Estatinas: Características y Efectos sobre el Control Lipídico en el Niño y Adolescente Obeso

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Abstract

La obesidad en niños y adolescentes representa un problema emergente de salud pública, siendo el trastorno nutricional y metabólico más prevalente en los países desarrollados. Paralelo a este incremento de obesidad, han hecho su aparición dislipemias a edades cada vez más tempranas. En la última década se han producido novedosos avances en el tratamiento de estas alteraciones lipídicas, fundamentalmente debido a la introducción de las estatinas en su terapia. Su utilidad y eficacia ampliamente demostrada en adultos parece ser igualmente aplicable en el tratamiento de las hipercolesterolemias durante la infancia. En la actualidad son seis ya las estatinas utilizadas en población infantil, habiendo sido analizada su actividad en niños y jóvenes a través de ensayos clínicos, en los que se concluye su eficacia y seguridad para reducir las concentraciones tanto de colesterol total como de colesterol en lipoproteínas de baja densidad (c-LDL) en sangre. El objetivo de este trabajo ha sido ofrecer una revisión actualizada sobre las características de éstas y sus efectos en la mejora clínica de los niveles de lípidos en sangre en niños y adolescentes con sobrepeso y obesidad.

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Most cited references 69

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Structural mechanism for statin inhibition of HMG-CoA reductase.

E Istvan, J. Deisenhofer (2001)

HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGR) catalyzes the committed step in cholesterol biosynthesis. Statins are HMGR inhibitors with inhibition constant values in the nanomolar range that effectively lower serum cholesterol levels and are widely prescribed in the treatment of hypercholesterolemia. We have determined structures of the catalytic portion of human HMGR complexed with six different statins. The statins occupy a portion of the binding site of HMG-CoA, thus blocking access of this substrate to the active site. Near the carboxyl terminus of HMGR, several catalytically relevant residues are disordered in the enzyme-statin complexes. If these residues were not flexible, they would sterically hinder statin binding.

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Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study.

Shengxu Li, Wei Chen, Sathanur R. Srinivasan … (2003)

Carotid artery intima-media thickness (IMT) is associated with cardiovascular risk factors and is recognized as an important predictive measure of clinical coronary atherosclerosis events in middle-aged and elderly populations. However, information on the association of carotid IMT in young adults with different risk factors measured in childhood, adulthood, or as a cumulative burden of each of the risk factors measured serially from childhood to adulthood is limited. To examine the association between carotid IMT in young adults and traditional cardiovascular risk factors measured since childhood. A cohort study of 486 adults aged 25 to 37 years from a semirural black and white community in Bogalusa, La (71% white, 39% men), who had at least 3 measurements of traditional risk factors since childhood, conducted between September 1973 and December 1996. Association of carotid IMT with risk factors, including systolic blood pressure, lipoprotein levels, and body mass index. Male vs female (0.757 mm vs 0.719 mm) and black vs white (0.760 mm vs 0.723 mm) participants had increased carotid IMT (P<.001 for both). In multivariable analyses, significant predictors for being in top vs lower 3 quartiles of carotid IMT in young adults were childhood measures of low-density lipoprotein cholesterol (LDL-C) level (odds ratio [OR], 1.42, corresponding to 1-SD change specific for age, race, and sex; 95% confidence interval [CI], 1.14-1.78) and body mass index (BMI; OR, 1.25; 95% CI, 1.01-1.54); adulthood measures of LDL-C level (OR, 1.46; 95% CI, 1.16-1.82), high-density lipoprotein cholesterol (HDL-C) level (OR, 0.67; 95% CI, 0.51-0.88), and systolic blood pressure (OR, 1.36; 95% CI, 1.08-1.72); and long-term cumulative burden of LDL-C (OR, 1.58; 95% CI, 1.24-2.01) and HDL-C (OR, 0.75; 95% CI, 0.58-0.97) levels measured serially from childhood to adulthood. An increasing trend in carotid IMT across quartiles of LDL-C level measured in childhood was observed, with a mean value of 0.761 mm (95% CI, 0.743-0.780 mm) for those at the top quartile vs 0.724 mm (95% CI, 0.715-0.734 mm) for those in the lower 3 quartiles (P<.001). Childhood measures of LDL-C level and BMI predict carotid IMT in young adults. The prevention implications of these findings remains to be explored.

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Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study.

P Gard, J Cresanta, L Webber … (1986)

We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.