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Elevated plasma YKL-40 levels and ischemic stroke in the general population

Authors

  • Alisa D. Kjaergaard MD,

    1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark
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  • Stig E. Bojesen MD, PhD, DMSc,

    1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark
    2. Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
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  • Julia S. Johansen MD, DMSc,

    1. Department of Medicine and Oncology, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
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  • Børge G. Nordestgaard MD, DMSc

    Corresponding author
    1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark
    2. Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
    • Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark
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Abstract

Objective:

We hypothesized that elevated plasma YKL-40 levels are associated with increased risk of ischemic cardiovascular disease in the general population. In contrast to C-reactive protein (CRP) produced in the liver in response to inflammation, YKL-40 is produced by lipid-laden macrophages inside the vessel wall.

Methods:

We measured plasma YKL-40 in 8,899 21- to 93-year-old participants of the Copenhagen City Heart Study 1991–1994 examination, and followed them for up to 18 years. Endpoints were ischemic stroke, ischemic cerebrovascular disease, myocardial infarction, and ischemic heart disease. Hazard ratios were calculated for plasma YKL-40 levels in 10-year age percentile categories of 34 to 66%, 67 to 90%, and 91 to 100% versus 0 to 33%.

Results:

Multifactorially and CRP-adjusted hazard ratios for ischemic stroke were 1.2 (95% confidence interval, 0.9–1.6) for 33 to 66%, 1.8 (1.3–2.4) for 67 to 90%, and 2.3 (1.5–3.3) for 91 to 100% versus the 0 to 33% percentile category (p-trend < 0.001). Corresponding hazard ratios for ischemic cerebrovascular disease were 1.2 (0.9–1.5), 1.6 (1.2–2.0), and 2.2 (1.6–3.2) (p-trend < 0.001). Hazard ratios for myocardial infarction were not significant, whereas corresponding hazard ratios for ischemic heart disease were 1.0 (0.8–1.2), 1.2 (1.0–1.5), and 1.3 (1.0–1.6) (p-trend = 0.01). Stratifying for CRP or other risk factors gave similar results. A doubling in plasma YKL-40 was associated with multifactorially and CRP-adjusted increased risk of 20% (95% confidence interval, 11%–30%) for ischemic stroke, 16% (8%–24%) for ischemic cerebrovascular disease, 3% (-5%–11%) for myocardial infarction, and 7% (1%–12%) for ischemic heart disease.

Interpretation:

In the general population, elevated plasma YKL-40 levels are associated with increased risk of ischemic stroke and ischemic cerebrovascular disease, independent of plasma CRP levels.Ann Neurol 2010;68:672–680

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