ReviewPostprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants
Introduction
Due to the frequency of meal ingestion, individuals spend the majority of the day, approximately 18 h, in the fed (postprandial) state. The term given to the metabolic events that occur following the digestion and absorption of a meal that contains fat is postprandial lipemia. The magnitude and duration of the postprandial triglyceride (TG) response is influenced by a number of metabolic processes, including the rate of secretion of TG from the intestine and the liver, the activity of enzymes involved in the processing of TG-rich lipoproteins (TRLs; lipoprotein lipase (LPL) and hepatic lipase (HL)) and the rate of clearance of TRL remnants by receptor-mediated processes (Fig. 1).
It is now well established that the postprandial lipemic response is influenced by both the amount and type of dietary fat given in a test meal [1]. However, the postprandial TG response to a standardised fat-rich meal has been shown to be highly variable between individuals [2] and there is considerable interest in understanding both physiological and genetic determinants of the lipemic response and the mechanisms that underpin its impact on the progression of cardiovascular disease (CVD).
Section snippets
Fasting triglycerides, postprandial lipemia and cardiovascular disease risk
In 2007, Sarwar et al. [3] reported on the association between TG, predominately fasting, and risk of coronary heart disease (CHD), where original data from the EPIC-Norfolk (non-fasting TG) and Reykjavik studies were presented along with an updated meta-analysis which included 27 additional prospective studies. In the Reykjavik cohort, an age and gender adjusted odd ratios (OR) (95% confidence intervals) of 2.04 (1.78–2.32) was evident in those in the top vs. bottom tertile of fasting TG. An
The independence of triglycerides as a cardiovascular disease risk factor
Circulating TG is metabolically intimately linked with HDL; with elevated TG levels resulting in increased HL-mediated HDL hydrolysis and decreased HDL-C concentration. There is much ongoing debate regarding the independence of TG as a CVD risk indicator and its causal relevance, with many considering the impact of TG on CVD risk to be largely mediated through HDL-C. Consideration of the output from the three large prospective studies WHS, NCS and CCHS, provides insight into this discussion. In
Physiological mechanisms underlying the impact of postprandial lipemia on cardiovascular disease risk
Although, as discussed, a direct relationship between postprandial TG and CVD risk has now been established, the mechanisms by which TRLs exert their effect on the vascular wall are poorly understood. The sections below detail potential mechanisms of both lipid and non-lipid origin. Consensus is yet to be reached as to the effects of postprandial lipemia on some of these pathways, in particular inflammatory status and hemostasis where response to dietary TG is variable.
Acute impact of dietary fat amount and composition on the postprandial lipemic response
The postprandial lipemic response has been shown to be influenced by both the amount and type of dietary fat in the test meal [1]. Dose-dependent increases in the postprandial plasma TG response have been observed with single meals containing 30–50 g fat, with little difference in response with meals exceeding 80 g fat. The type of fat given in a meal has been shown to influence the fatty acid composition of chylomicron particles and the subsequent postprandial TG response [1]. Although
Regulation of postprandial lipemia by genetic factors
In 2007 [1] and 2008 [48], two expert reviews considered the available literature on lifestyle (acute and chronic composition of the diet, alcohol, exercise, smoking) and physiological determinants (age, gender, genotype, menopausal status, insulin sensitivity status, physical activity, adiposity) of the postprandial lipemic response. In the intervening years, numerous related publications have appeared in the literature, with an updated review published in 2010 [49]. The following discussion
Relative impact of common gene variants on postprandial lipemia compared to established regulators
Although Lopez-Miranda and co-authors attempted to compare the relative impact of the various factors thought to influence postprandial lipemia (Table 4 in the original paper), this was done in a semi-quantitative manner, with no consideration of potentially important gene variants [1]. In a preliminary univariate analysis of the DISRUPT cohort, higher TG AUC was evident in subjects in the 51–60 years vs. 20–40 years age range (27%), those with a BMI ≥ 25 kg/m2 vs. <25 kg/m2 (50%), men vs. women
Inflammation
In early clinical studies, the lipemic response to a high-fat meal was associated with a highly variable inflammatory response. In summarising this previously [26] we showed lipemia to both be associated with, or have little effect on, proinflammatory excursions and the conclusions were limited. Available studies now include overweight/obese, hypertriglyceridemic, MetS, and diabetic populations alongside healthy individuals. Whilst within-studies divergent responses remain [29], [35], [69], [70]
Vascular function and reactivity
Over the past decade, a number of studies have examined the effects of meal fatty acid composition on postprandial vascular reactivity (as summarised in [41]). Although the majority have shown the ingestion of moderate to high fat meals lead to a transient impairment in vascular function, the effects of different fatty acid classes are inconsistent. Whereas test meals rich in MUFA (refined olive oil and high-oleic sunflower oil) and SFA lead to a decrease in FMD, evidence is emerging to show
Closing remarks
The current review highlights the importance of non-fasting TG as a clinically significant CVD risk factor. It shows that, in addition to being lipid and lipoprotein mediated, the impact on disease risk is also likely to be mediated through adverse effects on inflammation, hemostasis and vascular function. In addition to LPL and apoE variants, apoA5 and FABP2 genotype are emerging as important genetic determinants of postprandial TG, with a potentially different impact in men and women. An
Author's contribution
The authors were involved in all aspects of the writing of the review article including decisions regarding the content and structure of the article.
Conflict of interest
None of the authors have any conflict of interest to report.
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