Influence of serum amyloid A on the decrease of high density lipoprotein-cholesterol in active sarcoidosis.

OBJECTIVE

We have previously observed low levels of high density lipoprotein (HDL) cholesterol in active sarcoidosis. The aim of this study was to analyze the role of serum amyloid A (SAA) on this lipid disorder.

METHODS

Eighty five untreated sarcoid patients, 40 with active disease and 45 with inactive disease, were recruited. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL(2)-cholesterol, HDL(3)-cholesterol, apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and triglyceride concentrations. Serum amyloid A protein and lecithin-cholesterol acyltransferase (LCAT) activity were measured.

RESULTS

In active sarcoidosis we found significantly reduced levels of HDL-cholesterol (1.17+/-0.36 vs. 1. 44+/-0.39 mmol/l, P=0.002), HDL(3)-cholesterol (0.78+/-0.23 vs. 1. 02+/-0.21 mmol/l, P<0.0001), and apo A-I (1.36+/-0.29 vs. 1.61+/-0. 27 g/l, P<0.0001) and significantly increased levels of triglyceride (1.51+/-0.64 vs. 1.03+/-0.46 mmol/l, P<0.0001), and apo B (1.14+/-0. 25 vs. 0.99+/-0.27 g/l, P=0.012) versus inactive sarcoidosis. Serum amyloid A concentrations were significantly increased in the patients with active disease (155.45+/-154.01 mg/ml) compared to the inactive sarcoid patients (89.70+/-65.36 mg/ml) (P=0.011). There were no significant differences in cholesterol, LDL-cholesterol, HDL(2)-cholesterol or LCAT values between groups. Multivariate logistic regression analysis showed that HDL-cholesterol (regression coefficient b=-1.96; S.E.=0.87; P=0.02) and SAA (regression coefficient b=0.01; S.E.=0.004; P=0.01) were the two variables independently associated with disease activity. Moreover, a significant negative correlation was observed between SAA levels and both HDL-cholesterol (r=-0.39; P=0.01) and apo A-I (r=-0.35; P=0.03) levels, in the active sarcoid group. Conversely, no correlation was found in the inactive sarcoid group.

CONCLUSIONS

The low HDL-cholesterol and apo A-I concentrations seen in active sarcoid patients are associated with a significant increase of SAA levels. We suggest that the displacement of apo A-I by SAA on HDL accounts for the lower level of HDL-cholesterol seen in active sarcoidosis.