MSI Newsletter - March 2008

Fasting triglyceride levels show little independent association

The importance of triglycerides in cardiovascular risk is controversial. Triglycerides are typically determined in the fasting state, yet postprandial hypertriglyceridaemia may play an important role in atherosclerosis. This study sought to determine the association of fasting versus nonfasting triglyceride levels and risk of future cardiovascular events. Controversy surrounds the role of triglycerides in cardiovascular disease, in part because the relation between the two is attenuated by adjustment for high-density lipoprotein (HDL)cholesterol, levels of which are inversely correlated with triglyceride levels. Also, triglyceride levels are usually measured in the fasting state, whereas postprandial lipids seem to play an important part in the pathogenesis of cardiovascular disease. In this study, Bansal et al assessed the association of fasting and nonfasting triglyceride levels with incident cardiovascular events in a prospective cohort of initially healthy women, independently of classic cardiac risk factors, other lipid levels, and insulin resistance markers.

Study population, design and measurements

This prospective study involved 26,509 initially healthy women participating in the US Women’s Health Study (enrolled between November 1992 and July 1995) followed up for a median 11.4 years. Blood samples collected at enrollment were used for triglyceride determination. Participants whose last meal was at least 8 hours prior to blood sample collection were taken as the fasting cohort (n=20,118), while those who had eaten within 8 hours of blood sampling constituted the nonfasting cohort (n=6,391).The main outcome measure was hazard ratios for incident cardiovascular events, which were a composite of nonfatal myocardial infarction, coronary revascularization, nonfatal ischaemic stroke, or cardiovascular death. An end points committee adjudicated all cardiovascular events, and if a participant had more than one event, only the first was used in the analysis.

Results

A total of 1,001 participants had a first cardiovascular event during a median follow-up of 11.4 years, which corresponds to an overall event rate of 3.46 per 1000 person-years of follow-up. After adjustment for age, smoking, blood pressure, and use of hormone therapy (which increases triglyceride levels by about 20%), both fasting and nonfasting triglyceride levels were strongly associated with cardiovascular events (see Figure).The association between triglyceride levels and cardiovascular events among fasting participants was substantially weakened following adjustment for total cholesterol and HDL-cholesterol, and for indicators of insulin resistance (diabetes mellitus, body mass index, C-reactive protein). In contrast, the strong association with cardiovascular events in the nonfasting participants persisted after full adjustment. Secondary analyses stratified by time since the participants’ last meal showed that the strongest association of cardiovascular events was with triglyceride levels measured 2 to 4 hours postprandially (fully adjusted hazard ratio [95% confidence interval] for highest versus lowest tertiles of levels = 4.48 [1.98-10.15] [P<0.001 for trend]). Longer periods of fasting attenuated this association. Because of data suggesting that adjustment for HDL-cholesterol substantially alters the relation between cardiovascular disease and triglycerides, the authors repeated their analyses stratified by HDL-cholesterol level. Only high nonfasting triglyceride levels were independently associated with events in participants with normal HDL-cholesterol (50 mg/dL). High levels of triglycerides increased risk in both fasting and nonfasting women with HDL-cholesterol <50 mg/dL, but the magnitude of the effect was greater in the nonfasting group.

Conclusion

The authors argue that their data provides support for the broad hypothesis that atherosclerosis is at least partly a “postprandial phenomenon”. In addition to this putative atherogenic effect of postprandial lipids, high triglyceride levels are also a manifestation of the constellation of metabolic derangements associated with insulin resistance and the metabolic syndrome.The data reported in this article are consonant with prior cross-sectional studies correlating postprandial levels with severity of carotid atherosclerosis, and with case-control studies that indicate higher postprandial levels among individuals with coronary heart disease. The authors believe that fasting levels of triglycerides may not be the best marker for atherogenicity associated with hypertriglyceridaemia, and suggest that nonfasting levels constitute a more reliable criterion for participant inclusion in future trials of triglyceride-lowering agents.