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Jacob J. Freiberg, MD; Anne Tybjærg-Hansen, MD, DMSc; Jan Skov Jensen, MD, DMSc; Børge G. Nordestgaard, MD, DMSc

JAMA. 2008;300(18):2142-2152.

Context  The role of triglycerides in the risk of ischemic stroke remains controversial. Recently, a strong association was found between elevated levels of nonfasting triglycerides, which indicate the presence of remnant lipoproteins, and increased risk of ischemic heart disease.

Objective  To test the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population.

Design, Setting, and Participants  The Copenhagen City Heart Study, a prospective, Danish population–based cohort study initiated in 1976, with follow-up through July 2007. Participants were 13 956 men and women aged 20 through 93 years. A cross-sectional study included 9637 individuals attending the 1991-1994 examination of the prospective study.

Main Outcome Measures  Prospective study: baseline levels of nonfasting triglycerides, other risk factors at baseline and at follow-up examinations, and incidence of ischemic stroke. Cross-sectional study: levels of nonfasting triglycerides, levels of remnant cholesterol, and prevalence of ischemic stroke.

Results  Of the 13 956 participants in the prospective study, 1529 developed ischemic stroke. Cumulative incidence of ischemic stroke increased with increasing levels of nonfasting triglycerides (log-rank trend, P < .001). Men with elevated nonfasting triglyceride levels of 89 through 176 mg/dL had multivariate-adjusted hazard ratios (HRs) for ischemic stroke of 1.3 (95% CI, 0.8-1.9; 351 events); for 177 through 265 mg/dL, 1.6 (95% CI, 1.0-2.5; 189 events); for 266 through 353 mg/dL, 1.5 (95% CI, 0.9-2.7; 73 events); for 354 through 442 mg/dL, 2.2 (95% CI, 1.1-4.2; 40 events); and for 443 mg/dL or greater, 2.5 (95% CI, 1.3-4.8; 41 events) vs men with nonfasting levels less than 89 mg/dL (HR, 1.0; 85 events) (P < .001 for trend). Corresponding values for women were 1.3 (95% CI, 0.9-1.7; 407 events), 2.0 (95% CI, 1.3-2.9; 135 events), 1.4 (95% CI, 0.7-2.9; 26 events), 2.5 (95% CI, 1.0-6.4; 13 events), and 3.8 (95% CI, 1.3-11; 10 events) vs women with nonfasting triglyceride levels less than 89 mg/dL (HR, 1.0; 159 events) (P < .001 for trend). Absolute 10-year risk of ischemic stroke ranged from 2.6% in men younger than 55 years with nonfasting triglyceride levels of less than 89 mg/dL to 16.7% in men aged 55 years or older with levels of 443 mg/dL or greater. Corresponding values in women were 1.9% and 12.2%. In the cross-sectional study, men with a previous ischemic stroke vs controls had nonfasting triglyceride levels of 191 (IQR, 131-259) mg/dL vs 148 (IQR, 104-214) mg/dL (P < .01); corresponding values for women were 167 (IQR, 121-229) mg/dL vs 127 (IQR, 91-181) mg/dL (P < .05). For remnant cholesterol, corresponding values were 38 (IQR, 26-51) mg/dL vs 29 (IQR, 20-42) mg/dL in men (P < .01) and 33 (IQR, 24-45) mg/dL vs 25 (IQR, 18-35) mg/dL in women (P < .05).

Conclusion  In this study population, nonfasting triglyceride levels were associated with risk of ischemic stroke.

Author Affiliations: Department of Clinical Biochemistry, Herlev Hospital (Drs Freiberg and Nordestgaard), Copenhagen City Heart Study, Bispebjerg Hospital (Drs Tybjærg-Hansen, Jensen, and Nordestgaard), Department of Clinical Biochemistry, Rigshospitalet (Dr Tybjærg-Hansen), and Department of Cardiology, Gentofte Hospital (Dr Jensen), Copenhagen University Hospitals; and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

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