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Study Title:

Nonfasting Triglycerides and Risk of Stroke

Study Abstract

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.

From press release:

Elevated nonfasting triglyceride levels, previously associated with an increased risk for heart attack, also appear to be associated with an increased risk for ischemic stroke, according to a new study.

Recent studies found a strong association between elevated levels of nonfasting triglycerides, which indicate the presence of remnant (a small portion that remains) lipoproteins, and increased risk of ischemic heart disease. "It is therefore possible that nonfasting triglyceride levels are also associated with increased risk of ischemic stroke," the authors write. "Triglyceride levels are usually measured after an 8- to 12-hour fast, thus excluding most remnant lipoproteins; however, except for a few hours before breakfast, most individuals are in the nonfasting state most of the time. Therefore, by mainly studying fasting rather than nonfasting triglyceride levels, several previous studies may have missed an association between triglycerides and ischemic stroke."

Jacob J. Freiberg, M.D., of Copenhagen University Hospitals, Denmark, and colleagues conducted a study to determine if increased levels of nonfasting triglycerides are associated with risk of ischemic stroke. The Copenhagen City Heart Study, a Danish population–based study initiated in 1976 with follow-up through July 2007, included 13,956 men and women age 20 through 93 years. Participants had their nonfasting triglyceride levels measured at the beginning of the study and at follow-up examinations.

Of the 13,956 participants in the study, 1,529 developed ischemic stroke. The researchers found that the cumulative incidence of ischemic stroke increased with increasing levels of nonfasting triglycerides. Men with elevated nonfasting triglyceride levels of 89 through 176 mg/dL had a 30 percent higher risk for ischemic stroke; for levels 177 through 265 mg/dL, there was a 60 percent increased risk; for 266 through 353 mg/dL, a 50 percent higher risk; for 354 through 442 mg/dL, a 2.2 times elevated risk; and for 443 mg/dL or greater, the risk of ischemic stroke was 2.5 times greater compared to men with nonfasting levels less than 89 mg/dL.

Corresponding values for women were a 30 percent increased risk of ischemic stroke for nonfasting triglyceride levels of 89 through 176 mg/dL; twice the risk for levels 177 through 265 mg/dL; a 40 percent higher risk for levels of 266 through 353 mg/dL; 2.5 times the risk for 354 through 442 mg/dL; and 3.8 times the risk for ischemic stroke for women with nonfasting triglyceride levels of 443 mg/dL or greater compared to women with nonfasting triglyceride levels less than 89 mg/dL.

Absolute 10-year risk of ischemic stroke ranged from 2.6 percent in men younger than 55 years with nonfasting triglyceride levels of less than 89 mg/dL to 16.7 percent in men age 55 years or older with levels of 443 mg/dL or greater. These values in women were 1.9 percent and 12.2 percent, respectively. Men with a previous ischemic stroke vs. controls had nonfasting triglyceride levels of 191 mg/dL vs. 148 mg/dL; for women, these values were 167 mg/dL vs. 127 mg/dL.

"By using levels of nonfasting rather than fasting triglycerides and by having more statistical power than any previous study, we detected a previously unnoticed association between linear increases in levels of nonfasting triglycerides and stepwise increases in risk of ischemic stroke …", the authors write. "Even the most recent European and North American guidelines on stroke prevention do not recognize elevated triglyceride levels as a risk factor for stroke."

"Our results, together with those from 2 previous studies, suggest that elevated levels of nonfasting triglycerides and remnant lipoprotein cholesterol could be considered together with elevated levels of low-density lipoprotein cholesterol for prediction of cardiovascular risk. However, these findings require replication in other populations."

Study Information

Jacob J. Freiberg; Anne Tybjaerg-Hansen; Jan Skov Jensen; Borge G. Nordestgaard.
Nonfasting Triglycerides and Risk of Ischemic Stroke in the General Population.
JAMA
2008 November
Copenhagen University Hospitals, Denmark