Inflamación y aterotrombosis. Precocidad de la lesión vascular. Opciones diagnósticas y terapéuticas para prevención primaria / No disponible

La aterosclerosis, una enfermedad inflamatoria, se desarrolla precozmente en la ERC (Fuerza de Recomendación B). Por ello se plantea la indicación de la realización de pruebas para el diagnóstico de aterosclerosis subclínica y de inflamación sistémica.• Los pacientes con ERC tienen un alto riesgo vascular, lo que implica un tratamiento por objetivos de los factores de riesgo vascular.• En este contexto, se puede considerar la realización de pruebas de imagen para el diagnóstico de aterosclerosis subclínica a fin de individualizar las decisiones terapéuticas sobre el manejo de los factores de riesgo cardiovascular cuando el paciente no esté recibiendo ya un tratamiento consistente con el máximo nivel de riesgo (..) (AU)

Atherosclerosis, an inflammatory disease, develops prematurely in CKD (Strength of Recommendation B). The performance of tests for the diagnosis of subclinical atherosclerosis and systemic inflammation should therefore be considered in these patients.• Patients with CKD are at high risk of vascular disease, implying the need for goal-based treatment of the vascular riskfactors.• In this context, imaging tests for the diagnosis of subclinical atherosclerosis can be considered with the goal of individualizing treatment decisions on the management of cardiovascular risk factors when the patient is no longer receiving treatment consistent with the maximum risk level (..) (AU)

Hipertensión arterial y dislipemia en el paciente con enfermedad renal crónica (ERC). Antiagregación.Terapéutica por objetivos / No disponible

TRATAMIENTO DE LA HIPERTENSIÓN ARTERIAL• La presión arterial (PA) debe medirse periódicamente en todos los pacientes con ERC (Fuerza de Recomendación C).• El control de la PA y la reducción de la proteinuria retrasan la progresión de la ERC (Fuerza de Recomendación A) y reducen el riesgo cardiovascular (Fuerza de Recomendación C), por lo que el objetivo del tratamiento debe ser el control de ambos factores.• El objetivo de PA en los pacientes con ERC debe ser< 130/80 mmHg y 125/75 mmHg si la proteinuria es > 1g/24 horas (Fuerza de Recomendación A).• Deben adoptarse modificaciones en el estilo de vida: dieta baja en sodio (menos de 100 mEq/día de sodio o 2,4 g/día de sal), reducción ponderal si existe sobrepeso(índice de masa corporal 20-25 kg/m2), ejercicio físico aeróbico regular e ingesta moderada de alcohol, para el control de la PA y prevención del riesgo cardiovascular (Fuerza de Recomendación A).• La elección del fármaco antihipertensivo en los pacientes con IRC depende de la etiología de la misma, del riesgo cardio vascular o presencia de enfermedad cardiovascular clínica o subclínica (Fuerza de Recomendación A).• Generalmente se precisan 2 o más fármacos antihipertensivos para controlar la presión arterial en pacientes con IRC (Fuerza de Recomendación B) que frecuentemente incluirá un diurético, que en estadios 4-5 debe (..) (AU)

TREATMENT OF ARTERIAL HYPERTENSION• Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C).• BP control and proteinuria reduction delay progression of CKD(Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective.• The BP target in patients with CKD should be < 130/80mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours(Strength of Recommendation A).• Lifestyle changes should be made: low-sodium diet (less than100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A).• The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A).• Two or more antihypertensive drugs are usually required to (..) (AU)

[Inflammation and atherothrombosis. Premature vascular injury. Diagnostic and therapeutic options for primary prevention]. / Inflamación y aterotrombosis. Precocidad de la lesión vascular. Opciones diagnósticas y terapéuticas para prevención primaria.

Atherosclerosis, an inflammatory disease, develops prematurely in CKD (Strength of Recommendation B). The performance of tests for the diagnosis of subclinical atherosclerosis and systemic inflammation should therefore be considered in these patients. - Patients with CKD are at high risk of vascular disease, implying the need for goal-based treatment of the vascular risk factors. - In this context, imaging tests for the diagnosis of subclinical atherosclerosis can be considered with the goal of individualizing treatment decisions on the management of cardiovascular risk factors when the patient is no longer receiving treatment consistent with the maximum risk level (Strength of Recommendation C). - The presence of subclinical atherosclerosis would raise cardiovascular risk to the maximum level (Strength of Recommendation C). - Carotid artery ultrasound with determination of carotid intima- media thickness (CIMT) and the presence of atheromatous plaques would be the technique of choice for the assessment of subclinical atherosclerosis in ACKD (Strength of Recommendation C). - C-reactive protein, measured by high-sensitivity assay (hs-CRP), is the only marker of inflammation used routinely in clinical practice. However, there is no evidence that routine determination of hs-CRP improves the outcomes of therapeutic decisions on cardiovascular protection in either the general population or ACKD population. Therefore, routine CRP determination cannot be recommended in patients with CKD to stratify their cardiovascular risk (Strength of Recommendation C).

[Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment]. / Hipertension arterial y dislipemia en el paciente con enfermedad renal cronica (ERC). Antiagregacion. Terapeutica por objetivos.

TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricular hypertrophy (LVH) is a cardiovascular risk factor in patients with CRF (Strength of Recommendation B). - It is advisable to perform an echocardiogram at baseline and every 12-24 months and to consider treatments allowing for LVH regression (Strength of Recommendation C). The approach to LVH should be early and multifactorial because its reversibility is limited once established (Strength of Recommendation C). - RAAS blockade with ACEIs or ARBs partially reverts LVH in patients with CRF (Strength of Recommendation B). ANTI-PLATELET AGGREGATION - Because of the high cardiovascular risk in patients with CKD, anti-platelet aggregant therapy, especially low-dose aspirin, would be indicated in patients with type 2 diabetes as primary prevention, and in all patients with CKD as secondary prevention. There is however no evidence of the benefits of anti-platelet aggregant therapy in primary prevention in patients with CKD, particularly in stages 4-5; indication for treatment in this situation should therefore be individualised because of its greater risk of bleeding. - Adequate good blood pressure control should previously be achieved to minimise the risk of haemorrhagic stroke (Strength of Recommendation C).

Morbimortalidad cardiovascular en la diabetes mellitus tipo 2 / Cardiovascular morbidity and mortality in type 2 diabetes mellitus

No disponible

Hipermineralocorticismo exógeno como causa de descompensación de una hipertensión esencial previamente controlada / Exogenous hypermineralocosticism as a acaue of aggravation of a previusly well-controlled hypertension

Una de las causas reconocidas de hipertensión arterial secundaria son los estados de hipermineralcorticismo. Presentamos el caso de un paciente hipertenso conocido desde hacía 8 años, bien controlado con tratamiento farmacológico, que a raíz de un emporamiento de las cifras tensionales y una hipocaliemia de novo se diagnosticó un hipermineralocorticismo exógeno por ingesta de regaliz. Se trataba de un hombre de 50 años que estaba diagnosticado de hipertensión esencial que presentaba un buen control desde hacia 8 años con tratamiento combinado de antagonistas de los canales de calcio y betabloqueantes. En los 6 meses previos se asistió a una dificultad en el control tensional e hipocaliemia. Los estudios posteriores descartaron un hiperaldosteronismo y un síndrome de Cushing, por lo que tras un extenso reinterrogatorio se constató la ingesta de regaliz, que coincidía en el tiempo con la elevación de la presión arterial. Tras la supresión de la ingesta de regaliz se logró de nuevo un correcto control de la presión. En el screening del paciente hipertenso no debe olvidarse la existencia de causas exógenas de hipertensión, que pueden ser causa de la misma o agravante, como en el caso que nos ocupa, de una hipertensión previamente controlada (AU)

Mecanismos de desarrollo del daño vascular en pacientes en diálisis / Mechanisms of development of vascular disease in dialysis patients

Los pacientes en diálisis tienen una tasa de mortalidad ajustada para la edad de 3,5-4 veces superior a la de la población general. La patología cardiovascular es la principal causa de muerte en estos pacientes. Los registros de pacientes en tratamiento sustitutivo renal en distintas poblaciones (EE.UU, Europa, Australia o Japón) coinciden en indicar que alrededor del 50 por ciento de las muertes son debidas a complicaciones cardiovasculares1-7. En una era en la que la mortalidad cardiovascular disminuye en la población general en el mundo occidental no se ha observado Mechanisms of development of vascular disease in dialysis patients Los pacientes en diálisis constituyen un grupo de alto riesgo cardiovascular, ya que esta patología representa alrededor del 50 por ciento de las causas de muerte en estos pacientes y la mortalidad cardiovascular es entre 10 y 20 veces superior en estos pacientes respecto a la población general tras estratificación por edad, sexo y raza.La patología cardiovascular se asocia con un remodelado vascular complejo que incluye afectación macrovascular en forma de aterosclerosis y arterioesclerosis, así como disfunción endotelial y afectación de la microvasculatura. Estos pacientes representan una mayor prevalencia de lesiones ateroscleróticas que la población general y éstas están frecuentemente calcificadas. Además presentan una mayor prevalencia de arterioesclerosis de grandes arterias, lo que comporta un aumento de la rigidez arterial. Las consecuencias de esta rigidez arterial son la hipertrofia ventricular izquierda, el agravamiento de la isquemia coronaria y un aumento de la fatiga de la pared vascular arterial. Estos pacientes presentan también una disfunción endotelial y una alteración de la microvasculatura caracterizada por un engrosamiento arteriolar y una disminución de la densidad capilar cardíaca. Los factores implicados en estos cambios incluyen los factores de riesgo cardiovascular clásicos (edad, hipertensión, diabetes, hiperlipidemia, etc.), así como los nuevos factores de riesgo cardiovascular (hiperhomocisteinemia, hiperfibrinogenemia, lipoproteína(a), estrés oxidativo, etc.) muy frecuentes en estos pacientes, así como factores propios de la uremia (anemia, alteraciones del metabolismo calcio-fósforo, hiperparatiroidismo, etc.). Por todo ello estos pacientes deben ser considerados como un grupo de alto riesgo cardiovascular y por tanto el tratamiento de los factores de riesgo cardiovascular debe ser agresivo y multifactorial para intentar reducir la elevada morbimortalidad cardiovascular que presentan (AU)

Papel de la adrenomedulina en el control de la presión arterial y la homeostasis del líquido extracelular

La adrenomedulina es un péptido de 52 aminoácidos recientemente identificado que presenta un efecto vasodilatador potente y prolongado, así como una acción diurética y natriurética a nivel renal. El efecto vasodilatador de la adrenomedulina está mediado por un aumento de los niveles intracelulares de AMP cíclico, así como por un aumento de la síntesis de óxido nítrico. Los efectos diurético y natriurético de este péptido son debidos tanto a sus acciones sobre el flujo sanguíneo renal como sobre la función tubular. Además, la adrenomedulina inhibe la secreción de aldosterona estimulada por angiotensina, tiene un efecto inotrópico positivo sobre el miocardiocito, inhibe la proliferación y migración de la fibra muscular lisa vascular, y a nivel cerebral inhibe la sed y el apetito por la sal. La expresión de este péptido se ha demostrado en muchos tejidos, pero es especialmente prominente en células endoteliales. Por ello se cree que la producción de este péptido en las células endoteliales, regulada por el estrés de cizallamiento (flujo), citoquinas o neurohormonas, actúa de forma paracrina en la fibra muscular lisa subyacente causando vasodilatación. Los niveles plasmáticos de adrenomedulina están elevados en la hipertensión arterial, insuficiencia cardíaca, infarto de miocardio, insuficiencia renal, diabetes complicada, así como en el shock séptico. Los efectos biológicos de adrenomedulina, así como la demostración de niveles plasmáticos elevados del mismo en diversas patologías cardiovasculares y renales parecen confirmar su papel en la regulación de la presión arterial y del equilibrio hidroelectrolítico, aunque todavía son necesarios más estudios para dilucidar su papel fisiopatológico en las enfermedades cardiovasculares (AU)

Autonomic nervous system and adrenergic receptors in chronic hypotensive haemodialysis patients.

BACKGROUND: The pathophysiology of chronic hypotension (CH) in uraemia is not elucidated. The possible role of autonomic nervous system dysfunction and adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in this study. METHODS: Seventeen hypotensive haemodialysis (HD) patients, 17 normotensive HD patients, and 17 control subjects were studied. We evaluated the integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic efferent pathway ('deep-breathing test') and the sympathetic efferent pathway ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2-adrenoceptor response (intracellular cAMP generation after isoproterenol stimulation in lymphocytes). RESULTS: Responses to the Valsalva manoeuvre and the deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio was lower in hypotensive patients than in normotensive patients (P < 0.01), whereas the pressor response to the hand-grip test was reduced only in hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood pressure (MBP) correlated with MBP increases during the hand-grip exercise (r = 0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD patients than in normotensive patients (P < 0.05). alpha 2- and beta 2-adrenoceptor densities and beta 2-adrenoceptor response were reduced in hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P < 0.025) densities in HD patients. CONCLUSIONS: Normotensive haemodialysed patients have increased plasma catecholamine levels with preserved alpha 2- and beta 2-adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive patients, plasma adrenaline levels were even higher; the increased plasma catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation. This downregulation may play a role in the reduced cardiovascular responses to adrenergic stimuli reported in hypotensive HD patients.

New insights into the pathophysiology of renovascular hypertension.

In recent years, the pathophysiology of renovascular hypertension has been reviewed, and the classic concept that activation of the renin-angiotensin system is solely responsible for the development and maintenance of renovascular hypertension has been challenged. In fact, experimental evidence indicates that other systems, such as the lipoxygenase pathway, may have a more critical role in the long-term maintenance of high blood pressure after renal artery stenosis. Herein we discuss the intrarenal mechanisms that control pressure-induced natriuresis under physiologic conditions and the role of the kidney in the pathophysiology of renovascular hypertension.

Vasoactive hormones in uraemic patients with chronic hypotension.

BACKGROUND: We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia. METHODS: Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured. RESULTS: The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01). CONCLUSIONS: Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.

[Autonomic dysfunction in chronic hypotension associated with uremia]. / Disfunción autonómica en la hipotensión crónica asociada a la uremia.

BACKGROUND: Chronic hypotension is a not uncommon complication among hemodialyzed patients which is responsible of an important morbidity. The autonomic nervous system (ANS) dysfunction seems to play a key role in the pathogenesis of chronic hypotension. METHODS: In order to study whether ANS dysfunction is responsible for chronic hypotension in hemodialyzed patients, the authors evaluated the integrity of the whole baroreflex arc by the Valsalva's manoeuver, of parasympathetic efferent pathway by the deep-breathing test and of sympathetic efferent pathway by the hand-grip test in 16 hemodialyzed patients with chronic hypotension, 17 normotensive hemodialyzed patients and 17 normal control subjects. Plasma catecholamine levels were also measured in these patients. RESULTS: In normotensive patients, Valsalva's manoeuver response (p < 0.005) and deep-breathing test response (p < 0.05) were lowered, while hand-grip test response was preserved. In chronic hypotensive patients, in addition to an impaired deep-breathing test (p < 0.05), a further reduced Valsalva's manoeuver response and a lower pressor response to hand-grip test were observed (p < 0.001). Catecholamine levels were higher in both groups of patients (p < 0.01) with respect to control subjects, specially in chronic hypotensive patients. CONCLUSIONS: In hemodialyzed patients (both normotensive and hypotensive) the whole baroreflex function and parasympathetic response are impaired. The lower pressor response to hand-grip test observed in hypotensive patients, in spite of the higher catecholamine levels, suggest that in these patients the cardiovascular dysfunction cannot be ascribed to a reduced sympathetic "outflow" but to a resistance of the target organs (heart and vessels) to the sympathetic stimulation.

[Vascular hyperreactivity to vasopressin in mild essential arterial hypertension]. / Hiperreactividad vascular a la vasopresina en la hipertensión arterial esencial moderada.

The aim of the present study was to evaluate the hemodynamic effects of arginine vasopressin (AVP) infusion in essential hypertension. To this end, 9 hypertensive patients and 10 normotensive controls were evaluated. After one hour rest, AVP was infused at a dosage of 0.5 and 2 ng/(kg/min), in 20 minutes periods. After AVP infusion, mean arterial pressure increased only in hypertensive patients (from 125.8 +/- 7 to 131.8 +/- 7, p less than 0.01 and to 135.6 +/- 6 mmHg, p less than 0.01). Peripheral vascular resistance was significantly increased in both groups during AVP infusion, although the percent increase was higher in hypertensive patients during the last period of infusion (18.3 +/- 10 versus 4.6 +/- 4, p less than 0.05). Cardiac index decreased in both groups during infusion, although this reduction was significantly higher in hypertensive patients than in healthy controls in the last period of infusion (-8.16 +/- 6 versus -1.8 +/- 4%, p less than 0.05). These results confirm that in essential hypertension there is an exaggerated pressor response to AVP infusion, suggesting that it is due to an increased vascular response to this hormone. The compensatory reduction of cardiac output and the inhibition of sympathetic nervous activity mediated through baroreceptor reflexes do not apparently play a role in this pressor response.