195
Atherosclerosis, 31 (1978) 195-204 0 Elsevier/North-Holland Scientific Publishers, Ltd.
THE EFFECTS METABOLISM
OF PLASMA EXCHANGE
ON CHOLESTEROL
L.A. SIMONS, J. COREY GIBSON, J.P. ISBISTER and J.C. BIGGS Lipid Clinic and Haematology Department, University of NSW, Sydney (Australia)
St. Vincent’s Hospital and School of Medicine,
(Received 3 April, 1978) (Revised, received 20 June, 1978) (Accepted 22 June, 1978)
Summary Four patients heterozygous for familial hypercholesterolaemia were treated by repeated plasma exchange with or without lipid-lowering drugs. Repeated plasma exchange without drug therapy in 3 patients was associated with a significant l&-28% decrement in plasma cholesterol level, comparing control with plateau values observed 3 weeks after exchange. Further decrements in plateau values followed the addition of lipid-lowering drugs used in combination, clofibrate-nicotinic acid or clofibrate-nicotinic acid-cholestyramine (range of total decrement 39-5076). Plasma exchange was associated with an increased excretion of endogenous faecal steroids, but this increase was completely abolished by the subsequent administration of clofibrate-nicotinic acid. This therapy prevented any increase in bile acid excretion with concomitant use of cholestyramine resin. Plasma exchange with drug therapy was associated with a sustained rise in plasma cholesterol specific radioactivity. In a fourth patient, clofibrate-nicotinic acid was administered prior to plasma exchange and led to a 24% fall in plasma cholesterol. Subsequent plasma exchange in this patient produced no sustained change in plasma cholesterol plateau level. In two patients, withdrawal of drugs allowed plasma cholesterol to return to preexchange control levels. These observations suggest that plasma exchange probably produced an increase in endogenous cholesterol synthesis and a mobilisation of tissue cholesterol. In relation to plateau cholesterol values 3 weeks after an exchange, the data suggested that the reduction in plasma cholesterol level with plasma exchange and drug therapy could have been achieved by intensive drug therapy alone. Address for correspondence: Dr. L.A. Simons, Medical Professiorial Unit, St. Vincent’s Hospital, Darliwhurst, NSW 2010. Australia. This study was supported in part by grants from the National Heart Foundation of Australia and the National Health and Medical Research Council of Australia.
Clofibrate -- Faecal steroids ucid --Plasma c.rchar~gc
Key words:
Familial
hypcrcholesterolacrrlia
.- ~l’icwtinic
Introduction Repeated plasma exchange using the continuous flow blood cell separator has been suggested as a form of management for severe and resistant hypercholesterolaemia, particularly familial hypercholesterolaemia (FH) in the homozygous form [ 11. The more commonly seen heterozygotes for FH frequently have marked degrees of hypercholesterolaemia (> 13 mmol/l) which may also be resistant to conventional diet and drug therapy. Any acute fall in plasma cholesterol concentration with plasma exchange would be followed by compensatory changes, such as an increase in cholesterol and lipoprotein synthesis. However, this is difficult to document in the unsteady state [2]. The concomitant use of lipid-lowering drugs might prove therapeutically desirable, and might provide further insight into the metabolic effects of plasma exchange. This paper describes a two year evaluation of the effects of repeated plasma exchange with or without lipid-lowering drugs on cholesterol metabolism in four patients with FH in the heterozygous form. Methods Patients Clinical, biochemical and angiographic presented in Table 1. All patients appeared erozygous form, as judged by the presence increased levels of low density lipoprotein mata, premature coronary atheroscIerosis TABLE
data for the 4 patients studied are to be suffering from FH in the hetof marked hypercholesterolaemia, (LDL) cholesterol, tendon xanthoand similarly affected first degree
1
SUMMARY
OF
PRE-TREATMENT
CLINICAL
DATA
a -
Patient
Age
Sex
wt
RBW
Chol.
Trig.
(kg)
(%)
(mmol/l)
(mmolll)
Plasma 35
M
70
93
C0r0n.
Clinical
Angio.
LDL
11.1
9.4
1.6
Tendon
X,
C.A.D.
(2)
X.
C.A.D.
(3)
X.
C.A.D.
(3)
X,
N.D.
asymptomatic 55
F
66
116
13.9
12.1
1.5
Tendon angina
57
F
52
92
11.0
9.5
1.1
Tendon angina,
M . infarct 30
M
79
108
10.3
8.8
1.2
Tendon
asymptomatic a Abbreviations: nary done.
angiography;
RBW.
relative
C.A.D.
(3).
body
weight;
coronary
Chol., artery
Cholesterol; disease
(3
Trig., major
Triglycerides;
vessels);
Coron.
X = xanthomata;
Angio., N.D.
core= not
relatives. All patients had been diagnosed some years previously and had been consuming typical cholesterol lowering diets (polyunsat/sat >1.5 and
Atherosclerosis, 31 (1978) 195-204 0 Elsevier/North-Holland Scientific Publishers, Ltd.
THE EFFECTS METABOLISM
OF PLASMA EXCHANGE
ON CHOLESTEROL
L.A. SIMONS, J. COREY GIBSON, J.P. ISBISTER and J.C. BIGGS Lipid Clinic and Haematology Department, University of NSW, Sydney (Australia)
St. Vincent’s Hospital and School of Medicine,
(Received 3 April, 1978) (Revised, received 20 June, 1978) (Accepted 22 June, 1978)
Summary Four patients heterozygous for familial hypercholesterolaemia were treated by repeated plasma exchange with or without lipid-lowering drugs. Repeated plasma exchange without drug therapy in 3 patients was associated with a significant l&-28% decrement in plasma cholesterol level, comparing control with plateau values observed 3 weeks after exchange. Further decrements in plateau values followed the addition of lipid-lowering drugs used in combination, clofibrate-nicotinic acid or clofibrate-nicotinic acid-cholestyramine (range of total decrement 39-5076). Plasma exchange was associated with an increased excretion of endogenous faecal steroids, but this increase was completely abolished by the subsequent administration of clofibrate-nicotinic acid. This therapy prevented any increase in bile acid excretion with concomitant use of cholestyramine resin. Plasma exchange with drug therapy was associated with a sustained rise in plasma cholesterol specific radioactivity. In a fourth patient, clofibrate-nicotinic acid was administered prior to plasma exchange and led to a 24% fall in plasma cholesterol. Subsequent plasma exchange in this patient produced no sustained change in plasma cholesterol plateau level. In two patients, withdrawal of drugs allowed plasma cholesterol to return to preexchange control levels. These observations suggest that plasma exchange probably produced an increase in endogenous cholesterol synthesis and a mobilisation of tissue cholesterol. In relation to plateau cholesterol values 3 weeks after an exchange, the data suggested that the reduction in plasma cholesterol level with plasma exchange and drug therapy could have been achieved by intensive drug therapy alone. Address for correspondence: Dr. L.A. Simons, Medical Professiorial Unit, St. Vincent’s Hospital, Darliwhurst, NSW 2010. Australia. This study was supported in part by grants from the National Heart Foundation of Australia and the National Health and Medical Research Council of Australia.
Clofibrate -- Faecal steroids ucid --Plasma c.rchar~gc
Key words:
Familial
hypcrcholesterolacrrlia
.- ~l’icwtinic
Introduction Repeated plasma exchange using the continuous flow blood cell separator has been suggested as a form of management for severe and resistant hypercholesterolaemia, particularly familial hypercholesterolaemia (FH) in the homozygous form [ 11. The more commonly seen heterozygotes for FH frequently have marked degrees of hypercholesterolaemia (> 13 mmol/l) which may also be resistant to conventional diet and drug therapy. Any acute fall in plasma cholesterol concentration with plasma exchange would be followed by compensatory changes, such as an increase in cholesterol and lipoprotein synthesis. However, this is difficult to document in the unsteady state [2]. The concomitant use of lipid-lowering drugs might prove therapeutically desirable, and might provide further insight into the metabolic effects of plasma exchange. This paper describes a two year evaluation of the effects of repeated plasma exchange with or without lipid-lowering drugs on cholesterol metabolism in four patients with FH in the heterozygous form. Methods Patients Clinical, biochemical and angiographic presented in Table 1. All patients appeared erozygous form, as judged by the presence increased levels of low density lipoprotein mata, premature coronary atheroscIerosis TABLE
data for the 4 patients studied are to be suffering from FH in the hetof marked hypercholesterolaemia, (LDL) cholesterol, tendon xanthoand similarly affected first degree
1
SUMMARY
OF
PRE-TREATMENT
CLINICAL
DATA
a -
Patient
Age
Sex
wt
RBW
Chol.
Trig.
(kg)
(%)
(mmol/l)
(mmolll)
Plasma 35
M
70
93
C0r0n.
Clinical
Angio.
LDL
11.1
9.4
1.6
Tendon
X,
C.A.D.
(2)
X.
C.A.D.
(3)
X.
C.A.D.
(3)
X,
N.D.
asymptomatic 55
F
66
116
13.9
12.1
1.5
Tendon angina
57
F
52
92
11.0
9.5
1.1
Tendon angina,
M . infarct 30
M
79
108
10.3
8.8
1.2
Tendon
asymptomatic a Abbreviations: nary done.
angiography;
RBW.
relative
C.A.D.
(3).
body
weight;
coronary
Chol., artery
Cholesterol; disease
(3
Trig., major
Triglycerides;
vessels);
Coron.
X = xanthomata;
Angio., N.D.
core= not
relatives. All patients had been diagnosed some years previously and had been consuming typical cholesterol lowering diets (polyunsat/sat >1.5 and
