RESUMEN
BACKGROUND & AIMS: Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. METHODS: Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450 mg and 900 mg) on FMD was also investigated. RESULTS: We observed a bi-phasic FMD response after low and high polyphenol, (89 mg and 310 mg CGA) intake, with increases at 1 (1.10 ± 0.43% and 1.34 ± 0.62%, respectively) and 5 (0.79% ± 0.32 and 1.52% ± 0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-feruloylquinic acid and ferulic-4'-O-sulfate at 1 h and isoferulic-3'-O-glucuronide and ferulic-4'-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p = 0.06) and concomitant appearance of plasma metabolites. CONCLUSIONS: Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites. STUDY REGISTRATION: The National Institutes of Health (NIH) on ClinicalTrials.govNCT01813981 and NCT01772784.
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Ácido Clorogénico/administración & dosificación , Café , Endotelio Vascular/efectos de los fármacos , Polifenoles/administración & dosificación , Ácido Quínico/análogos & derivados , Adolescente , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Índice de Masa Corporal , Ácido Clorogénico/sangre , Estudios Cruzados , Humanos , Masculino , Persona de Mediana Edad , Polifenoles/sangre , Ácido Quínico/administración & dosificación , Ácido Quínico/sangre , Método Simple Ciego , Adulto JovenRESUMEN
Epidemiological studies have shown an association between pathologic events occurring during fetal/perinatal life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called developmental origin of adult disease hypothesis. More recently, evidence has been provided that the pulmonary circulation is also an important target for the developmental programming of adult disease in both experimental animal models and in humans. Here we will review this evidence and provide insight into mechanisms that may play a pathogenic role.
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Vasos Sanguíneos/embriología , Vasos Sanguíneos/fisiopatología , Desarrollo Fetal , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/fisiopatología , Hipoxia/complicaciones , Hipoxia/fisiopatología , Animales , Ambiente , Humanos , Modelos BiológicosRESUMEN
Epidemiological studies have shown an association between pathologic events occurring during early life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called fetal programming of adult disease hypothesis. In line with this hypothesis, short-term exposure to hypoxia after birth predisposes to exaggerated hypoxic pulmonary vasoconstriction later in life in rats, and transient perinatal hypoxia predisposes to exaggerated pulmonary hypertension during short-term exposure to high altitude in humans. Along the same lines, in recent studies in Bolivian high-altitude dwellers, we found that preeclampsia predisposes the offspring to pulmonary and systemic endothelial dysfunction possibly related to impaired NO bioavailability and augmented oxidative stress. Very recent data from our lab suggest that assisted reproductive technologies may represent another important example consistent with this hypothesis. The mechanisms underpinning the developmental origin of this vascular dysfunction are poorly understood. Increasing evidence suggests that epigenetic alterations, such as DNA methylation or histone acetylation may play a role.
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Sistema Cardiovascular/metabolismo , Epigénesis Genética , Animales , Enfermedades Cardiovasculares/embriología , Enfermedades Cardiovasculares/genética , Modelos Animales de Enfermedad , Ambiente , Desarrollo Fetal , HumanosRESUMEN
Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease in general. Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world affecting many millions of high-altitude dwellers. It is characterized by exaggerated chronic hypoxemia, erythrocytosis, and mild pulmonary hypertension. In later stages these patients often present with right heart failure and are predisposed to systemic cardiovascular disease, but the underlying mechanisms are poorly understood. Here, we present recent new data providing insight into underlying mechanisms that may cause these complications.
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Mal de Altura/patología , Sistema Cardiovascular/metabolismo , Adaptación Fisiológica , Sistema Cardiovascular/fisiopatología , Enfermedad Crónica , Humanos , Hipoxia/complicaciones , Hipoxia/fisiopatología , VasoconstricciónRESUMEN
OBJECTIVE: To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN: We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS: Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS: Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities.
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Mal de Altura/complicaciones , Trastornos del Conocimiento/etiología , Enfermedad Aguda , Adolescente , Altitud , Niño , Enfermedad Crónica , Cognición/fisiología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , Hipoxia/complicaciones , Masculino , Trastornos de la Memoria , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep-disordered breathing (SDB) frequently occurs at high altitude. At low altitude, SDB causes vascular dysfunction. Moreover, in SDB, transient elevations of right-sided cardiac pressure may cause right-to-left shunting in the presence of a patent foramen ovale (PFO) and, in turn, further aggravate hypoxemia and pulmonary hypertension. We speculated that SDB and nocturnal hypoxemia are more pronounced in patients with CMS compared with healthy high-altitude dwellers, and are related to vascular dysfunction. METHODS: We performed overnight sleep recordings, and measured systemic and pulmonary artery pressure in 23 patients with CMS (mean ± SD age, 52.8 ± 9.8 y) and 12 healthy control subjects (47.8 ± 7.8 y) at 3,600 m. In a subgroup of 15 subjects with SDB, we assessed the presence of a PFO with transesophageal echocardiography. RESULTS: The major new findings were that in patients with CMS, (1) SDB and nocturnal hypoxemia was more severe (P < .01) than in control subjects (apnea-hypopnea index [AHI], 38.9 ± 25.5 vs 14.3 ± 7.8 number of events per hour [nb/h]; arterial oxygen saturation, 80.2% ± 3.6% vs 86.8% ± 1.7%, CMS vs control group), and (2) AHI was directly correlated with systemic blood pressure (r = 0.5216; P = .001) and pulmonary artery pressure (r = 0.4497; P = .024). PFO was associated with more severe SDB (AHI, 48.8 ± 24.7 vs 14.8 ± 7.3 nb/h; P = .013, PFO vs no PFO) and hypoxemia. CONCLUSIONS: SDB and nocturnal hypoxemia are more severe in patients with CMS than in control subjects and are associated with systemic and pulmonary vascular dysfunction. The presence of a PFO appeared to further aggravate SDB. Closure of the PFO may improve SDB, hypoxemia, and vascular dysfunction in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.
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Mal de Altura/epidemiología , Altitud , Foramen Oval Permeable/epidemiología , Hipertensión Pulmonar/epidemiología , Hipoxia/epidemiología , Síndromes de la Apnea del Sueño/epidemiología , Adulto , Mal de Altura/fisiopatología , Presión Sanguínea , Bolivia/epidemiología , Estudios de Casos y Controles , Enfermedad Crónica , Ecocardiografía Transesofágica , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/fisiopatología , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Hipoxia/fisiopatología , Masculino , Persona de Mediana Edad , Polisomnografía , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño/fisiopatologíaRESUMEN
UNLABELLED: Obstructive sleep apnea (OSA) is a frequent syndrome characterized by intermittent hypoxemia and increased prevalence of arterial hypertension and cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is associated with increased number of apneas and more severe oxygen desaturation. We hypothesized that PFO closure improves sleep-disordered breathing and, in turn, has favorable effects on vascular function and arterial blood pressure. In 40 consecutive patients with newly diagnosed OSA, we searched for PFO. After initial cardiovascular assessment, the 14 patients with PFO underwent initial device closure and the 26 without PFO served as control group. Conventional treatment for OSA was postponed for 3 months in both groups, and polysomnographic and cardiovascular examinations were repeated at the end of the follow-up period. PFO closure significantly improved the apnea-hypopnea index (ΔAHI -7.9±10.4 versus +4.7±13.1 events/h, P=0.0009, PFO closure versus control), the oxygen desaturation index (ΔODI -7.6±16.6 versus +7.6±17.0 events/h, P=0.01), and the number of patients with severe OSA decreased significantly after PFO closure (79% versus 21%, P=0.007). The following cardiovascular parameters improved significantly in the PFO closure group, although remained unchanged in controls: brachial artery flow-mediated vasodilation, carotid artery stiffness, nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg, P=0.04, respectively), blood pressure dipping, and left ventricular diastolic function. In conclusion, PFO closure in OSA patients improves sleep-disordered breathing and nocturnal oxygenation. This translates into an improvement of endothelial function and vascular stiffening, a decrease of nighttime blood pressure, restoration of the dipping pattern, and improvement of left ventricular diastolic function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01780207.
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Presión Sanguínea/fisiología , Sistema Cardiovascular/fisiopatología , Foramen Oval Permeable/cirugía , Dispositivo Oclusor Septal , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Anciano , Procedimientos Quirúrgicos Cardíacos/instrumentación , Sistema Cardiovascular/diagnóstico por imagen , Ecocardiografía Transesofágica , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Resultado del Tratamiento , Rigidez Vascular/fisiología , Función Ventricular Izquierda/fisiologíaRESUMEN
Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 µM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 µM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.
Asunto(s)
Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Melatonina/farmacología , Arterias Mesentéricas/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Técnicas Reproductivas Asistidas , Acetilcolina/farmacología , Animales , Medios de Cultivo , Metilación de ADN/efectos de los fármacos , Técnicas de Cultivo de Embriones , Hipertensión/prevención & control , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Regiones Promotoras Genéticas/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.
Asunto(s)
Técnicas Reproductivas Asistidas/efectos adversos , Disfunción Ventricular Derecha/epidemiología , Adolescente , Altitud , Peso al Nacer , Niño , Femenino , Fertilización In Vitro , Estudios de Seguimiento , Pruebas de Función Cardíaca , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Oxígeno/sangre , Presión Esfenoidal Pulmonar , Volumen Sistólico , Válvula Tricúspide/diagnóstico por imagen , Ultrasonografía , Disfunción Ventricular Derecha/diagnóstico por imagen , Función Ventricular IzquierdaRESUMEN
Epidemiological studies demonstrate a relationship between pathological events during foetal development and future cardiovascular risk and the term 'foetal programming of cardiovascular disease' has been coined to describe this phenomenon. The use of assisted reproductive technologies (ARTs) is growing exponentially and 2-5% of children are now born by this procedure. Emerging evidence indicates that ART represents a novel important example of foetal programming. Assisted reproductive technology may modify the cardiovascular phenotype in two ways: (i) ART involves manipulation of the early embryo which is exquisitely sensitive to environmental insults. In line with this concern, ART alters vascular and cardiac function in children and studies in mice show that ART alters the cardiovascular phenotype by epigenetic alterations related to suboptimal culture conditions. (ii) Assisted reproductive technology markedly increases the risk of foetal insults that augment cardiovascular risk in naturally conceived individuals and are expected to have similar consequences in the ART population. Given the young age of the ART population, it will take another 20-30 years before data on cardiovascular endpoints will be available. What is clear already, however, is that ART emerges as an important cardiovascular risk factor. This insight requires us to revise notions on ART's long-term safety and to engage on a debate on its future. There is an urgent need to better understand the mechanisms underpinning ART-induced alteration of the cardiovascular phenotype, improve the procedure and its long-term safety, and, while awaiting this aim, not to abandon medicine's fundamental principle of doing no harm (to future children) and use ART parsimoniously.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Técnicas Reproductivas Asistidas/efectos adversos , Animales , Enfermedades Cardiovasculares/prevención & control , Niño , Modelos Animales de Enfermedad , Epigénesis Genética/fisiología , Femenino , Desarrollo Fetal/fisiología , Predicción , Humanos , Ratones , Óxido Nítrico Sintasa de Tipo III/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Técnicas Reproductivas Asistidas/tendencias , Factores de Riesgo , Remodelación Vascular/fisiologíaRESUMEN
BACKGROUND: There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS: We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS: The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS: These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.
Asunto(s)
Altitud , Foramen Oval Permeable/complicaciones , Ventrículos Cardíacos/diagnóstico por imagen , Hipertensión Pulmonar/epidemiología , Resistencia Vascular , Disfunción Ventricular Derecha/epidemiología , Función Ventricular Derecha/fisiología , Ecocardiografía Transesofágica , Foramen Oval Permeable/diagnóstico , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Prevalencia , Suiza/epidemiología , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
AIMS: Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS: In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS: Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.
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Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Arteria Braquial/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Arteria Pulmonar/efectos de los fármacos , Técnicas Reproductivas Asistidas/efectos adversos , Vitamina E/uso terapéutico , Adolescente , Factores de Edad , Altitud , Presión Arterial/efectos de los fármacos , Arteria Braquial/metabolismo , Arteria Braquial/fisiopatología , Niño , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Masculino , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estudios Prospectivos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/fisiopatología , Recuperación de la Función , Suiza , Factores de Tiempo , Resultado del Tratamiento , Vasodilatación/efectos de los fármacosRESUMEN
Epidemiological studies in humans have demonstrated a relationship between pathological events during fetal development and increased cardiovascular risk later in life and have led to the so called "Fetal programming of cardiovascular disease hypothesis". The recent observation of generalised vascular dysfunction in young apparently healthy children conceived by assisted reproductive technologies (ART) provides a novel and potentially very important example of this hypothesis. This review summarises recent data in ART children demonstrating premature subclinical atherosclerosis in the systemic circulation and pulmonary vascular dysfunction predisposing to exaggerated hypoxia-induced pulmonary hypertension. These problems appear to be related to the ART procedure per se. Studies in ART mice demonstrating premature vascular aging and arterial hypertension further demonstrate the potential of ART to increase cardiovascular risk and have allowed to unravel epigenetic alterations of the eNOS gene as an underpinning mechanism. The roughly 25% shortening of the life span in ART mice challenged with a western style high-fat-diet demonstrates the potential importance of these alterations for the long-term outcome. Given the young age of the ART population, data on cardiovascular endpoints will not be available before 20 to 30 years from now. However, already now cohort studies of the ART population are needed to early detect cardiovascular alterations with the aim to prevent or at least optimally treat cardiovascular complications. Finally, a debate needs to be engaged on the future of ART and the consequences of its exponential growth for public health.
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Enfermedades Cardiovasculares/embriología , Enfermedades Cardiovasculares/genética , Endotelio Vascular/fisiopatología , Epigénesis Genética , Técnicas Reproductivas Asistidas/efectos adversos , Animales , Niño , Metilación de ADN , Endotelio Vascular/embriología , Desarrollo Fetal , Humanos , Óxido Nítrico Sintasa de Tipo III/genéticaRESUMEN
OBJECTIVES: This study sought to determine the vascular anatomical eligibility for catheter-based renal artery denervation (RDN) in hypertensive patients. BACKGROUND: Arterial hypertension is the leading cardiovascular risk factor for stroke and mortality globally. Despite substantial advances in drug-based treatment, many patients do not achieve target blood pressure levels. To improve the number of controlled patients, novel procedure- and device-based strategies have been developed. RDN is among the most promising novel techniques. However, there are few data on the vascular anatomical eligibility. METHODS: We retrospectively analyzed 941 consecutive hypertensive patients undergoing coronary angiography and selective renal artery angiography between January 1, 2010, and May 31, 2012. Additional renal arteries were divided into 2 groups: hilar (accessory) and polar (aberrant) arteries. Anatomical eligibility for RDN was defined according to the current guidelines: absence of renal artery stenosis, renal artery diameter ≥4 mm, renal artery length ≥20 mm, and only 1 principal renal artery. RESULTS: A total of 934 hypertensive patients were evaluable. The prevalence of renal artery stenosis was 10% (n = 90). Of the remaining 844 patients without renal artery stenosis, 727 (86%) had nonresistant hypertension and 117 (14%) had resistant hypertension; 62 (53%) of the resistant hypertensive and 381 (52%) of the nonresistant hypertensive patients were anatomically eligible for sympathetic RDN. CONCLUSIONS: The vascular anatomical eligibility criteria of the current guidelines are a major limiting factor for the utilization of RDN as a therapeutic option. Development of new devices and/or techniques may significantly increase the number of candidates for these promising therapeutic options.
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Presión Arterial , Desnervación Autonómica/métodos , Ablación por Catéter , Hipertensión/cirugía , Riñón/irrigación sanguínea , Obstrucción de la Arteria Renal/diagnóstico por imagen , Arteria Renal/diagnóstico por imagen , Arteria Renal/inervación , Anciano , Desnervación Autonómica/efectos adversos , Ablación por Catéter/efectos adversos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Prevalencia , Radiografía , Arteria Renal/anomalías , Obstrucción de la Arteria Renal/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Suiza , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND: CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS: In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS: Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS: Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).
Asunto(s)
Mal de Altura/diagnóstico por imagen , Ecocardiografía Doppler , Ecocardiografía de Estrés , Ejercicio Físico , Hipertensión Pulmonar/diagnóstico por imagen , Contracción Miocárdica , Función Ventricular Derecha , Aclimatación , Adulto , Altitud , Mal de Altura/fisiopatología , Presión Arterial , Bolivia , Enfermedad Crónica , Prueba de Esfuerzo , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Circulación Pulmonar , Suiza , Resistencia Vascular , Función Ventricular IzquierdaRESUMEN
Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems.
Asunto(s)
Anomalías Cardiovasculares/etiología , Metilación de ADN , Endotelio Vascular/fisiopatología , Fertilización In Vitro/efectos adversos , Hipertensión/etiología , Longevidad , Animales , Aorta/enzimología , Butiratos/farmacología , Butiratos/uso terapéutico , Anomalías Cardiovasculares/embriología , Dieta Aterogénica , Susceptibilidad a Enfermedades , Regulación hacia Abajo , Endotelio Vascular/embriología , Femenino , Fertilización In Vitro/métodos , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Hipertensión/embriología , Hipertensión/fisiopatología , Masculino , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/fisiología , Inducción de la Ovulación/efectos adversos , Regiones Promotoras Genéticas , Resistencia Vascular/fisiología , Vasodilatación/fisiologíaRESUMEN
The clinical demand for a device to monitor blood pressure (BP) in ambulatory scenarios with minimal use of inflation cuffs is increasing. Based on the so-called pulse wave velocity (PWV) principle, this paper introduces and evaluates a novel concept of BP monitor that can be fully integrated within a chest sensor. After a preliminary calibration, the sensor provides nonocclusive beat-by-beat estimations of mean arterial pressure (MAP) by measuring the pulse transit time (PTT) of arterial pressure pulses travelling from the ascending aorta toward the subcutaneous vasculature of the chest. In a cohort of 15 healthy male subjects, a total of 462 simultaneous readings consisting of reference MAP and chest PTT were acquired. Each subject was recorded at three different days: D, D+3, and D+14. Overall, the implemented protocol induced MAP values to range from 80 ± 6 mmHg in baseline, to 107 ± 9 mmHg during isometric handgrip maneuvers. Agreement between reference and chest-sensor MAP values was tested by using intraclass correlation coefficient (ICC = 0.78) and Bland-Altman analysis (mean error = 0.7 mmHg, standard deviation = 5.1 mmHg). The cumulative percentage of MAP values provided by the chest sensor falling within a range of ±5 mmHg compared to reference MAP readings was of 70%, within ±10 mmHg was of 91%, and within ±15 mmHg was of 98%. These results point at the fact that the chest sensor complies with the British Hypertension Society requirements of Grade A BP monitors, when applied to MAP readings. Grade A performance was maintained even two weeks after having performed the initial subject-dependent calibration. In conclusion, this paper introduces a sensor and a calibration strategy to perform MAP measurements at the chest. The encouraging performance of the presented technique paves the way toward an ambulatory compliant, continuous, and nonocclusive BP monitoring system.