Lipoprotein (a) level, apolipoprotein (a) size, and risk of unexplained ischemic stroke in young and middle-aged adults

Azadeh Beheshtian, Sanyog G. Shitole, Alan Z. Segal, Dana Leifer, Russell P. Tracy, Daniel J. Rader, Richard B. Devereux, Jorge Kizer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background and aims Circulating lipoprotein (a) [Lp(a)] level relates inversely to apolipoprotein (a) [apo(a)] size. Both smaller apo(a) isoforms and higher Lp(a) levels have been linked to coronary heart disease and stroke, but their independent contributions are less well defined. We examined the role of Lp(a) in younger adults with cryptogenic stroke. Methods Lp(a) and apo(a) isoforms were evaluated in a prospectively designed case-control study of patients with unexplained ischemic stroke and stroke-free controls, ages 18 to 64. Serum Lp(a) was measured among 255 cases and 390 controls with both apo(a)-size independent and dependent assays. Apo(a) size was determined by agarose gel electrophoresis. Results Cases and controls were similar in socio-demographic characteristics, but cases had more 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 versus lowest quartile in whites was significant for apo(a)-size-independent (OR = 2.10 [95% CI = 1.04, 4.27], p = 0.040), and near-significant for apo(a)-size-dependent Lp(a) (OR = 1.81 [95% CI = 0.95, 3.47], p = 0.073). Apo(a) size was not associated with cryptogenic stroke in any race-ethnic subgroup. Conclusions This study underscores the importance of Lp(a) level, but not apo(a) size, as an independent risk factor for unexplained ischemic stroke in young and middle-aged white adults. Given the emergence of effective Lp(a)-lowering therapies, these findings support routine testing for Lp(a) in this setting, along with further research to assess the extent to which such therapies improve outcomes in this population.

Original languageEnglish (US)
Pages (from-to)47-53
Number of pages7
JournalAtherosclerosis
Volume253
DOIs
StatePublished - Oct 1 2016

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Apoprotein(a)
Lipoprotein(a)
Stroke
Protein Isoforms
Social Adjustment
Migraine with Aura
Agar Gel Electrophoresis
Hispanic Americans
Coronary Disease
Case-Control Studies
Young Adult
Smoking
Demography
Hypertension

Keywords

  • Case control study
  • Lipoprotein (a)
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lipoprotein (a) level, apolipoprotein (a) size, and risk of unexplained ischemic stroke in young and middle-aged adults. / Beheshtian, Azadeh; Shitole, Sanyog G.; Segal, Alan Z.; Leifer, Dana; Tracy, Russell P.; Rader, Daniel J.; Devereux, Richard B.; Kizer, Jorge.

In: Atherosclerosis, Vol. 253, 01.10.2016, p. 47-53.

Research output: Contribution to journalArticle

Beheshtian, Azadeh ; Shitole, Sanyog G. ; Segal, Alan Z. ; Leifer, Dana ; Tracy, Russell P. ; Rader, Daniel J. ; Devereux, Richard B. ; Kizer, Jorge. / Lipoprotein (a) level, apolipoprotein (a) size, and risk of unexplained ischemic stroke in young and middle-aged adults. In: Atherosclerosis. 2016 ; Vol. 253. pp. 47-53.
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AU - Shitole, Sanyog G.

AU - Segal, Alan Z.

AU - Leifer, Dana

AU - Tracy, Russell P.

AU - Rader, Daniel J.

AU - Devereux, Richard B.

AU - Kizer, Jorge

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N2 - Background and aims Circulating lipoprotein (a) [Lp(a)] level relates inversely to apolipoprotein (a) [apo(a)] size. Both smaller apo(a) isoforms and higher Lp(a) levels have been linked to coronary heart disease and stroke, but their independent contributions are less well defined. We examined the role of Lp(a) in younger adults with cryptogenic stroke. Methods Lp(a) and apo(a) isoforms were evaluated in a prospectively designed case-control study of patients with unexplained ischemic stroke and stroke-free controls, ages 18 to 64. Serum Lp(a) was measured among 255 cases and 390 controls with both apo(a)-size independent and dependent assays. Apo(a) size was determined by agarose gel electrophoresis. Results Cases and controls were similar in socio-demographic characteristics, but cases had more 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 versus lowest quartile in whites was significant for apo(a)-size-independent (OR = 2.10 [95% CI = 1.04, 4.27], p = 0.040), and near-significant for apo(a)-size-dependent Lp(a) (OR = 1.81 [95% CI = 0.95, 3.47], p = 0.073). Apo(a) size was not associated with cryptogenic stroke in any race-ethnic subgroup. Conclusions This study underscores the importance of Lp(a) level, but not apo(a) size, as an independent risk factor for unexplained ischemic stroke in young and middle-aged white adults. Given the emergence of effective Lp(a)-lowering therapies, these findings support routine testing for Lp(a) in this setting, along with further research to assess the extent to which such therapies improve outcomes in this population.

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