Concepcion Fiol

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. CONCLUSION 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.

Low levels of high density lipoprotein cholesterol in patients with active sarcoidosis

OBJECTIVE To determine lipoprotein abnormalities in patients diagnosed with sarcoidosis and their relation to disease activity. METHODS We studied 90 patients with biopsy-proven sarcoidosis who had not been treated with corticosteroids (44 with active disease and 46 with inactive disease) and 147 control subjects. 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, high density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apolipoprotein A-I, apolipoprotein B, and triglyceride concentrations. RESULTS Patients with active sarcoidosis had significantly low HDL-cholesterol concentrations (1.15 +/- 0.27 mmol/l) as compared with inactive sarcoid patients (1.40 +/- 0.34 mmol/l) and with the healthy control subjects (1.49 +/- 0.34 mmol/l) (p = 0.00001). The decrease in the HDL-cholesterol concentrations seen in patients with active disease was due mainly to the cholesterol bound to HDL2 subfraction. Apolipoprotein A-I concentrations were significantly reduced in the patients with active disease (1.18 +/- 0.32 g/l) compared to the healthy controls (1.38 +/- 0.27 g/l) (p = 0.003). There were no significant differences in cholesterol, triglyceride, LDL-cholesterol or apolipoprotein B values among the three groups. Multivariate logistic regression analysis showed that HDL-cholesterol was the only variable independently associated with disease activity (Regression Coefficient b = -0.03; S.E. = 0.008; p = 0.0005). CONCLUSION The decrease in HDL-cholesterol that is observed in patients with sarcoidosis is limited to those with active disease.

Improvement in endothelial dysfunction in patients with hypoalphalipoproteinemia and coronary artery disease treated with bezafibrate.

Summary: Isolated low high‐density lipoprotein cholesterol (HDLc) is a well‐known risk factor for cardiovascular disease and is associated with arterial endothelium dysfunction. Several studies have shown that cholesterol lowering in patients with hypercholesterolemia improves endothelial function, but the effect of treating low HDLc levels remains unknown. We studied the effect of increasing HDLc on endothelial function in patients with coronary artery disease (CAD) and isolated low HDLc (HDLc) <0.91 mM, low‐density lipoprotein cholesterol (LDLc) <4.1 mM, and triglycerides <2.8 mM. Flowmediated endothelium‐dependent dilatation (FMD) in response to reactive hyperemia was measured by brachial ultrasound, before and after bezafibrate treatment (400 mg daily for 6 months) in 16 patients with CAD and impaired FMD (<10%). After bezafibrate therapy, HDLc increased from 0.79‐1.0 mM (p = 0.0008) at the expense of both HDL2 and HDL3 subfractions, apolipoprotein A‐I increased from 1.04‐1.19 g/l (p = 0.0012), and fibrinogen decreased from 4.45‐3.39 g/l (p = 0.0007). The impaired FMD increased after bezafibrate treatment from a median of 2.5‐12.3% (p = 0.0004). Endothelial function was normalized in eight patients (50%), improved in four (25%), and did not change in four (25%). These observations indicate that in patients with isolated low HDLc and CAD, bezafibrate treatment improves endothelial function of brachial arteries, increases HDLc and apolipoprotein A‐I, and lowers fibrinogen concentrations.