The Great Importance of Nonfasting Triglycerides

July 28, 2008

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 The Great Importance of Nonfasting Triglycerides
CONTEXT: The association of triglycerides with incident cardiovascular disease remains controversial. Although triglyceride levels are typically obtained in the fasting state, postprandial hypertriglyceridemia may play an important role in atherosclerosis.

OBJECTIVE: To determine the association of triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 26,509 initially healthy US women (20,118 fasting and 6391 nonfasting) participating in the Women's Health Study, enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years. Triglyceride levels were measured in blood samples obtained at time of enrollment. MAIN

OUTCOME MEASURE: Hazard ratios for incident cardiovascular events (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death). RESULTS: At baseline, triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance. During a median follow-up of 11.4 years, 1001 participants experienced an incident cardiovascular event (including 276 nonfatal myocardial infarctions, 265 ischemic strokes, 628 coronary revascularizations, and 163 cardiovascular deaths), for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up. After adjusting for age, blood pressure, smoking, and use of hormone therapy, both fasting and nonfasting triglyceride levels predicted cardiovascular events. Among fasting participants, further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association (fully adjusted hazard ratio [95% confidence interval] for increasing tertiles of triglyceride levels: 1 [reference], 1.21 [0.96-1.52], and 1.09 [0.85-1.41] [P = .90 for trend]). In contrast, nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models (hazard ratio [95% confidence interval] for increasing tertiles of levels: 1 [reference], 1.44 [0.90-2.29], and 1.98 [1.21-3.25] [P = .006 for trend]). In secondary analyses stratified by time since participants' last meal, triglyceride levels measured 2 to 4 hours postprandially had the strongest association with cardiovascular events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P<.001 for trend]), and this association progressively decreased with longer periods of fasting.

CONCLUSIONS: In this cohort of initially healthy women, nonfasting triglyceride levels were associated with incident cardiovascular events, independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels showed little independent relationship.

From press release:

MedWire News: Two papers published in JAMA demonstrate that nonfasting triglyceride level is an important predictor of cardiovascular (CV) events.

“Triglycerides are routinely measured in the fasting state, excluding remnant lipoproteins; however, except for the first hours in the early morning, most individuals are in the nonfasting state most of the time,” say Børge Nordestgaard (Herlev University Hospital, Denmark) and colleagues, in their article.

But they say that remnant lipoproteins may play an important role in atherosclerosis, in which case, nonfasting triglyceride levels may reflect CV risk more accurately than do fasting levels.

The team found a strong association between nonfasting triglyceride levels and myocardial infarction (MI), ischemic heart disease, and death in 7587 women and 6394 men who were followed-up from baseline in 1976–1978 until 2004.

For example, compared with women with triglyceride levels lower than 1 mmol/l (88.5 mg/dl), the adjusted hazard ratios for MI rose from 1.7 in those with levels of 1–1.99 mmol/l (88.5–176.1 mg/dl) to 5.4 in those with levels of 5 mmol/l (442.5 mg/dl) or higher.

There was a similar association in men, and in both genders with respect to ischemic heart disease and death.

In their study, Sandeep Bansal (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and colleagues directly compared the predictive ability of nonfasting and fasting triglyceride levels in the 26,509 participants of the Women’s Health Study.

Compared with women in the first tertile of nonfasting triglyceride levels (<105 mg/dl; <1.2 mmol/l), those in the second (105–170 mg/dl; 1.2–1.9 mmol/l) and third (>170 mg/dl; >1.9 mmol/l) tertiles had adjusted hazard ratios of 1.44 and 1.98, respectively, for incident CV events, defined as MI, stroke, coronary revascularization, or CV death.

But fasting triglyceride levels did not predict CV events over the 11.4-year follow-up, at corresponding nonsignificant hazard ratios of 1.21 and 1.09.

In an accompanying editorial, Patrick McBride (University of Wisconsin School of Medicine and Public Health, Madison, USA) noted that “risk associated with elevated triglyceride levels may be more a function of the associated lipoprotein disorder than a direct numerical correlation with triglycerides.”

But he said that this is an irrelevant issue in clinical practice, as elevated triglyceride levels accurately reflect atherosclerosis risk, whether directly or indirectly.

McBride cautioned: “Post-prandial triglyceride levels may need to be measured under specific conditions to improve test reliability, which could add complexity to integrating this test into practice.”

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