Abstract
BACKGROUND AND PURPOSE: We tested the hypothesis that observationally and genetically elevated YKL-40 is associated with elevated lipids and lipoproteins and with increased risk of ischemic vascular disease.
METHODS: We conducted cohort and Mendelian randomization studies in 96 110 individuals from the Danish general population, with measured plasma levels of YKL-40 (n=21 647), plasma lipids and lipoproteins (n=94 461), and CHI3L1 rs4950928 genotype (n=94 579).
RESULTS: From 1977 to 2013, 3256 individuals developed ischemic stroke, 5629 ischemic cerebrovascular disease, 4183 myocardial infarction, and 10 271 developed ischemic heart disease. The 91% to 100% versus 0% to 33% YKL-40 percentile category was associated with a 34% increase in triglycerides, but only with minor changes in other lipids and lipoproteins. For these categories, the multifactorially adjusted hazard ratio was 1.99 (95% confidence interval, 1.49-2.67) for ischemic stroke, 1.85 (1.44-2.37) for ischemic cerebrovascular disease, 1.28 (0.95-1.73) for myocardial infarction, and 1.23 (1.01-1.51) for ischemic heart disease. When compared with rs4950928 CC homozygosity, the presence of G-allele was associated with a doubling (GC) or tripling (GG) in YKL-40 levels, but not with triglyceride levels or with risk of ischemic vascular disease. A doubling in YKL-40 was associated with a multifactorially adjusted observational hazard ratio for ischemic stroke of 1.18 (1.11-1.27), and a genetic odds ratio of 1.04 (0.95-1.15). Corresponding risk estimates were 1.15 (1.09-1.22) observationally and 1.06 (0.99-1.14) genetically for ischemic cerebrovascular disease, 1.08 (1.00-1.15) observationally and 1.04 (0.96-1.13) genetically for myocardial infarction, and 1.07 (1.02-1.12) observationally and 1.01 (0.96-1.07) genetically for ischemic heart disease.
CONCLUSIONS: Elevated YKL-40 was associated with a 34% increase in triglyceride levels and with a 2-fold increased risk of ischemic stroke, whereas genetically elevated YKL-40 were not.
| Original language | English |
|---|---|
| Journal | Stroke |
| Volume | 46 |
| Issue number | 2 |
| Pages (from-to) | 329-35 |
| Number of pages | 7 |
| ISSN | 0039-2499 |
| DOIs | |
| Publication status | Published - 6 Feb 2015 |
Keywords
- Adipokines
- Aged
- Biomarkers
- Cerebrovascular Disorders
- Cohort Studies
- Female
- Humans
- Lectins
- Lipids
- Lipoproteins
- Male
- Middle Aged
- Myocardial Infarction
- Myocardial Ischemia
- Population Surveillance
- Prospective Studies
- Risk Factors
- Stroke
- Triglycerides
- Vascular Diseases