Abstract 17067: Circulating Lipoprotein (a) Level, Apolipoprotein (a) Isoform Size, and Risk of Unexplained Ischemic Stroke in Younger Adults (The THrombophilia in Cryptogenic stroKe [THICK] Study)
Background: Lipoprotein (a) [Lp(a)] comprises an apolipoprotein (a) [apo(a)] molecule that contains a variable number of kringle IV type 2 (KIV-2) repeats. KIV-2 number determines Lp(a) size but relates inversely to serum Lp(a) levels. Both smaller apo(a) isoforms and higher Lp(a) levels have been linked to coronary heart disease and, less so, stroke, but their independent contributions are less well defined. The role of Lp(a) in younger adults with cryptogenic stroke remains largely unexamined.
Methods: We evaluated Lp(a) and apo(a) isoforms in a prospective case-control study of prothrombotic risk factors for unexplained ischemic stroke in subjects ages 18 to 64. Cases consisted of patients admitted to Weill Cornell Medical Center (2002 [[Unable to Display Character: –]] 2011) with cryptogenic stroke based on modified TOAST criteria. Controls included volunteers recruited from the area. Lp(a) was measured in 255 cases (≥2 months post stroke) or 390 controls with both a molecular-weight (KIV-2 number) independent and a molecular-weight dependent immunoturbidimetric assay. Apo(a) isoform size was determined by agarose gel electrophoresis.
Results: Cases and controls were similar for most characteristics (median age 46 vs 44; women, 39 vs 46%; white 60 vs 63%, black 13 vs 12%, Hispanic 17 vs 18%), but cases had more frequent hypertension, diabetes, smoking, and migraine with aura. In race-specific analyses, Lp(a) levels showed positive associations with cryptogenic stroke in whites, but not in the smaller subgroups of blacks and Hispanics. After full adjustment, comparison of the highest to the lowest quartile in whites was significant for molecular-weight-independent (OR=2.10 [95% CI=1.03, 4.27]), and near-significant for molecular-weight-dependent Lp(a) (OR=1.86 [95% CI=0.97, 3.55]). These associations were unchanged with significant adjustment for apo(a) size. By contrast, apo(a) size was not significantly associated with cryptogenic stroke in any ethnic subgroup.
Conclusions: This study shows that Lp(a) level, but not apo(a) isoform size, is an independent risk factor for unexplained ischemic stroke in young and middle-aged adults of European descent. Future studies will need to examine this association in sufficiently powered samples for other ethnic groups.
Author Disclosures: A. Beheshtian: None. S. Shitole: None. A.Z. Segal: None. R.P. Tracy: None. D. Rader: None. R.B. Devereux: None. J.R. Kizer: Ownership Interest; Significant; Expert Witness work for Pfizer regarding the relationship of PremPro with stroke..
- © 2014 by American Heart Association, Inc.