INFORME TÉCNICO

Fasting TG levels are a strong predictor o f postprandial lipaemia, and many studies have reported significant positive correlations between fasting TGs and the total TG response during the postprandial period (e.g. Mattock et al. 1981, Patsch et al. 1983, 1992, Patsch 1987, Weintraub et al. 1987, Cohn et al. 1988, Simpson et al. 1990, Groot et al. 1991, O ’Meara et al. 1992). The correlation coefficient (extent o f covariance between two interdependent variables) can be as high as 0.93 (Syvanne et al. 1994). This explains the decline of interest in postprandial lipid metabolism in the 1960s; fasting TG levels were strongly related to postprandial TG levels and to the rate o f disappearance o f chylomicrons

(Nestel 1964, Pelkonen & Nikkila 1965). Interest was revived when the two variants o f apoB, apoB-48 and apoB-100 were discovered (Kane et al. 1980). The inverse association o f fasting TG levels and the rate of chylomicron metabolism (Nestel 1964) led to the speculation that impaired chylomicron TG clearance reflects a competition o f chylomicrons with VLDL for removal (Grundy & Mok 1976), since both compete for the action o f LPL (Brunzell et al. 1973). This is supported by the finding o f an inverse correlation between magnitude o f postprandial lipaemia and post-heparin activity o f LPL (Patsch 1987, W eintraub et al. 1987).

In studies o f normolipidaemic individuals, LPL activity and HDL-cholesterol were strongly inversely related to postprandial TG response in the chylomicron fraction (Weintraub et al. 1987) and to magnitude of postprandial lipaemia (Mowri et al. 1994), in line with current concepts on the direct relationship between rates o f chylomicron metabolism and transfer o f surface components to HDL (Patsch et al. 1983, Eisenberg 1984). In studies of patients, there was no relationship between LPL activity and magnitude o f postprandial lipaemia e.g. in middle-aged CAD patients (Groot et al. 1991), or in NIDDM (non-insulin- dependent diabetes mellitus) individuals (Syvanne et al. 1994), implying an abnormality in lipolysis o f TG-rich lipoproteins in these groups of individuals. The relation between LPL activity and postprandial lipaemia may therefore depend on several factors; the lipoprotein fraction being considered, LPL activity, age, obesity and insulin resistance (Miesenbock & Patsch et al. 1992) and presence/absence o f hyperlipoproteinaemia (Weintraub et al. 1987) and NIDDM (Syvanne et al. 1994).

Strong inverse correlations between HDL (in particular HDLg) in a number o f studies (eg. Patsch et al. 1983, 1984, Patsch 1987) or apoAI levels (Patsch et al. 1983) and magnitude o f postprzindial lipaemia have been reported. The relationship between HDL- cholesterol & HDL2 and postprandial TG response appears to be stronger than that between HDL (or HDL2) and fasting TGs (Patsch et al. 1983, 1984), leading to the proposal that low HDL-cholesterol concentrations in normolipidaeic men are caused by latent defects in TG metabolism which become apparent only upon challenge with a dietary fat load (Patsch et al.

1984) but these appear not to include defective clearance o f chylomicron remnants (Cohen et al. 1992). The inverse correlation between HDL and Sf 60-400 postprandial lipoproteins

was stronger than that between HDL and Sf 20-60 postprandial lipoproteins (Karpe et al. 1993b). However this inverse relationship between postprandial lipaemia and HDL-chol levels appears to be weaker in NIDDM patients (Syvanne et al. 1993, 1994), endurance- trained men (Cohen et al. 1991) and in individuals with hypoalphalipoproteinaemia and mild HTG (Ooi et al. 1992). Characteristics such as age, obesity and fasting lipid concentrations may distort the metabolic interactions, and thus weaken the inverse relationship, between TG- rich lipoproteins and HDL. Plasma levels o f LpAI (HDL particles containing only apoAI; H D L2 is comprised mainly of these), but not LpAI: A ll (HDL particles containing both apoAI and apoAII) w ere inversely related to magnitude o f postprandial lipaemia in normolipidaemic individuals (Mowri et al. 1994). This seems to be explained by the differential associations between LpAI or LpAI: A ll and lipoprotein modifying enzymes; LpAI levels were postively associated with LPL activity and inversely associated with HL activity (Mowri et al. 1994).

H L activity is a moderate positive determinant of postprandial lipaemia (Patsch 1987, Syvanne et al. 1994). In normotriglyceridaemic individuals, HL activity is inversely related to levels o f chylomicrons and their remnants (Weintraub et al. 1987). HL activity was negatively correlated with the postprandial TG response in the IDL fraction in NIDDM individuals (Syvanne et al. 1993) compatible with the putative role o f HL in IDL catabolism in hyperlipidaemia (Taskinen & Kuusi 1987). Hyperlipidaemia (partly due to VLDL-TG overproduction) is a characteristic o f NIDDM (Taskinen 1990).

Postprandial lipaemia is associated postively with fasting levels o f apoB (Patsch et al. 1983, Patsch & Gotto 1987). Dyslipidaemias which are characterised by elevated fasting apoB levels, such as FCHL (Grundy et al. 1987) and LCAT deficiency (Murano et al. 1987) - see Section 1.8.3, are also associated with elevated postprandial lipaemia. M ore recently the TG-rich lipoprotein response to an oral fat load was positively correlated with concentration o f apoB in dense LDL. Dense protein-rich LDL is a characteristic o f patients with manifest CHD (Sniderman et al. 1982, Swinkels et al. 1989, Tom vail et al. 1991, Coresh et al. 1992) and a preponderance o f small LDL particles is linked to increased risk o f MI (Austin et al. 1988) and presence o f CAD (Campos et al. 1992).

postprandial lipaemia in individuals with CAD or NIDDM or healthy controls (Syvanne et al. 1994). This is consistent with findings that elevated insulin levels (e.g. Eschwege et al. 1985) are an independent predictor o f atherosclerosis and that patients with atherosclerosis have exaggerated postprandial lipaemia (see Section 1.8.3). Cross-sectional studies have shown that NIDDM patients with atherosclerosis have higher fasting plasma levels o f insulin than do those without atherosclerosis (eg. Hillson et al. 1984) and hyperinsulinaemia is an indicator o f CAD in both NIDDM patients and non-diabetic subjects (Ronnemaa et al. 1991). Insulin resistance (functional insulin deficiency), as in NIDDM, leads to increases in plasma TGs and free fatty acids levels (Reaven & Reaven 1974). The main abnormality in NIDDM is in the removal o f TG-rich lipoproteins, which is partially due to a decrease in LPL activity in adipose tissue (Chen et al. 1979). Insulin is a known positive regulator o f adipose tissue LPL activity (Tavangar et al. 1991 and see Section 1.6.3) and in insulin resistance, hepatic TG-rich lipoprotein overproduction superimposed on reduced lipolysis of chylomicrons and VLDLs will augment postprandial lipaemia (Patsch et al. 1986).

Section 1.8.3 Relationship of postprandial lipaemia with presence and severity of