Abstract 187: Changes in High-Density Lipoprotein Cholesterol and Complement C3 are Strongly Inversely Correlated in the Setting of Niacin Therapy in Humans
Background Metabolic syndrome and other insulin resistant conditions are characterized by elevated fasting and post-prandial serum triglyceride (TG) levels. TG elevation may play a mechanistic role in the low HDL cholesterol (HDL-C) commonly found in these conditions, perhaps because TG-enriched HDL is more avidly catabolized. Complement C3 is the precursor of acylation stimulating protein, a hormone that stimulates TG storage in adipose. Fasting serum levels of complement C3 strongly positively correlate with post-prandial triglyceridemia. We hypothesized that upon niacin therapy increases in HDL-C would inversely correlate with decreases in complement C3 as a marker of improved post-prandial TG, and thus provide an indirect way to assess the linkage between post-prandial triglyceridemia and low HDL-C in patients with metabolic syndrome.
Methods We compared subjects before and after titration of open-label extended-release niacin to 2 grams daily, starting with 500 mg and adding 500 mg/week for the next 3 weeks, and returning after the 4th week. Fasting serum tests included lipoproteins by ultracentrifugation, and complement C3 by nephelometry. Using change in HDL-C as the dependent variable, we used Spearman’s correlation for univariate and regression for multivariable tests of association.
Results We evaluated 64 subjects, in whom HDL-C rose 8 mg/dL (+21%, p < 0.00005 vs. baseline). The change in HDL-C significantly inversely correlated with change in complement C3 (rho −0.38, p=0.0022). After multivariable adjustment, the change in complement C3 (p=0.003) remained a highly significant predictor of change in HDL-C.
Conclusion Niacin is the most effective drug available for raising HDL-C, though the mechanism of its HDL effect is largely unknown. The substantial inverse correlation with complement C3 is novel, and supports the hypothesis that HDL-C changes may reflect improved post-prandial triglyceridemia. This finding suggests that further study of niacin’s post-prandial effects would be fruitful to confirm this link, and to further validate complement C3 as a facile marker of post-prandial TG for future trials.