Assessment of long-term plasma exchange for familial hypercholesterolaemia.

Abstract

suMMARY The effectiveness of repeated plasma exchange with 2 to 4 litres of plasma protein fraction as long-term treatment for familial hypercholesterolaemia has been evaluated in six severely affected patients receiving conventional cholesterol lowering treatment. Cell-separator mediated exchange at monthly intervals for one to two years reduced mean serum cholesterol levels from 18 5 mmol/I (715 mg/dl) to 12-4 mmol/l (480 mg/dl) in two female homozygotes but failed to influence xanthomata or prevent a two-to threefold increase in their left ventricular aortic systolic pressure gradients. More effective reduction of mean serum cholesterol levels from 15 7 mmol/l (608 mg/dl) to 8-6 mmol/l (333 mg/dl) in two male homozygotes by plasma exchange at fortnightly intervals for two to three years was accompanied by resolution of xanthomata and by stabilisation of aortocoronary lesions. In two male heterozygotes with angina, coronary angiographic appearances were unaltered or improved after one to two years of thrice-monthly plasma exchange, which reduced mean serum cholesterol levels from 6-4 mmol/I (248 mg/dl) to 4 7 mmol/I (182 mg/dl). We conclude that plasma exchange every one to two weeks, combined with oral nicotinic acid and/or cholestyramine, retards the rate of progression of atheroma in homozygotes and possibly induces regression in heterozygotes.Familial hypercholesterolaemia is a dominantly inherited defect of beta-or low-density lipoprotein metabolism which affects approximately 1 in 500 persons in Britain' and North America.2 The great majority of affected subjects are heterozygotes in whom the disorder is characterised by hyperbetalipoproteinaemia (type II hyperlipoproteinaemia) from birth, appearance of tendon xanthomata in early adult life, and the premature onset of coronary heart disease. Men

Selective removal of low density lipoprotein by plasmapheresis in familial hypercholesterolemia.

“…Figure 5 shows several LDL peaks, which were mostly caused by a long interval of nontreatment due to the holidays. Considering the timecourse of the increase of LDL after the treatment, 10 '** we find that the average concentraton of LDL is a little higher than the midpoint of the values before and after treatment. It is, therefore, probably 280 mg/dl to 300 mg/dl for Case 3 and 300 mg/dl to 320 mg/dl for Case 4.…”

Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia.

“…This type of hyperlipidemia, in the homozygous form, is refractory to the conventional lipid-lowering treatments and leads to premature development of atherosclerotic cardiovascular disease.1 Nonpharmacologic treatments that have been proposed for the management of patients with familial hypercholesterolemia include plasma exchange2 and LDL apheresis.3-7The aim of these treatments is to produce a marked and sustained cholesterol-lowering effect to retard progression or induce regression of atheromatous plaques. 8 There is evidence that blood flow to the lower limbs is enhanced by the procedure of plasma exchange. 9 The time course of this effect is unrelated to changes in plasma cholesterol; the improvement in blood flow to the lower limbs is possibly explained by the simultaneous removal of several plasma constituents leading to reduced plasma and total blood viscosity.10 Moreover, simultaneous improvement of the rheologic properties of erythrocytes has been suggested.1' For most of the studies, only short-term data are available, and little is known concerning the effects of repeat procedures.…”

Ten-year Follow-up of Familial Hypercholesterolemia Patients After Intensive Cholesterol-lowering Therapy

“…Currently, intensive lipid-lowering therapy with extracorporeal elimination of serum LDL cholesterol (LDL-apheresis) is applied to FH patients. LDL apheresis is suggested to reduce coronary atherosclerosis, [1][2][3][4][5][6] and also to improve regional myocardial perfusion, exercise tolerance, and ischemic symptoms. 4) These effects result from an improvement in endothelial nitric oxide (NO) production, [7][8][9][10] endothelial adhesiveness, 11,12) and blood rheology.…”