Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: Recent Advances and Future Directions

Marcovina, Santica M.; Koschinsky, Marlys L.; Albers, John J.; Skarlatos, Sonia I.

doi:10.1373/clinchem.2003.023689

Cited by 243 publications

(207 citation statements)

References 87 publications

Supporting

Mentioning

188

Contrasting

Unclassified

Order By: Relevance

“…At present, Lp(a) is not an established cardiovascular risk factor and there are no guidelines recommending intervention. 42,123 Our current level of understanding would suggest that Lp(a) lowering might be beneficial in white men and some other subgroups of patients with high Lp(a) levels, but we still lack enough details on how to define such subgroups with regard to Lp(a) levels, apo(a) size, and presence of other risk factors. Additionally, the lack of knowledge of Lp(a) metabolism both regarding its formation and catabolism raises considerable challenges in devising strategies to lower Lp(a) levels.…”

Section: Approaches To Modulate Lp(a) Levels: Challenges and Possibilmentioning

confidence: 99%

“…The use of molar units (eg, nmol/L) is therefore preferable and this is facilitated by recent progress in the standardization of Lp(a) measurements. 42 Because there is profound interindividual variation in Lp(a) levels for a given apo(a) size, suggesting that factors beyond gene size predict plasma levels, interest has focused on other apo(a) gene variations. Several polymorphisms in the apo(a) gene have been reported.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lipoprotein(a)

Berglund

Ramakrishnan

2004

ATVB

203

View full text Add to dashboard Cite

Abstract-Lipoprotein (a) [Lp(a)], is present only in humans, Old World nonhuman primates, and the European hedgehog.Lp(a) has many properties in common with low-density lipoprotein (LDL) but contains a unique protein, apo(a), which is structurally different from other apolipoproteins. The size of the apo(a) gene is highly variable, resulting in the protein molecular weight ranging from 300 to 800 kDa; this large variation may be caused by neutral evolution in the absence of any selection advantage. Apo(a) influences to a major extent metabolic and physicochemical properties of Lp(a), and the size polymorphism of the apo(a) gene contributes to the pronounced heterogeneity of Lp(a). There is an inverse relationship between apo(a) size and Lp(a) levels; however, this pattern is complex. For a given apo(a) size, there is a considerable variation in Lp(a) levels across individuals, underscoring the importance to assess allele-specific Lp(a) levels. Further, Lp(a) levels differ between populations, and blacks have generally higher levels than Asians and whites, adjusting for apo(a) sizes. In addition to the apo(a) size polymorphism, an upstream pentanucleotide repeat (TTTTA n ) affects Lp(a) levels. Several meta-analyses have provided support for an association between Lp(a) and coronary artery disease, and the levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with cardiovascular disease or with preclinical vascular changes. Further, there is an interaction between Lp(a) and other risk factors for cardiovascular disease. The physiological role of Lp(a) is unknown, although a majority of studies implicate Lp(a) as a risk factor. Key Words: atherosclerosis Ⅲ genetics Ⅲ blacks Ⅲ lipids L ipoprotein(a) [Lp(a)] was first described Ϸ40 years ago, and interest in this entity is largely derived from its putative role as a cardiovascular risk factor. 1-3 Underlying this concept is the realization that Lp(a) has many properties in common with low-density lipoprotein (LDL), a wellestablished atherogenic factor for coronary artery disease. [2][3][4][5] Thus, the composition of the lipid moiety of Lp(a), including its cholesteryl ester-rich core, is similar to that of LDL, and the density distribution of the lipid moiety of Lp(a) in a given subject closely mirrors that of LDL. 6 Furthermore, like LDL, each particle of Lp(a) has 1 molecule of apolipoprotein B-100 (apo B-100); both apolipoprotein B (apoB) and the lipid core are pro-atherogenic. 7 Also, Lp(a) clearance rates are similar to those for LDL. 8,9 However, Lp(a) contains a unique protein, apolipoprotein(a) [apo(a)], which is structurally different from other apolipoproteins, having a hydrophilic, carbohydrate-rich structure with no amphipathic helices. 5,10,11 Apo(a) is linked to apoB through a single disulfide bond connecting their C-terminal regions [12][13][14][15] (Figure 1).The presence of apo(a) influences to a major extent metabolic and physicochemical properties of Lp(a). 16 -18 Notably, the cysteine residue in apoB involved in ...

show abstract

Section: Approaches To Modulate Lp(a) Levels: Challenges and Possibilmentioning

confidence: 99%

mentioning

confidence: 99%

Lipoprotein(a)

Berglund

Ramakrishnan

2004

ATVB

203

View full text Add to dashboard Cite

show abstract

“…Entretanto esse fato não ocorreu no grupo DM + HASmAlb. Os níveis plasmáticos de Lp(a) e a sua massa molecular são muito variáveis entre as pessoas, sendo determinados geneticamente (17) . Contudo certas anormalidades metabólicas podem influenciar as concentrações circulantes de Lp(a).…”

Section: Discussionunclassified

Correlação entre os níveis plasmáticos de apolipoproteínas A-I e B e o perfil lipídico em indivíduos com e sem diabetes mellitus tipo 2 e hipertensão arterial

Lima¹,

Carvalho²,

Soares³

et al. 2005

J. Bras. Patol. Med. Lab.

View full text Add to dashboard Cite

y unitermos key words resumo Introdução: As dislipidemias, o diabetes mellitus (DM) e a hipertensão arterial sistêmica (HAS) são importantes fatores no desenvolvimento da doença arterial coronariana (DAC), a principal causa de morte de indivíduos adultos no mundo. Diversos estudos têm demonstrado correlação positiva entre concentrações plasmáticas elevadas de colesterol presente na lipoproteína de baixa densidade (LDL-C) e/ou baixas concentrações de colesterol presente na lipoproteína de alta densidade (HDL-C) e aumento de risco para doenças cardiovasculares (DCV). Objetivo: Correlacionar os valores do perfil lipídico, apolipoproteínas (Apo) A-I e B, lipoproteína(a) [Lp(a)] e microalbuminúria em indivíduos com e sem DM e HAS. Material e métodos: Os participantes, com faixa etária de 40 a 65 anos, foram divididos em cinco grupos: 1. controle (indivíduos hígidos, n = 16); 2. HAS (hipertensos, n = 12); 3. DM (DM2, normotensos e normoalbuminúricos, n = 7); 4. DM + HASnAlb (DM2, hipertensos e normoalbuminúricos, n = 18); e 5. DM + HASmAlb (DM2, hipertensos e microalbuminúricos, n = 9). Resultados: Foram observadas diferenças estatísticas para o LDL-C entre a média do grupo 5 em relação às médias dos demais grupos; para triglicérides (TGL), entre as médias dos grupos 2, 4 e 5 em relação à do grupo 1. Para as médias de colesterol total (CT), HDL-C, Lp(a) e Apo A-I não houve diferença significativa entre os grupos. As médias para Apo B dos grupos 4 e 5 apresentaram diferenças significativas com relação ao grupo 1. Foi observada correlação positiva entre o LDL-C e a Apo B (r = 0,684); p < 0,0001) e entre o HDL-C e a Apo A-I (r = 0,374; p = 0,003), de acordo com a literatura. Conclusão: Entre todos os parâmetros avaliados o LDL-C foi o único que apresentou diferenças significativas entre o grupo 5, cujos indivíduos apresentam as duas patologias combinadas (DM e HAS), além da microalbuminúria, em relação aos demais grupos estudados, sugerindo que a associação das duas patologias, aliada à presença de microalbuminúria, poderia ter contribuído para o agravamento da dislipidemia. Perfil lipídico ApolipoproteínasDiabetes mellitus tipo 2 A-I and B, Lipoprotein(a) 684); p < 0,0001) and 374; p = 0,003), according to literature. Conclusion: Among all parameters assessment, LDL-C was the unique one that showed significant differences between the group 5, whose participants present both alterations (DM and HAS) besides the microalbuminuria, related to other groups studied. This comes to suggest that the association between the two diseases allied to microalbuminuria may contribute to the dyslipidemia aggravation. Hipertensão arterial abstract Background: Dyslipidemias, diabetes mellitus (DM), high blood pressure are important factors for development of the coronary artery disease (CAD), principal cause of death in the world. Several studies have demonstrated positive correlation between both LDL-C high plasma levels and HDL-C low concentrations and increased risk for cardiovascular diseases. Objectives: To establish the possi...

show abstract

“…ATP-III kılavuzu temel alındığında, Lp(a) KVH için gittikçe önem kazanan lipid risk faktörlerinden biridir 29 . NHLBI'nın bir raporunda, NCEP kılavuzlarına göre, Amerika'da KKH gelişimi açısından yüksek riskli bireylerin %37'sinde serum Lp(a) düzeyleri yüksek iken, düşük riskli bireylerin ancak %14'ünde Lp(a) düzeyleri yüksek hesaplanmış-tır 32 . "Atherosclerosis Risk in Communities (ARIC)" çalışmasında diğer lipidlerden bağımsız istatistiksel anlamlılığı ortaya konmuş olsa da ölçüm maliyeti, diğer lipid risk faktörlerine Lp(a)'nın eklenmesinin KKH öngörüsüne getireceği ekstra kazancın henüz ciddi boyutlarda olmaması, doğrudan terapötik girişimin henüz var olmaması, yükselmiş Lp(a) düzeyinin teda-visinin ileride oluşacak kardiyovasküler olayları kesin azalttığına dair geçerli veri olmaması nedeniyle, Lp(a) ölçümünün klinikte kullanımının günümüz şartların-da iyice sorgulanması gerektiği bir gerçektir 33 .…”

Section: Gereç Ve Yöntemunclassified