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CLINICAL RESEARCH: METABOLIC SYNDROME, DYSLIPIDEMIA, AND VASCULAR ABNORMALITIES

High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort

^* Department of Medicine, Columbia University, New York, New York, USA

Manuscript received March 3, 2003; revised manuscript received August 8, 2003, accepted August 18, 2003.

^* Reprint requests and correspondence: Dr. Henry D. Wu, Division of Cardiology, Columbia University, 630 West 168th Street (PH342), New York, New York 10032, USA.
hdw1{at}columbia.edu

OBJECTIVES: This study sought to determine the effect of lipoprotein(a), or Lp(a), levels and apolipoprotein(a), or apo(a), sizes on endothelial function and to explore ethnic differences in their effects.

BACKGROUND: Although high levels of Lp(a) have been shown to confer increased cardiovascular risk in Caucasians, its significance in non-Caucasian populations is uncertain. The pathogenic role of the apo(a) component of Lp(a) is also unclear.

METHODS: The relationship of Lp(a) levels and apo(a) sizes to endothelial function was examined in a multiethnic cohort of 89 healthy subjects (age 42 ± 9 years; 50 men, 39 women) free of other cardiac risk factors. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent, nitrate-induced dilation (NTG) were assessed by ultrasound imaging of the brachial artery.

RESULTS: Plasma Lp(a) levels were lowest in Caucasians (18.3 ± 21.1 mg/dl, n = 40); intermediate in Hispanics (30.2 ± 30.5 mg/dl, n = 21); and highest in African Americans (68.8 ± 46.0 mg/dl, n = 28). Lipoprotein(a) levels were found to correlate inversely to FMD (r = –0.33, p < 0.005) but not to NTG (r = 0.06, p = 0.60). This association remained significant after adjusting for gender (p = 0.002). In addition, subjects with small apo(a) size of 22 kringle 4 repeats had significantly lower FMD than those with large apo(a) (2.23 ± 2.37% vs. 6.26 ± 4.29%, p < 0.0001), irrespective of Lp(a) levels.

CONCLUSIONS: These findings support an independent role of Lp(a) in atherogenesis, an effect that is particularly evident in African Americans. The proatherogenic property of Lp(a) can be attributed in part to its apo(a) component.

Abbreviations and Acronyms   apo(a) = apolipoprotein(a)   FMD = flow-mediated dilation   HDL = high-density lipoprotein   K4 = kringle 4   LDL = low-density lipoprotein   Lp(a) = lipoprotein(a)   NTG = nitrate-induced dilation

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