Higher Nonfasting Triglycerides Linked With Increased Stroke Risk

A new observational study finds an association between higher levels of nonfasting triglycerides and increasing risk for ischemic stroke.

Using a nonfasting measure of triglycerides in a large population, the researchers report a “previously unnoticed” association between linear increases in triglycerides and a stepwise increase in the risk for ischemic 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,” the researchers, with first author Jacob J. Freiberg, MD, Herlev Hospital, Copenhagen, Denmark, conclude.

Last year, this group reported a relationship between the incidence of myocardial infarction, ischemic heart disease, and death and increasing nonfasting triglyceride levels in both women and men (Nordestgaard BG, et al. JAMA 2007;298:299-308), raising the possibility that they might also be associated with stroke risk. However, the role of triglycerides in the risk for ischemic stroke is controversial, the authors write.

Elevated levels of nonfasting triglycerides indicate the presence of increased levels of remnants from chylomicrons and very low-density lipoprotein cholesterol, they note. “These cholesterol-containing, triglyceride-rich lipoproteins penetrate the arterial endothelium and may get trapped within the subendothelial space, potentially leading to the development of atherosclerosis,” the authors write.

Triglyceride levels are usually measured in a fasting state, which would exclude most remnant lipoproteins; however, except for a few hours in the morning, most individuals are in a nonfasting state most of the time, they add.

“Therefore, by mainly studying fasting rather than nonfasting triglyceride levels, several previous studies may have missed an association between triglycerides and ischemic stroke,” Dr. Freiberg and colleagues write. “Also, because former studies mainly focused on moderately elevated levels of triglycerides, an association of very high levels with risk of ischemic stroke could have gone unnoticed.”

The current study used data on 13,956 men and women enrolled in the Copenhagen City Heart Study, a prospective, population-based study begun in 1976, with follow-up through July 2007. In this study, the researchers looked at baseline levels of nonfasting triglycerides, other risk factors at baseline and follow-up examinations, and the incidence of ischemic stroke.

They also carried out a cross-sectional study of 9637 participants in the prospective study who attended the 1991-1994 examination, since levels of nonfasting remnant lipoprotein cholesterol as well as the lipid profile were measured at that examination, the authors note. In the cross-sectional study, they looked at levels of nonfasting triglycerides, remnant cholesterol, and the prevalence of ischemic stroke.

Of the 13,956 participants in the prospective study, 1529 had an ischemic stroke during follow-up.” We observed an increased risk for ischemic stroke with increasing levels of nonfasting triglycerides, both in men and in women,” Dr. Freiberg told the meeting attendees (P for trend < .001 for both men and women).
After adjustment for conventional cerebrovascular risk factors, for age, body mass index, and diabetes, and finally adjusting for age and high-density lipoprotein cholesterol level, risk estimates were only attenuated slightly, Dr. Freiberg noted.

The absolute 10-year risk for 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 those with levels of 443 mg/dL and higher. The corresponding values for women were 1.9% and 12.2%.

In the cross-sectional study, they found nonfasting triglyceride levels were highest in those who had a previous ischemic stroke in both men and in women vs the control groups. Likewise, Dr. Freiberg noted, levels of remnant cholesterol were highest in those who developed ischemic stroke in both men and women.
“This led to the final conclusion that nonfasting triglycerides as a marker of remnant cholesterol were associated with increased risk of ischemic stroke, with the risk being 3 times higher in men and 4 times higher in women,” Dr. Freiberg concluded.

“People have missed this idea of thinking about triglycerides and remnants so there may be a key there for the future to prevent stroke, but we need a large, randomized, intervention trial,” he said.

He pointed out that although compounds like fibrates and nicotinic acid would be the best way to address high triglyceride levels, they are not very well tolerated by patients. Statins also reduce triglyceride levels to some degree as well as lowering low-density lipoprotein cholesterol levels, and could be a place to start. “Because there’s so much evidence that statins are good, I tend to favor using a statin to see how much you can lower triglycerides together with LDL if it’s not too high, and if that doesn’t work, then you can use the fibrates and nicotinic acid.”

Triglyceride levels are increased in those with higher body mass index and those with diabetes mellitus, he noted, but importantly, the risk associated with higher levels of nonfasting triglyceride levels seen in this study persisted after they stratified for body mass index.

Practice Pearls:

• A previous study demonstrated that higher levels of nonfasting triglycerides increased the risks for myocardial infarction and death among both women and men.
• In the current study, nonfasting triglyceride levels had a positive linear relationship with the risk for stroke among men and women.

The results are published in the November 12 issue of the Journal of the American Heart Association and were presented at the American Heart Association 2008 Scientific Sessions.