Evidence that apolipoprotein(a) phenoptype is a risk factor for coronary artery disease in men &lt; 55 years of age

Parlavecchia, Mariella; Pancaldi, Alessandra; Taramelli, Roberto; Valsania, Paola; Galli, Laura; Pozza, G.; Chierchia, Sergio; Ruotolo, Giacomo

doi:10.1016/0002-9149(94)90401-4

Cited by 31 publications

(18 citation statements)

References 18 publications

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“…The possibility that size variation of apo(a) could be associated with cardiovascular disease has been raised in previous studies, although the results have been inconsistent. 7,[17][18][19][20][21][22][23][24][31][32][33] In several of these studies, only a limited number of apo(a) size isoforms were resolved. 22,23,32 Subsequently, a high-resolution technique allowing separation of Ͼ34 differently sized apo(a) isoforms was introduced.…”

Section: December 2000mentioning

confidence: 99%

“…27 Apo(a) isoforms were classified as being either of small size (Ͻ22 K4 repeats) or large size (Ն22 K4 repeats). [17][18][19][20][21][22][23][24] To validate the apo(a) isoform size determination, we performed genotyping of apo(a) allele sizes by pulsed field electrophoresis. 28 Overall, there was an excellent agreement between the phenotyping and genotyping procedures (rϭ0.997).…”

Section: Apo(a) Isoform Size Determinationmentioning

confidence: 99%

“…26 Elevated Lp(a) levels were defined as Ն30 mg/dL (Ն72 nmol/L). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][17][18][19][20][21][22][23][24] …”

mentioning

confidence: 99%

“…[17][18][19][20][21][22][23][24] In the majority of studies using high-resolution sizing techniques, small apo(a) size has been defined as Ͻ22 kringle 4 (K4) repeats. 17,18,24 The majority of whites with high Lp(a) levels possesses at least 1 small apo(a) isoform; however, the majority of African Americans with high Lp(a) levels has no small apo(a) isoform.…”

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confidence: 99%

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High Levels of Lp(a) With a Small Apo(a) Isoform Are Associated With Coronary Artery Disease in African American and White Men

Paultre

Pearson

Weil

et al. 2000

ATVB

160

132

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Abstract-Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (Ն50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; Pϭ0.004), and only in this group was the presence of small apo(a) isoforms (Ͻ22 kringle 4 repeats) associated with CAD (Pϭ0.043). Elevated Lp(a) levels (Ն30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (PϽ0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a) for cardiovascular disease. [1][2][3] In numerous, but not all, prospective studies, mainly in white populations, elevations of plasma Lp(a) levels, usually defined as Ն30 mg/dL, were significantly correlated with coronary artery disease (CAD). 4 -13 Curiously, although mean Lp(a) levels are twice as high in African Americans compared with whites, studies to date have failed to establish a significant association between elevated Lp(a) levels (Ն30 mg/dL) and CAD among African Americans. 1,14 -16 The lack of understanding of this racial difference has made it difficult to conclude with full confidence that Lp(a) is a risk factor for CAD..In addition to high Lp(a) levels, the presence of small apo(a) isoforms has been associated with CAD in whites. [17][18][19][20][21][22][23][24] In the majority of studies using high-resolution sizing techniques, small apo(a) size has been defined as Ͻ22 kringle 4 (K4) repeats. 17,18,24 The majority of whites with high Lp(a) levels possesses at least 1 small apo(a) isoform; however, the majority of African Americans with high Lp(a) levels has no small apo(a) isoform. 25 The high degree of correlation between elevated levels of Lp(a) and small apo(a) isoforms in whites makes it difficult to ascerta...

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Section: December 2000mentioning

confidence: 99%

Section: Apo(a) Isoform Size Determinationmentioning

confidence: 99%

“…26 Elevated Lp(a) levels were defined as Ն30 mg/dL (Ն72 nmol/L). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][17][18][19][20][21][22][23][24] …”

mentioning

confidence: 99%

mentioning

confidence: 99%

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High Levels of Lp(a) With a Small Apo(a) Isoform Are Associated With Coronary Artery Disease in African American and White Men

Paultre

Pearson

Weil

et al. 2000

ATVB

160

132

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“…In several studies, small apo[a] sizes have been associated with cardiovascular disease (12,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and associations between small apo[a] and cardiovascular disease have remained significant after adjustment for apo [a] level (12, 24-28 Besides the size variation, a C/T polymorphism in the promoter region of the gene (193) and an upstream pentanucleotide repeat (PNR) polymorphism, with 5-12 TTTTA repeats starting at 21,373, have been described in addition to other single-nucleotide polymorphisms (31-38). In transfection experiments, the T nucleotide was associated with lower apo[a] formation as a result of the introduction of a novel start codon (31).…”

mentioning

confidence: 99%

Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]

Rubin

Kim

Pearson

et al. 2006

Journal of Lipid Research

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(16,18,19). In several studies, small apo[a] sizes have been associated with cardiovascular disease (12,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and associations between small apo[a] and cardiovascular disease have remained significant after adjustment for apo [a] level (12, 24-28 Besides the size variation, a C/T polymorphism in the promoter region of the gene (193) and an upstream pentanucleotide repeat (PNR) polymorphism, with 5-12 TTTTA repeats starting at 21,373, have been described in addition to other single-nucleotide polymorphisms (31-38). In transfection experiments, the T nucleotide was associated with lower apo[a] formation as a result of the introduction of a novel start codon (31). In vitro studies of the PNR polymorphism have demonstrated less transcriptional activity for constructs containing nine compared with eight TTTTA repeats (39). In studies in

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Field Inversion Gel Electrophoresis for Apolipoprotein(a) Genotyping

Tavridou

Laker

1999

Analytical Biochemistry

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Evidence that apolipoprotein(a) phenoptype is a risk factor for coronary artery disease in men < 55 years of age

Cited by 31 publications

References 18 publications

High Levels of Lp(a) With a Small Apo(a) Isoform Are Associated With Coronary Artery Disease in African American and White Men

High Levels of Lp(a) With a Small Apo(a) Isoform Are Associated With Coronary Artery Disease in African American and White Men

Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]

Field Inversion Gel Electrophoresis for Apolipoprotein(a) Genotyping

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