Aportación del proyecto CARDIORISC al manejo del paciente hipertenso de Atención Primaria en España / Contribution of the CARDIORISC project to the management of hypertensive patients in Primary Health Care in Spain

El proyecto CARDIORISC es una iniciativa de la Sociedad Española de Hipertensión (SEH-LELHA), avalado por la Sociedad Europea de Hipertensión (ESH), iniciado en el año 2004 y que tiene como objetivo general optimizar la asistencia al paciente hipertenso en España. Comprende los registros MAPAPRES que pretende introducir la monitorización ambulatoria de la presión arterial (MAPA) como herramienta rutinaria en la valoración del paciente hipertenso en la práctica clínica en España, el registro AMPAPRES que evaluará el grado de control de la hipertensión arterial (HTA) mediante la automedida de la presión arterial (AMPA) por parte del paciente y el registro piloto FAPRES que evaluará la prevalencia de fibrilación auricular en la población hipertensa en la Comunidad Valenciana. El registro MAPAPRES está generando numerosas evidencias basadas en el análisis de la base de datos de más de 60.000 pacientes, aportadas por más de 1.000 investigadores, que se han incluido hasta la fecha. Se presentan, de manera resumida, en esta publicación algunas de las líneas de investigación más relevantes para la práctica clínica diaria del médico de Atención Primaria

The CARDIORISC project is an initiative of the Spanish Society of Hypertension (SEH-LELHA), endorsed by the European Society of Hypertension (ESH). It was established in the year 2004 and its general purpose is to improve care to the hypertensive patient in Spain. It includes the MAPAPRES registry that aim to introduce ambulatory blood pressure monitoring (ABPM) as a routine tool in the assessment of the hypertensive patient in the clinical practice in Spain, the AMPAPRES registry that will evaluate the control rate of arterial hypertension (AHT) using the self-measurement of blood pressure (SMBP) by the patient and the pilot registry FAPRES that will evaluate the prevalence of atrial fibrillation in the hypertensive population in the Spanish Valencian Community. The MAPAPRES registry is generating a great deal of evidence based on the analysis of the database of more than 60,000 patients provided by more than 1000 investigators. A summary of some of the most relevant lines of research for the daily clinical practice of the Primary Health Care physician are presented in this publication

Repercusiones orgánicas de la hipertensión arterial: vasos, cerebro, corazón y riñón / Organic repercussions of the arterial hypertension: vessels, brain, heart and kidney

En la hipertensión arterial (HTA) existe alteración hemodinámica y cambios humorales que afectan a la morfología y a la función de la pared arterial. La pared vascular se modifica en todas sus capas dando lugar a lo que se denomina enfermedad vascular hipertensiva, que se traduce clínicamente en arteriosclerosis y sus consecuencias: isquemia miocárdica, accidente cerebrovascular e insuficiencia renal como manifestaciones directas de mayor relevancia clínica. El endotelio vascular normal proporciona un entorno antiaterogénico, pero cuando se altera se producen modificaciones fenotípicas de las células endoteliales que propician un ambiente vasoespástico, protrombótico y proinflamatorio. En el cerebro, la HTA multiplica por 6 el riesgo de sufrir un ictus, de forma que se estima que el 50 % de los infartos isquémicos o hemorrágicos tienen como base la HTA. Además, la segunda clase en frecuencia de demencia, la vascular, tiene una estrecha correlación con la HTA. En el corazón, la HTA produce 3 patologías diferenciadas: hipertrofia ventricular izquierda (HVI), cardiopatía isquémica (CI) e insuficiencia cardíaca. El riesgo de CI es 3,5 veces mayor y el de muerte súbita 4,5 veces mayor en pacientes con HVI que en su ausencia, considerándose un factor de riesgo independiente para todas las complicaciones cardiovasculares. En el riñón, la HTA produce nefroangioesclerosis, que se inicia por vasoconstricción de la arteriola aferente, que es dependiente de angiotensina II y/o actividad simpática. La influencia de la presión arterial sobre la filtración glomerular es de tal calibre que en pacientes con nefropatía y proteinuria mayor de 1 g se recomienda que el control de la presión arterial debe llegar a cifras inferiores a 125/75 mmHg

In arterial hypertension (AHT), there are hemodynamic alterations and humoral changes that affect the morphology and function of the arterial wall. The vascular wall is modified in all its layers, giving rise to what is called hypertensive vascular disease. This is clinically interpreted as arteriosclerosis and its consequences: myocardial ischemia, cerebrovascular accident and renal failure as direct manifestations of greatest clinical relevance. The normal vascular endothelium provides an antiatherogenic setting. When it is altered, phenotypic changes of the endothelial cells are produced. This favors a prothrombotic and proinflammatory vasospastic state. In the brain, AHT multiplies the risk of suffering a stroke six fold, it being estimated that the bases of 50 % of ischemic infarction or hemorrhaging is AHT. Furthermore, the second class in frequency of dementia, the vascular one, has a close correlation to AHT. In the heart, AHT produces three differentiated diseases: left ventricular hypertrophic (LVH), ischemic heart disease (IHD), and heart failure. The risk of IHD is 3.5 times greater than that and of sudden death 4.5 times greater in patients with LVH than in those without it, it being considered an independent risk factor for all of the cardiovascular complications. On the renal level, AHT produces nephroangiosclerosis that is initiated by vasoconstriction of the afferent arteriole which is dependant on angiotensin II and/or sympathetic activity. The influence of the blood pressure on glomerular filtration is of such caliber that it is recommended that blood pressure control should achieve values under 125/75 mmHg in patients who have a nephropathy and proteinuria over 1 g

Eficacia y tolerabilidad de irbesartán en pacientes con hipertensión arterial y diabetes mellitus tipo 2 / Effectiveness and tolerability of irbesartan in patients with arterial hypertension and type 2 diabetes mellitus

Fundamento. La coexistencia de hipertensión arterial (HTA) y diabetes tipo 2 constituye una combinación de incidencia creciente y de elevado riesgo cardiovascular. El bloqueo del sistema renina angiotensina con inhibidores de la enzima convertidora (IECA) o con antagonistas de los receptores de angiotensina confiere a los pacientes con HTA y diabetes una mayor protección frente a la enfermedad cardiovascular (ECV) y renal (ER). El presente estudio tiene como objetivo evaluar la eficacia y la tolerabilidad del antagonista de los receptores de angiotensina irbesartán en una cohorte de pacientes con HTA y diabetes mellitus tipo 2.Diseño y métodos. Estudio prospectivo observacional en una cohorte de 1.184 pacientes diagnosticados de diabetes mellitus tipo 2, con cifras de tensión arterial (TA)>= 130 y/o 85 mmHg. El tratamiento antihipertensivo se realizó con irbesartán a dosis entre 75 y 300 mg añadiendo posteriormente hidroclorotiazida 12,5 mg/día si no se había alcanzado el objetivo de reducir la TA a un nivel inferior a 130/85 mmHg. El seguimiento clínico fue de 12 semanas. La eficacia del fármaco se evaluó mediante la disminución de la TA determinada por un sistema de medida oscilométrico semiautomático. Las variables de seguridad fueron los niveles de creatinina y de potasio séricos, así como la aparición de reacciones adversas. Resultados. El tratamiento con irbesartán produjo un descenso significativo (p = 0,0001), tanto de la TA sistólica (TAS) (de 157,6 ñ 17,1 a 141,8 ñ 18,8 mmHg) como de la TA diastólica (TAD) (de 90,5 ñ 10,2 a 81,0 ñ 9,9 mmHg). El porcentaje de pacientes controlados a las 12 semanas fue del 70,4 por ciento para la TAD (< 85 mmHg) y del 17 por ciento para la TAS (< 130 mmHg). No se verificaron cambios significativos en los valores medios de creatinina (de 0,97 ñ 0,19 a 0,98 ñ 0,19 mg/dl) ni en las cifras de potasio sérico (de 4,34 ñ 0,46 a 4,34 ñ 0,48 mmol/l). Igualmente, la tasa de reacciones adversas fue mínima, pues sólo el 3,1 por ciento de los pacientes presentaron alguna reacción adversa. Conclusiones. El irbesartán es un fármaco eficaz, seguro y bien tolerado para el tratamiento de la HTA en pacientes con diabetes tipo 2. Produce descensos significativos de la TA con una tasa muy baja de reacciones adversas (AU)

Both alleles of the M235T polymorphism of the angiotensinogen gene can be a risk factor for myocardial infarction.

We have studied the role of three polymorphic genes of the renin-angiotensin system (RAS) as independent risk factors for myocardial infarction (MI) and their correlation with three of the major coronary risk factors: serum cholesterol (CH), hypertension (HT) and smoking (SM). A population of 392 men was genotyped for the M235T polymorphism of the angiotensinogen (AGT) gene, the insertion/deletion of the angiotensin-converting enzyme (ACE) and the all66c of the angiotensin-II type 1 receptor (AT1R), by means of polymerase chain reaction (PCR) and restriction enzyme analysis. It was observed that the T allele frequency increased significantly in the MI with HT, CH, and SM subgroup (0.58 vs 0.31) (p<0.01). In contrast, the M allele frequency was higher in the MI without HT, CH, and SM (0.69 vs 0.42) (p<0.01). A strong association between the MM genotype and MI (p<0.001, odds ratio=4.29, confidence interval=1.95-9.42) was found when age-matched MM control subjects were compared to MI individuals with none of the other known major coronary risk factors. Futhermore, subjects with the MM genotype showed a significantly higher plasma renin activity (PRA) profile than those with the TT genotype (p<0.001). It can be concluded that the M allele is an independent risk factor for MI and the T allele modified the risk when other major risk factors are present.

Hipertensión e hipercolesterolemia en la población española

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The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction.

We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted.

[Diastolic dysfunction, left ventricular hypertrophy, and microalbuminuria in mild to moderate essential arterial hypertension]. / Disfunción diastólica, hipertrofia ventricular izquierda y microalbuminuria en la hipertensión arterial esencial ligera-moderada.

INTRODUCTION: It is known, that there is a high prevalence of left ventricular diastolic disfunction, which precedes left ventricular hypertrophy in hypertensive people, but there is little published in literature about the relationship between these findings and the presence of microalbuminuria. OBJECTIVE: In our study, we pretend to evaluate prevalence and eventual relation among microalbuminuria, diastolic disfunction and left ventricular hypertrophy, in young mild to moderate hypertensive patients, non diabetic and without previous treatment. MATERIAL AND METHODS: We studied prospectively 80 untreated hypertensive patients, with normal serum creatinine, and non diabetic (52.5% women and 47.5% men, mean age 41.4 +/- 9.6 years). We evaluated filling indexes by Doppler Echocardiography: Ratio of early to late diastolic peak filling velocity and early filling deceleration time. Left ventricular hypertrophy was defined by Devereux's criteria. Microalbuminuria in twenty four hours was measured by radioimmunoassay in hypertensive patients (microalbuminuria: 30-300 mg/24 hours). RESULTS: Microalbuminuria occurred in 23.7%, left ventricular hypertrophy 40%, and diastolic disfunction 48.8%, no significant correlation existed between the same. Only 29.5% had no cardiac or renal disease. Statistically significant differences were found in ratio of early to late diastolic peak filling velocity and microalbuminuria, between the two study populations, but multiple regression analysis didn't prove such correlation. Ratio of early to late diastolic peak filling velocity was independently related to age and diastolic blood pressure. CONCLUSIONS: There is a high prevalence of cardiac and/or renal disease in mild hypertensive patients, only 29.5% of these patients are free of disease. We don't find relation between lesions in these organs.

[Hypertensive patients treated in Spain, 1990-1993]. / Estudio sobre los enfermos hipertensos en tratamiento en España durante el período 1990-1993.

BACKGROUND: The main goal of our work was to gain knowledge from the pharmaco-epidemiological perspective on the use of anti-hypertensive drugs in our country, in order to obtain a rough estimation of the number of hypertensive patients under treatment in various Autonomous Communities. METHODS: The data regarding the consumption of hypertensive drugs (mono-medicines) from 1990 to 1993 have been obtained from the Vice-Directorate General for Treatment and Pharmaceutical Planning. The methodology used to calculate the "Estimated Prevalence Patient-day" under treatment with these drugs is based on the WHO recommendations for the Studies on the use of Medicines. Estimated Prevalence of Patient-day (EPPD) has been calculated by using the Defined Daily Dosage of each anti-hypertensive drug. RESULTS: The number of hypertensive patients under treatment with these drugs was 1.763.937, 1.966.396, 2.226.225 and 2.435.294, from 1990 to 1993, respectively. At the end of our study, in 1993, the number of hypertensive patients under treatment in Spain is nearly 50% of the total number of hypertensive patients. There are some differences amongst regions; thus, the Autonomous Communities of Aragón, Castilla-La Mancha, Cataluña, País Valenciano and Murcia are noticeable as regions where the number of hypertensive patients treated exceeds the national average. CONCLUSIONS: The number of hypertensive patients under treatment has considerably increased between 1990 to 1993 (+ 40%). An increase is observed in the number of hypertensive patients treated with calcium antagonists and ECA inhibitors and a decrease is observed in the proportion of hypertensive patients under treatment with Beta-blockers and diuretics.

Angiotensin I-converting enzyme genotypes and angiotensin II receptors. Response to therapy.

In the present study, we studied angiotensin II type 1 (AT1) and type 2 (AT2) receptor messengers by quantitative reverse transcriptase-polymerase chain reaction. We examined peripheral blood mononuclear cells from 30 healthy subjects and 50 subjects with primary hypertension, in whom angiotensin I-converting enzyme genotype was determined, before and after 15 days of treatment with different antihypertensive drugs. The medication included a calcium channel antagonist, an angiotensin I-converting enzyme inhibitor, and a beta 1-blocker. We also studied the relationship between AT1 receptor gene expression and biochemical parameters of the renin-angiotensin system. AT1 receptor messenger levels were positively correlated with plasma renin activity in both normotensive and untreated hypertensive subjects. Increases of this messenger and plasma angiotensin II levels were correlated with the D allele in the same individuals. AT1 receptor messenger levels decreased significantly with angiotensin I-converting enzyme inhibitor treatment in subjects with the DD genotype, and a significant decrease was observed in subjects with the II and ID genotypes treated with a calcium antagonist. No changes were observed in mRNA with the beta 1-blocker. We conclude that the AT2 receptor is not expressed in peripheral leukocytes and that AT1 receptor messenger levels vary in relation to angiotensin I-converting enzyme genotype and pharmacological treatment. These results suggest that angiotensin I-converting enzyme genotype may be an important factor when deciding on antihypertensive therapy in individuals with primary hypertension.

Antihypertensive activity of verapamil: impact of dietary sodium. The VERSAL Study Group.

OBJECTIVE: To define the influence of dietary salt intake on the antihypertensive effect of slow-release verapamil 240 mg once a day in a population with mild-to-moderate essential hypertension. DESIGN: Parallel, randomized, multicentre study. METHODS: Patients were advised to follow a moderately low salt diet (Low-salt group). After a 2-week run-in period, those patients with 24-h urinary sodium excretion (UNa) < or = 120 mmol/day and a diastolic blood pressure (DBP) between 90 and 114 mmHg were randomly assigned to verapamil + Low-salt or verapamil + unrestricted-salt diet (High-salt group) for 28 days. Compliance with diets was defined as Low-salt UNa < or = 120 mmol/day and High-salt UNa > 120 mmol/day with UNa increased by > or = 60 mmol/day over the level attained at the end of the run-in period. RESULTS: Significant reductions in mean systolic blood pressure (SBP) and DBP were found in both the Low-salt (n = 235) and High-salt (n = 183) groups. The therapeutic goal (DBP < 90 mmHg) was achieved in 38.3% of patients in the Low-salt and 44.8% of patients in the High-salt group. Office blood pressure results were confirmed by ambulatory 24-h blood pressure monitoring in a subsample of patients. Verapamil reduced mean blood pressure throughout the nycthemeral cycle without any significant difference between the two groups. CONCLUSION: The restriction in sodium intake does not have an additive effect on the antihypertensive effect of the slow-channel calcium antagonist verapamil.