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. 2019 Jul 9;74(1):54-66.
doi: 10.1016/j.jacc.2019.03.524.

Elevated Lipoprotein(a) and Risk of Ischemic Stroke

Anne Langsted  1 , Børge G Nordestgaard  2 , Pia R Kamstrup  3
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Free article

Elevated Lipoprotein(a) and Risk of Ischemic Stroke

Anne Langsted et al. J Am Coll Cardiol. .
Free article

Erratum in

  • Correction.
    [No authors listed] [No authors listed] J Am Coll Cardiol. 2020 May 12;75(18):2385. doi: 10.1016/j.jacc.2020.03.063. J Am Coll Cardiol. 2020. PMID: 32381173 No abstract available.

Abstract

Background: High lipoprotein(a) is associated with increased risk of myocardial infarction and aortic valve stenosis. Previous studies have examined the association of lipoprotein(a) and risk of stroke; however, the results are conflicting.

Objectives: The purpose of this study was to test if high lipoprotein(a) is associated with high risk of ischemic stroke observationally and causally from human genetics.

Methods: The study included 49,699 individuals from the Copenhagen General Population Study and 10,813 individuals from the Copenhagen City Heart Study with measurements of plasma lipoprotein(a), LPA kringle-IV type 2 number of repeats, and LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and validated by medical doctors.

Results: Compared with individuals with lipoprotein(a) levels <10 mg/dl (<18 nmol/l: first to 50th percentile), the multivariable-adjusted hazard ratio for ischemic stroke was 1.60 (95% confidence interval [CI]:1.24 to 2.05) for individuals with lipoprotein(a) levels >93mg/dl (>199 nmol/L: 96th to 100th percentile). In observational analyses for a 50 mg/dl (105 nmol/l) higher lipoprotein(a) level the age- and sex-adjusted hazard ratio for ischemic stroke was 1.20 (95% CI: 1.13 to 1.28), while the corresponding age- and sex-adjusted genetic causal risk ratio for KIV-2 number of repeats was 1.20 (95% CI: 1.02 to 1.43) and for rs10455872 was 1.27 (95% CI: 1.06 to 1.51). The highest absolute 10-year risk of ischemic stroke was 17% in active smoking individuals >70 years of age with hypertension and lipoprotein(a) levels >93 mg/dl (>199 nmol/l: 96th to 100th percentile). In the Copenhagen City Heart Study, risk estimates for high levels of lipoprotein(a) were in the same direction but did not reach statistical significance.

Conclusions: In a large contemporary general population study, high plasma levels of lipoprotein(a) were associated with increased risk of ischemic stroke both observationally and causally from human genetics.

Keywords: epidemiology; genetics; kringle IV type 2; lipoproteins; lp(a).

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