Affiliation:
1. Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA
2. Divisions of Preventive Medicine and Cardiovascular Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA
3. Warren Alpert School of Medicine, Brown University, Providence, R.I.
Abstract
Background
YKL
‐40, encoded by the chitinase 3‐like 1 (
CHI
3L1
) gene, is a chitinase‐like protein involved in innate immune function hypothesized to play a role in the progression of atherosclerosis that may have differential roles in myocardial infarction (
MI
), as compared to stroke.
Methods and Results
In a nested case‐control study conducted within a prospective cohort of 23 294 initially healthy women of European ancestry, we (1) measured plasma concentration of
YKL
‐40 among 359 participants who subsequently developed cardiovascular events and among 359 age‐, smoking‐, and hormone replacement therapy–matched participants who remained free of disease during 17 years of follow‐up, (2) compared effects of
YKL
‐40 on vascular risk to that associated with 3 alternative inflammatory biomarkers (high‐sensitivity C‐reactive protein) ([hs
CRP
], soluble intracellular adhesion molecule 1, and fibrinogen), and (3) evaluated the role of 41 single‐nucleotide polymorphisms (
SNP
s) in the chitinase 3‐like 1 gene (
CHI
3L1
) as determinants of
YKL
‐40 levels and incident vascular events.
YKL
‐40 levels were higher in women with hypertension, diabetes, and obesity and correlated modestly with high‐density lipoprotein cholesterol, triglycerides, and hs
CRP
, but not with low‐density lipoprotein cholesterol. Baseline
YKL
‐40 level was significantly associated with incident thromboembolic stroke with a magnitude of effect (a 40% per quartile increase in odds ratio [
OR
],
P
=0.019) comparable to that of hs
CRP
(a 52% per quartile increase in
OR
,
P
=0.006). By contrast, no significant association was observed between
YKL
‐40 and incident
MI
. Genetic variation in
CHI
3L1
was strongly associated with
YKL
‐40 levels; however, in this sample set, we did not observe a statistically significant association between genotype and future vascular events.
Conclusions
Among initially healthy U.S. women, plasma levels of the proinflammatory chitenase‐like protein,
YKL
‐40, were influenced by environmental as well as genetic factors and predicted incident thromboembolic stroke, but not
MI
, a differential effect consistent with limited previous data.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine