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.

Lipoproteína (a) em pacientes portadores de doença arterial obstrutiva periférica e/ou diabetes mellitus tipo 2 / Lipoprotein (a) in patients with peripheral arterial obstructive disease and/or type 2 diabetes mellitus

INTRODUÇÃO: A doença arterial obstrutiva periférica (DAOP) constitui um excelente marcador para a aterosclerose sistêmica. Entre os fatores de risco para essa doença está o diabetes mellitus tipo 2 (DM2). Acredita-se que a lipoproteína (a) [Lp(a)] esteja ligada a risco aumentado de aterosclerose, embora os mecanismos que levem a esse aumento não sejam completamente conhecidos. Níveis elevados de Lp(a) parecem estar associados a risco aumentado de doença arterial coronariana (DAC), assim como DAOP e doença cerebrovascular. OBJETIVO: Avaliar os níveis plasmáticos de Lp(a) e outras variáveis lipídicas em um grupo de pacientes com DAOP e/ou DM2. MATERIAL E MÉTODOS: Níveis plasmáticos de Lp(a), colesterol total (CT), colesterol da lipoproteína de alta densidade (HDL-c), colesterol da lipoproteína de baixa densidade (LDL-c), triglicérides (TG) e apolipoproteínas A-I e B foram medidos em amostras de sangue de 12 indivíduos comprovadamente não-portadores de DAOP e DM2 (controles), 17 pacientes portadores de DAOP, 18 pacientes com DM2 e 19 pacientes portadores de DAOP e DM2 simultaneamente. Os participantes desse estudo foram selecionados buscando-se homogeneidade e semelhança estatística em relação às variáveis sexo, idade e nível socioeconômico. RESULTADOS: A Lp(a) apresentou tendência a elevação tanto no grupo de pacientes com DAOP quanto naquele com DM2 + DAOP. Foram encontradas diferenças significativas entre os grupos para as dosagens de HDL-c e Apo A-I, inclusive com correlação positiva entre esses parâmetros. A relação CT/HDL-c apresentou diferença estatística significativa entre os grupos. Foram observadas correlações positiva entre Lp(a) e LDL-c, e negativa entre o índice tornozelo-braquial (ITB) e a Lp(a). CONCLUSÃO: Para as variáveis lipídicas estudadas foram observadas diferenças estatísticas significativas apenas entre os níveis plasmáticos de HDL-c e Apo A-I. Para o parâmetro Lp(a) foram observados níveis plasmáticos mais elevados...

BACKGROUND: Peripheral arterial obstructive disease (PAOD) constitutes an excellent marker for systemic atherosclerosis and type 2 diabetes mellitus (DM2) is among the greatest risk factors for this disease. It is believed that lipoprotein (a) [Lp(a)] is linked to increased risk of atherosclerosis, although the mechanisms responsible for that are not widely known. Elevated levels of Lp(a) seem to be associated with a higher risk of coronary artery disease (CAD), as well as PAOD and cerebrovascular disease. OBJECTIVES: To assess the plasma levels of Lp(a) and other lipid parameters in patients with PAOD and/or DM2. Material and methods: Plasma levels of Lp(a), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and apolipoproteins A-I and B were measured in blood samples of 12 subjects carrying neither PAOD nor DM2 (control group), 17 patients with PAOD, 18 with DM2 and 19 with both PAOD and DM2. The subjects selected for this study showed homogeneity and no statistical difference for gender, age, and socioeconomic status. RESULTS: The Lp(a) showed a tendency to elevation both in groups PAOD only and PAOD + DM2 simultaneously. Significant differences were observed among the groups as to HDL-c and apolipoprotein A-I levels, with positive correlation between these two parameters. TC/HDL-c ratio showed significant difference among the groups. Positive correlation was found between Lp(a) and LDL-c, and negative one, between the ankle-arm index and LP(a). CONCLUSION: As to the lipid parameters studied, significant statistical differences were found between HDL-c and apolipoprotein A-I plasma levels only. For Lp(a) parameter, higher plasma levels were observed in PAOD and PAOD + DM2, which have also shown concomitant and significant HDL-c reduction.

Elevados niveles séricos de lipoproteína (a) en una población afro-venezolana / High serum (a) in a afro-venezuelan population

Altas concentraciones de Lipoproteína (a) [Lp)a)] son consideradas un factor de riesgo independiente para la enfermedad cardiovascular, sin embargo su determinación no se realiza como prueba de rutina en la evaluación de dicho riesgo. El propósito de este estudio fue determinar los niveles séricos de Lp(a) en individuos de las poblaciones de Maracaibo, una localidad con predominio blanco-hispánico, y de Bobures, una localidad afrovenezolana, ambas ubicadas en el Estado Zulia, Venezuela. para ello se seleccionaron al azar un total de 112 individuos, 57 de Maracaibo (edad promedio 41,8 ± 13,5 años), y 55 de Bobures (edad promedio 31,4 ± 17,4 años) a los cuales se les determinó en condiciones basales glicemia, perfil lípidico y Lp(a). Para la cuantificación sérica de Lp(a) fue utilizado un Kit comercial basado en ELISA de doble anticuerpo monoclonal contra apo-B100 y contra apo(a) (Heber Biotech BioSCREEN Lp(a), La Habana, Cuba). El colesterol total y el colesterol de HDL fueron significativamente más elevados en los individuos de Maracaibo que en los de Bobures (p<0.009 y p<0.001 respectivamente), mientras que los niveles de Lp(a) séricos fueron significativamente más elevados (p<0.001 en la población afrovenezolana (media de 59,0 mg/dl) que en los blancos hispánicos) (media de 29,0 mg/dl). Nuestros rsultados sugieren que la población afrovenezolana estudiada al tener concentraciones de Lp(a) dos veces más elevada que la muestra de blancos-hispánicos estudiados y por encima del rango normal de 30 mg/dl, tienen un mayor riesgo de enfermedad cardiovascular, por lo tanto deben ser realizados estudios destinados a determinar de los subtipos de Lp(a) presentes en esta población

Lipoprotein(a) as a marker of coronary artery disease and its association with dietary fat.

OBJECTIVE: The main objectives of the study were to evaluate the effect of dietary fat on plasma lipoprotein(a) [Lp(a)] levels and to study the potential of Lp(a) as a more reliable marker for CAD compared to other lipids and lipoproteins. METHODS: Twenty CAD patients and 20 healthy controls were recruited for the study. Their fasting plasma Lp(a) levels and complete lipid profile were assayed. The fat intake was calculated using 24 hours dietary recall method. The patients and controls were each divided into two subgroups: Group A consuming dietary fat > 30% and Group B consuming dietary fat < or = 30% of the total kilo-calories/day. RESULTS: Results indicated that plasma Lp(a), total serum cholesterol (TC), tryglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio of CAD patients were significantly higher than the controls. High fat intake was found to be associated with higher plasma Lp(a) levels (p<0.05) in patients only. No significant correlation was found between Lp(a) levels and other conventional lipoproteins. CONCLUSION: The lack of correlation between Lp(a) and other lipoproteins indicates its potential as an independent risk factor for CAD. High fat intake led to higher plasma Lp(a) levels in patients; hence it would be worthwhile to evaluate the effect of quality and quantity of fat intake on plasma Lp(a) levels in a larger sample size.

Estudo de parâmetros bioquímicos e biológicos no hipotireoidismo sub-clínico / Study of biochemical and biological parameters in subclinical hypothyroidism

O objetivo deste trabalho foi o estudo de parametros bioquimicos (homocisteina,Lp(a), ApoA e ApoB) e biologicos (dilatação arterial endotélio dependente e dilatação arterial após nitrato sublingual) em mulheres com hipotireoidismo sub-clinico;nas pacientes que apresentaram alteração nos parametros biologicos foram estudados novamente todos os parametros,bioquimicos e biologicos após o tratamento com levotiroxina.Os resultados mostraram alteração na dilatação arterial endotélio / The objective of this work was to study biochemical ( homocysteine,Lp(a),ApoA and ApoB) and biological ( endothelium-dependent arterial dilation and arterial dilation after sublingual nitrate) parameters in women with subclinical hypothyroidism;in patients with abnormal biological parameters,biochemical and biological parameters were studied again after levothyroxine therapy.Results show abnormal endothelium-dependent arterial dilation...

Serum levels of lipoprotein (a) and other lipids in angiographically defined coronary artery disease patients and healthy blood bank donors.

Lipoprotein (a) (Lp(a)) and other lipid values have been correlated with angiographically defined [table: see text] coronary artery disease. To study this relationship in Indian patients, plasma levels of Lipoprotein (a) and other lipids were assessed in 74 patients undergoing Coronary arteriography and also in 53 age and sex matched healthy male blood bank donors who served as controls. Total cholesterol (mg/dl) (211 +/- 56 vs 186 +/- 43; p < 0.001), low density lipoprotein Cholesterol (mg/dl) (117 +/- 40 vs 88 +/- 29; p > 0.001) and low density lipoprotein/high density lipoprotein cholesterol ratio (2.6 +/- 0.8 vs 2.2 +/- 0.9; p < .001) were significantly higher in patients than controls. High density lipoprotein-cholesterol (mg/dl) (43.5 +/- 6 vs 42.1 +/- 7; p-ns) very low density lipoprotein-cholesterol (mg/dl) (49.7 +/- 17 vs 56.1 +/- 25; p-ns) and triglycerides (mg/dl) (155 +/- 101 vs 167 +/- 88; p-ns) were not statistically different in two groups. Lipoprotein (a) levels showed highly skewed distribution. Patients (n = 74) showed almost five fold higher lipoprotein (a) levels (mg/dl) as compared to controls (n = 53) [105 +/- 565 vs 23 +/- 76]. Patients with very high lipoprotein (a) levels [values of more than 40 mg/dl] (n = 18) had high density lipoprotein cholesterol and total cholesterol significantly lower than rest of the patient group. [high density lipoprotein cholesterol (mg/dl) 41.00 +/- 3.7 vs 44 +/- 6.4; p < 0.01 and total cholesterol (mg/dl) 192 +/- 34 vs 217 +/- 53; p < 0.05].

Lipoprotein(a) in coronary heart disease: a case-control study.

To determine the significance of lipoprotein(a) levels in coronary heart disease patients, a case-control study was performed with 48 newly diagnosed coronary heart disease patients and 23 controls who were evaluated using clinical history and biochemical examination. Lipoprotein(a) was measured by quantitative latex-enhanced immunoturbidimetric method. Geometric means of biochemical parameters were obtained. Comprehensive lipid tetrad index was calculated using a previously validated formula. There was no significant difference in prevalence of diabetes, hypertension and smoking in cases and controls. Dietary intake of calories, fats, fatty acids and antioxidant vitamins was also similar. The levels of fasting glucose, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were not significantly different in cases and controls (p > 0.05). Low-density lipoprotein/high-density lipoprotein ratio (4.33 +/- 1.5 vs 4.29 +/- 1.8) and total cholesterol/high-density lipoprotein ratio (6.59 + 1.7 vs 6.69 +/- 2.2) were similar. The mean lipoprotein(a) levels were significantly greater in cases (11.95 +/- 2.8 mg/dL, range 1-102 mg/dL) as compared to controls (6.68 +/- 3.4 mg/dL, range 1-73 mg/dL) (t = 2.08, p = 0.041). As compared to controls, in coronary heart disease cases, mean lipoprotein(a) levels in patients upto 50 years (10.27 +/- 2.8 vs 7.27 +/- 3.4 mg/dL) as well as those over 50 years (12.99 +/- 2.9 vs 4.91 +/- 3.5 mg/dL) were significantly more (p < 0.05). Coronary heart disease patients had a slightly greater prevalence of high lipoprotein(a) levels, 20 mg/dL or more (31.3 vs 13.0%; chi 2 = 2.83, l-tailed p < 0.05). Comprehensive lipid tetrad index (total cholesterol x triglycerides x lipoprotein(a) divided by high-density lipoprotein cholesterol) was also slightly higher in cases (14688.2 +/- 3.6) than in controls (8358.2 +/- 4.3) (t = 1.68, 1-tailed p < 0.05). This study shows that lipoprotein(a) levels are significantly more in both younger and older coronary heart disease patients as compared to controls.

Lipoprotein(a) as an independent risk factor for coronary artery disease in patients below 40 years of age.

Coronary artery disease has assumed alarming proportions in Indians and often affects people at younger age. Traditional risk factors fail to explain the high incidence of disease. Although lipoprotein(a) has been shown to be a powerful risk factor for atherosclerosis, there is very limited data with regard to its significance in premature coronary artery disease. The present study was therefore undertaken to assess lipoprotein(a) levels and its role as a marker of coronary artery disease in patients below the age of 40 years. Lipid profile and lipoprotein(a) levels were estimated in 50 patients of angiographically proven coronary artery disease and an equal number of age-matched healthy controls. There was no significant difference in the family history of coronary artery disease, body mass index and waist-hip ratio between the two groups. Total plasma cholesterol, triglyceride and LDL-cholesterol levels were significantly higher and HDL-cholesterol significantly lower in patients as compared to controls. In patients of coronary artery disease, mean lipoprotein(a) levels, measured by ELISA method, were 35.0 +/- 32.4 mg/dL and the median was 26.7 mg/dL. These values were significantly higher than the mean of 20.3 +/- 17.0 mg/dL (p < 0.002) and the median of 13.8 mg/dL (p < 0.015) in controls. Multiple regression analysis, to assess the influence of various risk factors, showed that low HDL-cholesterol (odds ratio 4.62, 95% CI 1.84-11.60; p < 0.015) and elevated lipoprotein(a) levels (odds ratio 3.06, 95% CI 1.24-7.55; p < 0.001) were independent risk factors, whereas high total cholesterol and triglyceride levels did not have any independent influence on premature coronary artery disease. Our data thus suggest that lipoprotein (a) levels are elevated and constitute an independent risk factor in patients with premature coronary artery disease below 40 years of age.

Lipoproteína (a) y riesgo de enfermedad coronaria en hombres hipercolesterolémicos / Lipoprotein (a) as a risk factor for coronary heart disease in hypercholesterolemic men

La Lp(a) es una partícula con capacidad aterogénica que ha sido indicada, con resultados contradictorios, como factor de riesgo coronario. En el presente estudio fueron incluídos 121 hombres con hiperlipidemia severa (valores de colesterol > 30 mg/dl), de los cuales 66 tuvieron evidencias de enfermedad coronaria, y un grupo control de 55 hombres. Se realizó un análisis multivariado con regresión logística, incluyendo las siguientes variables: edad, colesterol, HDL-colesterol, triglicéridos, Lp(a). Los resultados del presente estudio sugieren que la Lp(a) es un parámetro de riesgo independiente en hombres con hiperlipidemia severa, por lo cual su determinación permitiría seleccionar entre los sujetos hiperlipidémicos un subgrupo con mayor riesgo de enfermedad coronaria

Determinación de lipoproteína (a) por electroinmunodifusión / Electroimmunodifusion method for Lp (a) in serum

Los aumentos de la lipoproteína (a) sérica , (Lp(a)), están asociados a un incremento del riesgo para la aterosclerosis a través de su papel atero-trombótico. Para su dosaje en sangre, se desarrolló un método por electroinmunodifusión. Se utilizó un soporte de agarosa al 1,5 por ciento con 30 por ciento de agar (p/p), disuelto en un buffer tris-glicina-veronal sódico, con antisuero específico anti apo (a) y calibrador liofilizado comerciales. El CV por ciento intra-ensayos fue 6,9 por ciento y el CV por ciento inter-ensayos fue 8,8 por ciento. La linealidad se mantuvo entre 5 y 120 mg/dl. Se midió la Lp(a) en 134 sujetos "aparentemente sanos" de ambos sexos. La distribución de valores no fue gaussiana y tuvo una mediana de 10 mg/dl. El percentil 75 fue 33 mg/dl el cual se consideró "valor de corte", para la detección de sujetos en riesgo; el percentil 90 fue 72 mg/dl. Los valores hallados por este método correlacionaron bien con otro método por ELISA, obteniéndose r = + 0,896, P < 0,000001. El congelamiento de los sueros por 45 días a -20ºC no modificó significativamente los valores, hallándose r = + 0,963, P < 0,000001. Se concluye que el método propuesto puede ser utilizado para la determinación de Lp(a) sérica