Joaquín Montero

Primary Aldosteronism and Hypertensive Disease

Abstract—Recent studies in hypertensive populations that have used the serum aldosterone (SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a high prevalence of primary aldosteronism (PA). This frequency is higher than that previously described when hypokalemia was used as a screening tool. However, other factors, such as the characteristics of hypertensive disease, could also influence the prevalence of PA. We studied 609 essential hypertensive patients, classified according to the Joint National Committee VI (JNC VI), in 3 different stages depending on the severity of their hypertensive disease. We measured SA and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio >25 was detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA diagnoses in 37 of 609 (6.1%) cases. PA prevalence according to hypertension stage was as follows: stage 1, 6 of 301 cases (1.99%); stage 2, 15 of 187 cases (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger than the other hypertensive patients (48.4±10.5 vs 53.6±10.2 years; P <0.05). Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of PA in essential hypertensives classified in stages 2 and 3 according to the JNC VI. The low frequency of computed tomography scan abnormalities and hypokalemia suggests that the diagnosis for most PA patients corresponds to attenuated forms of the disease.

Biochemical and genetic characterization of 11 beta-hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives.

Background The 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) catalyzes the conversion of cortisol (F) to cortisone (E), avoiding the interaction of cortisol with the mineralocorticoid receptor. If it fails, cortisol will stimulate sodium and water reabsorption, increasing the intravascular volume that suppresses renin and secondarily increase the blood pressure. Objective To look for the possible contribution of a decreased ability of 11βHSD2 to convert cortisol to its inactive metabolite cortisone in the pathogenesis of low renin hypertension (LREH). Patients and methods We studied 64 LREH patients (plasma renin activity, PRA < 1 ng/ml per h), eighty normo-renin essential hypertensives (NREH) (PRA: 1–2.5 ng/ml per h) and 74 normotensives. Serum aldosterone (SA), F, E and serum F/E ratio was determined in all patients. A serum F/E ratio was considered high when it was higher than X + 2SD from the normotensive value. Cytosine-adenine (CA)-repeat microsatellite region in intron 1 of HSD11B2 gene was genotyped in all patients and normotensives volunteers. In 13 LREH with high F/E ratio we performed HSD11B2 gene sequencing. Results LREH had serum F/E ratio higher than NREH and normotensive controls (3.6 (2.9–4.3) versus 2.9 (2.2–4.3) versus 3.0 (2.4–3.7) (P = 0.004), respectively). We observed an inverse relation between F/E ratio and SA and PRA. In NREH and normotensives we did not find correlation between these variables. In the LREH subset the longer 155 bp CA-allele showed the highest serum F/E ratio. No mutations in coding region or short introns were found in LREH patients. Conclusion In this study we show that low-renin essential hypertensives had increased serum cortisol/cortisone ratios as compared with normotensive subjects. This suggest that some essential hypertensives, with suppressed renin activity, may have an impairment in the cortisol inactivation catalyzed by the enzyme 11βHSD2, whose low activity in LREH patients could be associated with the length of CA-repeat microsatellite in intron 1 of the HSD11B2 gene.

T235 variant of the angiotensinogen gene and blood pressure in the Chilean population.

Background The angiotensinogen gene has recently been linked to essential hypertension. A variant within this gene, encoding threonine rather than methionine at amino acid position 235, was associated with essential hypertension. However, results of new studies have not confirmed this association, suggesting that ethnic differences may explain the different results. Objective To evaluate whether the T235 variant is associated with a higher incidence of essential hypertension among Hispanics (a group that has scarcely been evaluated) and to determine whether T235 is associated with variations in the plasma renin activity or the serum aldosterone level. Patients and method We studied 64 patients with essential hypertension and 62 normotensives, matched for age and sex. We obtained samples for determinations of plasma renin activity, serum aldosterone level and genome DNA from all subjects. The genomic DNA was amplified using the polymerase chain reaction technique and digested by the restriction enzyme streptococcus faecalis (Sfa NI) which cuts M235 only, not T235. Results The patients with essential hypertension had a higher prevalence of the risk variant T235 (alleles 77/128 = 60.2%) than did the normotensive controls (alleles 65/124 = 52.4%), but the difference was not statistically significant (χ2 = 1.53, P = 0.22). The plasma renin activity levels in hypertensives were not statistically different for homozygous T235, heterozygous and homozygous M235 (1.0 ± 0.96, 2.0 ± 2.25 and 1.55 ± 1.49 ng/ml per h, respectively, P = 0.5 1). However, when we considered those hypertensives with low plasma renin activity levels (< 1 ng/ml per h), we found a high prevalence (72.7%) of subjects homozygous for the T235 variant. We found no association between the T235 variant and the serum aldosterone levels in hypertensive and normotensive subjects. Conclusions We demonstrated that there is a high prevalence of T235 variant in our Hispanic population. The slight difference between prevalences of T235 variant among hypertensive and normotensive subjects that we found was not statistically significant and did not permit us to establish an association between T235 variant and essential hypertension. We believe that only studying a larger cohort of subjects could show whether there is a quantitative effect of the T allele on plasma renin activity levels.

Competencias médicas requeridas para el buen desempeño en Centros de Salud Familiares en Chile

A group ofexperts that could be physicians or other professionals working in primary health care wereinvited to answer electronically a structured questionnaire containing a list of 71 competences,for a basic and an expert level of physician, using the Delphi method. Competences wereclassified as “desirable” or “indispensable”. If there was lack of consensus in the importancegiven to a specific competence, the researchers defined its importance.

Metodología para la evaluación de la relación costo-efectividad en centros de atención primaria de Chile

OBJETIVO: Presentar una metodologia para la evaluacion de la relacion costo-efectividad en centros de atencion primaria de salud (APS) a partir del modelo de atencion familiar promovido en Chile y evaluar los resultados de los dos primeros anos de funcionamiento del primer centro piloto que funciona bajo este nuevo modelo de atencion primaria. METODOS. Se realizo un estudio de costo-efectividad, con una perspectiva social y un horizonte temporal de un ano. Para comparar el centro intervenido (universitario) con el centro de control (municipal) se construyo el indice compuesto de calidad de los centros de salud familiar (ICCESFAM), que combina indicadores tecnicos y la percepcion de los usuarios de los centros en seis dimensiones: accesibilidad, continuidad de la atencion medica, enfoque clinico preventivo y promocional, resolutividad, participacion, y enfoque biopsicosocial y familiar. Para calcular los costos se tomo en cuenta el gasto en los centros, el ahorro producido al resto del sistema sanitario y el gasto de bolsillo de los pacientes. Se estimo la razon costo-efectividad incremental (RCEI) y se realizo un analisis de sensibilidad. RESULTADOS: El centro de salud universitario resulto 13,4% mas caro (US

La preocupante falta de formación en desastres dentro de las escuelas de medicina latinoamericanas

8,93 anuales adicionales por inscrito) y mas efectivo (ICCESFAM 13,3% mayor) que el municipal. Estos resultados hacen que la RCEI sea de US

Efecto de la incorporación de registros adicionales a la presión arterial en la Encuesta Nacional de Salud, Chile 2010

0,67 por cada punto porcentual adicional que aumenta el ICCESFAM. CONCLUSIONES: Segun el modelo elaborado de evaluacion de centros de APS, los centros que siguen el modelo de salud familiar chileno son mas efectivos, tanto por sus indicadores tecnicos como por la valoracion de sus usuarios, que los centros de APS tradicionales.

Primary hyperaldosteronism in essential hypertensives : Prevalence, biochemical profile, and molecular biology

De acuerdo al Centro de Investigacion sobre laEpidemiologia de los Desastres, entre 1974 y 2003 ocu-rrieron 6 367 desastres en el mundo, sin contar las epi-demias. Estos desastres han dejado un saldo de mas de2 millones de muertos, 5 100 millones de afectados,182 millones de personas sin hogar y danos en infraes-tructura valuados en US

Two Homozygous Mutations in the 11β-Hydroxysteroid Dehydrogenase Type 2 Gene in a Case of Apparent Mineralocorticoid Excess

1,38 billones (1). Solo en el presente ano, dos devastadores terre-motos asolaron a nuestro continente, uno el 12 deenero en Haiti, que dejo un saldo aproximado de 230 000 muertes, 300 000 lesionados y 1 000 000 de per-sonas sin hogar, y otro el 28 de febrero en Chile, dondese notificaron 342 victimas fatales, 97 desaparecidos,800 000 damnificados y perdidas materiales por unosUS

Genetic Study of Patients with Dexamethasone-Suppressible Aldosteronism without the Chimeric CYP11B1/CYP11B2 Gene

29 662 millones (2, 3). En 2005, el huracan Katrinadejo a su paso una ciudad practicamente destruida porlas inundaciones, mas de 1 800 personas muertas ycerca de 146 000 sin hogar, y danos materiales por US