' conflict of interest form on the website).</p>
				</fn>
			</author-notes>
			<abstract>
				<title>Abstract</title>
				<p>Depression and cardiovascular disease (CVD) are two leading causes of disability, impacting quality of life and increasing healthcare costs. There is a bidirectional relationship between them: depression is a risk factor for developing CVD and worsens prognosis in CVD patients. CVD in turn increases the incidence of depression and worsens its prognosis. Biological factors involved in both pathologies include autonomic dysfunction, chronic inflammation, and increased platelet reactivity. It is recommended to screen for depression during cardiology consultations, using tools such as the Patient Health Questionnaire (PHQ-2). Treatment should be comprehensive, combining antidepressants, psychotherapy, physical exercise, and mindfulness practices. Initially focused on exercise, cardiovascular rehabilitation (CR) has evolved to encompass lifestyle modification, which has been shown to improve depression and overall well-being in CVD patients</p>
			</abstract>
			<kwd-group xml:lang="en">
				<title>Key words:</title>
				<kwd> Cardiovascular disease</kwd>
				<kwd>Depression</kwd>
				<kwd>Health care quality.</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<sec sec-type="intro">
				<title>INTRODUCTION</title>
				<p>Depression is characterized by persistent sadness and loss of interest in activities normally enjoyed, as well as the inability to carry out daily activities, for at least two weeks (WHO, 2021). (<xref ref-type="bibr" rid="B81">1</xref>) According to the World Health Organization, cardiovascular disease (CVD) and depressive disorders are the most common causes of disability, affecting 1 in 5 adults during their lifetime. (<xref ref-type="bibr" rid="B82">2</xref>) Major economic and health system indicators reveal rising medical costs, increased utilization of health services, and loss of productivity in patients with these pathologies. (<xref ref-type="bibr" rid="B83">3</xref>,<xref ref-type="bibr" rid="B84">4</xref>,<xref ref-type="bibr" rid="B85">5</xref>,<xref ref-type="bibr" rid="B86">6</xref>) Furthermore, CVD and depression profoundly impact overall quality of life; (<xref ref-type="bibr" rid="B87">7</xref>,<xref ref-type="bibr" rid="B88">8</xref>) depression being probably the most important determinant of overall quality of life. There is a bidirectional relationship between CVD and the development of depressive disorders. (<xref ref-type="bibr" rid="B89">9</xref>) Depression is a major cause of morbidity and poor quality of life among patients with CVD and is also considered an independent risk factor for major adverse cardiovascular events. (<xref ref-type="bibr" rid="B90">10</xref>) Therefore, it is imperative to know that depression is considered a risk factor for the development of CVD in healthy individuals, and implies worse outcomes in those with a diagnosis of CVD . Since 2008, the American Heart Association (AHA) has recommended systematic screening for depression in patients with established CVD, and in 2014, the same cardiological society added that depression should be considered a risk factor for poor outcome in patients with acute coronary syndromes. (<xref ref-type="bibr" rid="B81">1</xref>) Currently, the presence of depression after myocardial infarction is independently associated with a 2- to 4-fold increased risk of cardiovascular events at follow-up. (<xref ref-type="bibr" rid="B91">11</xref>,<xref ref-type="bibr" rid="B92">12</xref>) This risk is directly proportional to the severity of depression. (<xref ref-type="bibr" rid="B93">13</xref>) The risk is higher in patients refractory to antidepressant treatment. (<xref ref-type="bibr" rid="B94">14</xref>) Similarly, depression is associated with a higher rate of cardiovascular events after coronary artery bypass grafting (CABG). (<xref ref-type="bibr" rid="B95">15</xref>) </p>
				<p>A recent study among patients who suffered out-of-hospital cardiac arrest showed that those diagnosed with depression or anxiety had higher long-term mortality rates, suggesting that psychological and neurological rehabilitation intervention for survivors may improve long-term survival. (<xref ref-type="bibr" rid="B96">16</xref>)</p>
				<p>Like chronic noncommunicable diseases, depression is considered a systemic and multidimensional pathology, affecting both body and mind, relationships, work performance and social insertion, with a strong tendency to chronicity and recurrence. (<xref ref-type="bibr" rid="B97">17</xref>,<xref ref-type="bibr" rid="B98">18</xref>)</p>
			</sec>
			<sec sec-type="methods">
				<title>METHODS</title>
				<p>A review was carried out by selecting the most significant papers related to this topic. The PubMed, Lilacs and Scielo search engines were used, employing the following word combinations in the title and abstract: &quot;depression AND cardiovascular health&quot;; &quot;depression AND cardiology&quot;; &quot;depression AND cardiovascular disease&quot;, and their equivalents in Spanish. In addition, the search was supported by the use of the tool offered by Open Alex. </p>
				<p>The Consensus on Psychosocial Aspects of Cardiovascular Disease written by the Council on Psychosocial Aspects of the Argentine Society of Cardiology (SAC) was used as reference. (<xref ref-type="bibr" rid="B99">19</xref>) In addition, the Position Document for Stress Management written by the working group of the Council on Psychosocial Aspects of the SAC was used. (<xref ref-type="bibr" rid="B100">20</xref>)</p>
			</sec>
			<sec sec-type="results">
				<title>RESULTS</title>
				<sec>
					<title><italic>Pathophysiology</italic></title>
					<p>Multiple biological mechanisms have been identified as contributing to the less favorable prognosis observed in patients with both CVD and depression. Among these factors are the influence of unhealthy lifestyle habits, alterations in the autonomic nervous system, imbalance in the neuroendocrine axis, chronic inflammatory processes, insulin resistance, and increased platelet activity. These mechanisms are not only present simultaneously, but also interact with each other in a complex manner, jointly affecting cardiac function and neuropsychiatric condition. Consequently, the co-occurrence of depression and CVD represents a multifactorial interaction that exacerbates the risk of adverse health outcomes. (<xref ref-type="bibr" rid="B101">21</xref>)</p>
					<p>Patients with depression are more susceptible to engage in behaviors that impair health, such as smoking, physical inactivity, and poor diet, which, together with low adherence to recommended therapeutic interventions, enhances CVD progression and decreases recovery probability. (<xref ref-type="bibr" rid="B102">22</xref>,<xref ref-type="bibr" rid="B103">23</xref>) Depression and prevalent forms of CVD, such as heart failure and ischemic heart disease, share a strong relationship with autonomic dysfunction, which acts as a trigger for adverse cardiovascular events. This autonomic dysfunction manifests itself through increased sympathetic activity and decreased parasympathetic activity, which, in depressed patients, translates into increased resting heart rate, reduced heart rate variability, and increased blood pressure. These autonomic alterations contribute to structural and functional pathologies such as left ventricular hypertrophy, increased risk of ventricular arrhythmias and endothelial dysfunction, in addition to mismatches in myocardial tissue oxygen supply and demand, factors that increase the risk of myocardial ischemia. (<xref ref-type="bibr" rid="B104">24</xref>,<xref ref-type="bibr" rid="B105">25</xref>)</p>
					<p>On the other hand, depression is closely related to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which responds to stress with the release of glucocorticoids, such as cortisol. In depressed individuals, overstimulation of the HPA axis leads to chronic hypercortisolemia, which is implicated in the development of arterial hypertension and early atherosclerosis. Excess cortisol elevates the risk of thrombotic cardiovascular events and the development of diabetes mellitus, complications that may accelerate CVD progression. (<xref ref-type="bibr" rid="B106">26</xref>,<xref ref-type="bibr" rid="B107">27</xref>,<xref ref-type="bibr" rid="B108">28</xref>)</p>
					<p>Platelet function is also abnormal in depressed patients, who tend to exhibit increased platelet reactivity, reflected in the release of mediators such as platelet factor 4 and beta-thyroglobulin. This intensified platelet activation could act as an additional factor in the predisposition to acute cardiovascular events, by promoting a prothrombotic environment and, consequently, favoring the occurrence of events such as acute myocardial infarction. (<xref ref-type="bibr" rid="B109">29</xref>)</p>
					<p>Regarding the inflammatory profile, patients with depression usually reveal elevated levels of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), in addition to other inflammatory markers such as C-reactive protein (CRP) and adhesion molecules. This chronic inflammatory condition is considered an intermediate factor of great relevance in the pathogenesis of CVD, as it promotes endothelial dysfunction, contributes to the development of atherosclerosis, and increases the risk of major cardiovascular events. Inflammation, then, emerges as a key link between depression and CVD, standing out as one of the most influential pathological mechanisms in this association. (<xref ref-type="bibr" rid="B110">30</xref>) This confluence of factors suggests that the relationship between depression and CVD is not merely additive but rather responds to a complex interaction that exponentially increases cardiovascular risk in these patients. In this context, intervention in both physical and psychological factors is crucial to improve the prognosis of these patients and reduce the risk of adverse health outcomes.</p>
				</sec>
				<sec>
					<title><italic>Diagnosis</italic></title>
					<sec>
						<title>Detection of depression in the cardiology consultation</title>
						<p>In recent decades, clinical practice guidelines on CVD prevention suggest that depression should be screened for and treatment offered to patients with clinically significant depression. (<xref ref-type="bibr" rid="B111">31</xref>) Similarly, the European Society of Cardiology guidelines for the diagnosis and treatment of heart failure suggest that it is good practice to routinely screen for depression using a validated questionnaire. (<xref ref-type="bibr" rid="B112">32</xref>) However, most cardiologists do not believe they have a role in screening for depression in their patients and understand that it is the responsibility of someone else, such as a nurse, rehabilitation program, or family physician. (<xref ref-type="bibr" rid="B113">33</xref>) Given that depression is the main factor of quality of life in cardiac patients, cardiologists should not shirk their responsibility to ensure that depression is detected. </p>
						<p>Individuals who have had an acute coronary syndrome have a prevalence of depression two to three times higher than that of the general population. Depression is often repressed or suppressed in the hospital because of the initial denial of affect. Therefore, patients should be re-screened for depression one to two months after the acute event. In studies as early as 50 years ago, non-deniers seemed to shed their fears more slowly and let down their guard more quickly than deniers. As discharge approached, the trajectories of anxiety and depression scores increased. (<xref ref-type="bibr" rid="B114">34</xref>,<xref ref-type="bibr" rid="B115">35</xref>) Patients with chronic heart failure have a frequency of depression 3 to 5 times higher than that of the normal population. Therefore, all these patients should be examined at least once a year.</p>
						<p>Most studies have focused primarily on major depression or on a self-report scale intended to &quot;diagnose&quot; major depression. Scales are tools to evaluate and assess the severity of the depressive condition, adding the impact of the depression on the patient's life to the subjective impression of the professional. They will also enable to monitor symptoms and evaluate response to treatment. Some are used as a first screening step requiring a subsequent &quot;clinical diagnosis&quot;. Others have satisfactory psychometric properties to &quot;diagnose&quot; major depressive disorder in a single step. Self-report questionnaires include the Patient Health Questionnaire (PHQ), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Cardiac Depression Scale (CDS), and the Center for Epidemiologic Studies Depression Scale-10 (CES-D). Most of these scales are available and have been validated in many different languages. (<xref ref-type="bibr" rid="B116">36</xref>,<xref ref-type="bibr" rid="B117">37</xref>,<xref ref-type="bibr" rid="B118">38</xref>,<xref ref-type="bibr" rid="B119">39</xref>,<xref ref-type="bibr" rid="B120">40</xref>) Currently, their use as diagnostic tools is not recommended.</p>
						<p>An AHA scientific advisory group suggested that the PHQ-2 may be the most useful questionnaire for screening patients with CVD. (<xref ref-type="bibr" rid="B121">41</xref>) The PHQ-2 consists of two items that ask about patients' mood and their experience of anhedonia in the last 2 weeks. (<xref ref-type="fig" rid="f2">Figure 1</xref>) Patients who screen positive (score ≥ 3) should be evaluated with the 9-item patient health questionnaire (PHQ-9). The PHQ-9 expands the PHQ-2 to include seven additional DSM-IV symptoms of depression. (<xref ref-type="bibr" rid="B122">42</xref>,<xref ref-type="bibr" rid="B123">43</xref>) Those who are tested positive for depression in the PHQ-9 should be treated with a multidisciplinary, team-based approach that includes primary care providers and mental health clinicians. (<xref ref-type="bibr" rid="B124">44</xref>)</p>
						<p>
							<fig id="f2">
								<label>Figure 1:</label>
								<caption>
									<title>Two-item Patient Health Questionnaire (PHQ-2).</title>
								</caption>
								<graphic xlink:href="1850-3748-rac-93-01-61-gf2.jpg"/>
							</fig>
						</p>
					</sec>
				</sec>
				<sec>
					<title><italic>Treatment</italic></title>
					<sec>
						<title>Interventions in patients with cardiovascular disease</title>
						<p>Treatment of depressive disorders in patients with CVD includes primary prevention and secondary prevention strategies. Primary prevention focuses on identifying possible risk factors for depression. These are clinical and symptomatic factors that should alert the treating professional to the existence of a possible depressive disorder. (<xref ref-type="bibr" rid="B125">45</xref>,<xref ref-type="bibr" rid="B126">46</xref>) (<xref ref-type="table" rid="t2">Table1</xref>) There are a series of recommendations for these patients that range from the application of selective physical activity programs, healthy diet, sleep hygiene, control of exposure to screens, to meditation and/or mindfulness (which promotes focusing exclusively on the present)</p>
						<p>
							<table-wrap id="t2">
								<label>Table 1</label>
								<caption>
									<title>Clinical and symptomatic factors leading to suspicion of possible depressive disorder. (Source: Parikh SV, et. al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. The Can J Psychiat. 2016; 61(9):524-39).(45)</title>
								</caption>
								<table frame="hsides" rules="groups">
									<colgroup>
										<col/>
										<col/>
									</colgroup>
									<thead>
										<tr style="border: 0; background-color:#ab0534;color:#ffffff;">
											<th align="left">Clinical factors</th>
											<th align="left">Symptomatic factors</th>
										</tr>
									</thead>
									<tbody>
										<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
											<td align="left"> -History of unexplained depression</td>
											<td align="left"> -Chronic pain</td>
										</tr>
										<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
											<td align="left"> -Family history of mood disorder </td>
											<td align="left"> </td>
										</tr>
										<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
											<td align="left"> -Psychosocial adversity. Complex grief </td>
											<td align="left"> -Sleep disorders</td>
										</tr>
										<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
											<td align="left"> -Chronic diseases (DM, CVD, neurological) </td>
											<td align="left"> -Anxiety</td>
										</tr>
										<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
											<td align="left"> -Psychiatric pathology </td>
											<td align="left"> -Peripartum period</td>
										</tr>
										<tr style="border-bottom: 2px solid white; background-color: #e3aea9;">
											<td align="left"> -Hormonal changes in women </td>
											<td align="left"> </td>
										</tr>
									</tbody>
								</table>
								<table-wrap-foot>
									<fn id="TFN2">
										<p>CVD: cardiovascular disease; DM: diabetes mellitus </p>
									</fn>
								</table-wrap-foot>
							</table-wrap>
						</p>
						<p>The approach to depression in adults with CVD should be comprehensive and include all psychotherapeutic, psychosocial and pharmacological interventions that contribute to improving well-being and functional capacity. (<xref ref-type="bibr" rid="B101">21</xref>) Antidepressants are used more frequently than psychological or social interventions, although mild depression usually responds positively to psychotherapy and other therapeutic alternatives. The search for immediacy and quick resolutions leads to the use of pharmacotherapy as the first measure, although studies have shown that the combination of psychotherapy, antidepressants, physical exercise and meditation or mindfulness practices provide better results in the short and long term.</p>
					</sec>
				</sec>
				<sec>
					<title>Non-pharmacological treatment of depression</title>
					<p>The effectiveness of psychological and behavioral interventions in improving cardiovascular outcomes has shown variability, reflecting the complexity of the interaction between psychological treatment and cardiac health outcomes. Science-based therapies, such as cognitive-behavioral therapy (CBT), have shown superior results compared with usual care in reducing the intensity of depressive symptoms in patients with heart failure and a diagnosis of depression, suggesting a benefit in the co-management of both conditions. (<xref ref-type="bibr" rid="B127">47</xref>) During a 2-year follow-up period, a meta-analysis that included clinical trials focused on psychological and behavioral interventions revealed that psychotherapy is associated with a significant reduction in mortality, up to 28% lower compared to control groups. (<xref ref-type="bibr" rid="B128">48</xref>) Furthermore, the benefits of psychological intervention were more evident in patients who started treatment within the first 2 months after an acute cardiac event, highlighting the importance of the time of intervention in treatment efficacy (<xref ref-type="bibr" rid="B129">49</xref>,<xref ref-type="bibr" rid="B130">50</xref>,<xref ref-type="bibr" rid="B131">51</xref>).</p>
					<p>The ENRICHD (Enhancing Recovery in Coronary Heart Disease Patients) study was a randomized clinical trial that explored the effects of CBT in post-myocardial infarction patients with symptoms of depression or low social support. Patients were assigned to receive either conventional care or a CBT intervention, and the results showed significant improvements in psychosocial indicators, such as a reduction in levels of depression and an increase in perceived social support in the treated group. However, these psychosocial benefits did not translate into improved event-free survival, suggesting that although CBT improves certain aspects of quality of life, its impact on mortality or recurrent cardiovascular events in this specific setting may be limited. (<xref ref-type="bibr" rid="B132">52</xref>) </p>
					<p>Physical exercise has emerged as an effective additional therapy against depression in patients with CVD. In a secondary analysis of the ENRICHD study, patients with depression who maintained adherence to regular physical exercise 6 months after acute myocardial infarction had 38% to 52% lower rates of major events (fatal and nonfatal) during a 4-year follow-up compared with those who did not exercise consistently. These findings highlight the potential value of exercise as an adjunctive measure to reduce mortality and the incidence of new infarctions in post-infarction patients, especially in those at increased risk of adverse events due to depressive symptoms or lack of social support. (<xref ref-type="bibr" rid="B133">53</xref>) </p>
					<p>In addition, practices such as meditation and mindfulness, specifically mindfulness-based cognitive therapy, have been recommended to prevent the recurrence of depressive symptoms. Several studies have shown that the latter can help patients manage recurrent depressive symptoms and reduce emotional reactivity, which could offer additional benefits in emotional regulation of patients with CVD, although the evidence regarding its direct impact on cardiovascular health is still under study. (<xref ref-type="bibr" rid="B134">54</xref>,<xref ref-type="bibr" rid="B135">55</xref>,<xref ref-type="bibr" rid="B136">56</xref>,<xref ref-type="bibr" rid="B137">57</xref>,<xref ref-type="bibr" rid="B138">58</xref>,<xref ref-type="bibr" rid="B139">59</xref>,<xref ref-type="bibr" rid="B140">60</xref>,<xref ref-type="bibr" rid="B141">61</xref>,<xref ref-type="bibr" rid="B142">62</xref>,<xref ref-type="bibr" rid="B143">63</xref>,<xref ref-type="bibr" rid="B144">64</xref>,<xref ref-type="bibr" rid="B145">65</xref>,<xref ref-type="bibr" rid="B146">66</xref>,<xref ref-type="bibr" rid="B147">67</xref>)</p>
					<p> Altogether, these interventions suggest that a comprehensive approach including psychological treatment, physical exercise, and mindfulness practices may contribute to the improvement of mental condition and reduce the risk of recurrent cardiac events, although further studies are required to fully understand the magnitude of their effects on mortality and CVD progression in this group of patients.</p>
				</sec>
				<sec>
					<title>Role of cardiovascular rehabilitation</title>
					<p>Although cardiovascular rehabilitation (CVR) was initially introduced as an exercise-focused intervention, its scope was subsequently broadened to become a more comprehensive lifestyle intervention, with exercise as the main component and four additional elements including dietary modification, risk factor management, stress reduction, and patient education. This development is relevant because of the growing evidence available suggesting that lifestyle change, including sleep hygiene, either individually or in combination with exercise, can contribute to improving depression. (<xref ref-type="bibr" rid="B148">68</xref>,<xref ref-type="bibr" rid="B149">69</xref>,<xref ref-type="bibr" rid="B150">70</xref>) Even in countries with limited medical resources, the virtual (home-based) modality has demonstrated positive impact on both quality of life and psychological well-being. (<xref ref-type="bibr" rid="B151">71</xref>) In a recent experience in our country, it was observed that the positive effects of referral to Mental Health complemented the benefits of CVR. (<xref ref-type="bibr" rid="B152">72</xref>) Undoubtedly, the improvement in the individual's mood favors adherence and compliance with rehabilitation treatment</p>
				</sec>
				<sec>
					<title>Pharmacological treatment of depression</title>
					<p>When addressing psychopharmacological treatments for depression in patients with CVD, it is essential to rely on sound clinical guidelines to guide daily medical practice. These include the Canadian Network for the Management of Mood and Anxiety Disorders (CANMAT) Guidelines for the Management of Depression and the UK National Institute for Health and Care Excellence (NICE). (<xref ref-type="bibr" rid="B125">45</xref>,<xref ref-type="bibr" rid="B126">46</xref>) The NICE guidelines are particularly valuable because of their comprehensive review of scientific evidence. They recommend the use of antidepressants in cases of moderate to severe depression or when symptoms persist without improvement. Within the antidepressants, they suggest selective serotonin reuptake inhibitors (SSRIs) as the preferred option for efficacy, although no SSRI has demonstrated superiority over another in general terms. (<xref ref-type="bibr" rid="B153">73</xref>,<xref ref-type="bibr" rid="B154">74</xref>,<xref ref-type="bibr" rid="B155">75</xref>,<xref ref-type="bibr" rid="B156">76</xref>,<xref ref-type="bibr" rid="B157">77</xref>) However, the characteristics of each drug allow choosing the most appropriate one for each patient’s profile. (<xref ref-type="bibr" rid="B158">78</xref>)</p>
					<p>The effectiveness of SSRIs in patients with CVD has been supported in clinical trials. The SADHART (Sertraline Antidepressant Heart Attack Randomized Trial) trial</p>
					<p>led by Glassman et. al., evaluated their use in 369 post-ACS patients with major depression. Although the Hamilton Depression Scale (HAM-D) scores showed no significant differences between the sertraline and placebo groups, sertraline-treated patients had higher response rates and clinical improvement in the overall group. In addition, participants with a history of depressive episodes or with depressive disorders of greater severity experienced a more pronounced improvement in their HAM-D scores. (<xref ref-type="bibr" rid="B154">74</xref>) Pizzi et. al. also observed that sertraline, compared with placebo, produced a significant improvement in depression scores in patients with coronary artery disease after 20 weeks. (<xref ref-type="bibr" rid="B155">75</xref>) In the UPBEAT (Understanding Prognostic Benefits of Exercise and Antidepressant Therapy for Persons with Depression and Heart Disease) study, sertraline, aerobic exercise, and placebo were compared in a sample of 101 patients with coronary artery disease and depressive symptoms. Both the sertraline and exercise groups showed significant improvements in depressive symptoms compared to placebo, with no considerable difference between the effects of sertraline and exercise, reinforcing the value of exercise as an adjunct in the treatment of depression in this population. (<xref ref-type="bibr" rid="B157">77</xref>)</p>
					<p>Another recent study with an extended follow-up of 8.1 years and a sample of 300 patients showed that escitalopram reduced the incidence of major adverse cardiac events after acute coronary syndrome (ACS) compared to placebo (40.9% vs. 53.6%) after 24 weeks, confirming its benefit in this context. (<xref ref-type="bibr" rid="B159">79</xref>) </p>
					<p>The EsDEPACS (Escitalopram for Depression in ACS) trial, which evaluated 300 patients with ACS and depression, showed that escitalopram was superior to placebo in reducing depressive symptoms at 24 weeks and up to 1 year of follow-up. (<xref ref-type="bibr" rid="B80">80</xref>) These results reinforce the safe and effective profile of SSRIs for the treatment of depression in patients with recent ACS and stable coronary artery disease, making them suitable for the management of depression in this high-risk group. In conclusion, the evidence supports the use of sertraline and escitalopram as treatments of choice in patients with depression and cardiovascular disease, providing a benefit both in the reduction of depressive symptoms and in the reduction of adverse cardiac events.</p>
				</sec>
			</sec>
			<sec sec-type="conclusions">
				<title>CONCLUSION</title>
				<p>The relationship between depression and cardiovascular health is an area of growing interest in medical research, with an extensive body of evidence supporting its bidirectional link. Depression can exacerbate morbidity and mortality associated with cardiovascular disorders, in addition to affecting the quality of life and prognosis of these patients. It is imperative to adopt a multidimensional approach that includes mental health assessment and treatment strategies in the context of cardiovascular care. The search for immediacy and quick resolutions leads to the use of pharmacotherapy as the first treatment measure, although studies have mostly evidenced that the combination of psychotherapy, antidepressants, physical exercise and contemplative practices, provide better short- and long-term outcomes. Overcoming mental health disparities and barriers involves health policy interventions, education, training, innovation in medical care, and diversification of cardiology.</p>
				<p>In conclusion, recognition of the interaction between depression and cardiovascular health is essential to improve outcomes and encourage a multidisciplinary approach to care appropriately integrating mental and cardiovascular health.</p>
				<p><disp-quote>
					<p><italic>&quot;Every affection of the mind accompanied by pain or pleasure, hope or fear, produces an agitation whose influence extends to the heart.&quot;</italic></p>
				</disp-quote></p>
				<p><disp-quote>
					<p><italic>Willam Harvey</italic></p>
				</disp-quote></p>
			</sec>
		</body>
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