Lipoprotein (a): Structure, Pathophysiology and Clinical Implications / Lipoproteína (a): Estrutura, Metabolismo, Fisiopatologia e Implicações Clínicas

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.

Lp(a) and LDL2: differences in fatty acid composition and collagen lattice contraction activity

Lp (a) and LDL2 were used for detailed fatty acid analyses and tested in an in vitro model promotion of fibroblast-mediated collagen lattice contraction to determine possible compositional and functional differences between these two apoB-containing lipoprotein species. Autologous Lp (a) was more saturated with respect to fatty acid composition than LDL2 in triglyceride and cholesterol ester lipid classes and had differences in the fatty acid content of phospholipids. Functionally, LDL2 promoted rapid fibroblast-mediated contraction while Lp (a) was significantly less active in promoting rapid contraction on a protein per weight basis. These studies suggest a synthetic route for Lp(a) diverging from the majority of other apoB-containing lipoproteins and significant activity of LDL2 in a collagen lattice contraction system.

Lipoproteína (a) y enfermedad coronaria aterosclerótica / Lipoprotein (a) and coronary heart disease

En los últimos años se ha hecho evidente que la lipoproteína (a) se asocia con el desarrollo de enfermedad cardiovascular aterosclerótica. Su concentración plasmática elevada es un predictor independiente de riesgo de infarto de miocardio y de enfermedad coronaria aterosclerótica temprana. Trabajos efectuados in vitro, en vivo y en modelos animales han demostrado el papel fundamental de la lipoproteína (a) en la génesis del proceso aterosclerótico coronario. Estudios clínicos recientes señalan, además, su relación con la reestenosis posangioplastia transluminal coronaria, así como también con la extensión y severidad de las lesiones coronarias. Los recursos terapéuticos para modificar este factor heredado de riesgo son escasos en el momento actual. De su disponibilidad futura podremos obtener una información más completa respecto del papel de la lipoproteína (a) en la fisiología de la enfermedad coronaria aterosclerótica

¿Es la lipoproteína (a) un factor de riesgo de cardiopatía coronaria? / Is lipoprotein (a) a risk factor of coronary cardiopathy?

The serum level of Lp(a) has been defined in retrospective and cross sectional studies as an independent risk factor for acute myocerdial infarction and cerebrovascular thrombotic accidents. However, recent prospective studies have found no evidences of association between Lp(a) levels and risk of myocardial infarction, therefore, current knowledge does not support the measurement of Lp(a) as a screening tool among middle age men. Further research is needed, to identify specific groups where Lp(a) may be a risk factor