The effect of
ciprofibrate treatment on the atherogenic profile of
low-density lipoprotein (
LDL) subspecies in combined
hyperlipidemia (CHL) has been investigated in six patients displaying elevated plasma
triglyceride and
cholesterol levels (> 200 and > 250 mg/dl, respectively). The E2E2 phenotype was excluded; four patients possessed familial antecedents of premature
coronary heart disease (CHD). Analysis of five
LDL subclasses separated by isopycnic density gradient ultracentrifugation showed a predominance of dense
LDL subspecies (
LDL-4 and
LDL-5, d 1.039-1.063 g/ml; 51% of total
LDL mass) in the asymmetric
LDL density profile characteristic of CHL patients at baseline.
Ciprofibrate treatment (100 mg/day for 1 month) effected marked reductions in both total plasma
LDL and
apo B-100 levels (approximately 19% and approximately 23%, respectively). Equally, the plasma profile of
LDL subspecies was normalised to a significant degree as a result of preferential reduction in the elevated levels of both dense subspecies (
LDL-4 and
LDL-5; -43% and -54%, respectively; P < 0.03 and P < 0.006 [corrected], respectively). The circulating concentrations of light
LDL (
LDL-1, d 1.019-1.023 g/ml) were also diminished significantly by
ciprofibrate (-30%; P < 0.006 [corrected]). Furthermore,
ciprofibrate not only effected reductions in the elevated
triglyceride content of the hydrophobic core of all
LDL subspecies but also normalised their common deficiency in free
cholesterol. In addition, the abnormally small particle diameters of LDL-4 and -5 were increased to normal. Plasma levels of both
apo B-100 and
triglycerides were significantly and positively correlated with those of LDL-4 and LDL-5, suggesting not only that the degree of
triglyceride elevation is intimately linked to the extent of shift in
LDL subclass profile towards denser subspecies, but also that
triglyceride reduction upon treatment strongly influences LDL-4 and LDL-5. In conclusion, our findings indicate that
ciprofibrate treatment in combined
hyperlipidemia results in marked reduction in plasma
triglyceride levels (-33%), and that such reduction is intimately linked to normalisation of both the qualitative and quantitative features of the atherogenic
LDL subspecies profile typical of this disorder.