Oral carbocisteine does not lower serum lipoprotein(a) levels

Atherosclerosis, 90 (1991) 219-220 0 1991 Elsevier Scientific Publishers ADONIS 002191509100182E

ATHERO

219 Ireland,

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04721

Letter to the Editors

Oral carbocisteine does not lower serum lipoprotein(a) A.D. MBewu,

P.N. Durrington,

D. Bhatnagar,

levels

J.P. Miller and M.I. Mackness

Department of Medicine, University of Manchester, Manchester Royal Infirmary, Manchester Ml3 9WL (U.K.) (Received 29 July, 1991) (Accepted 5 August, 1991)

Dear Sirs,

with N-acetylcysteine (NAC). Stalenhoef and colleagues observed no, or very small, reductions in plasma Lp(a> levels in 19 subjects treated with NAC. NAC has a free sulphydryl group, and, it was suggested, might lower serum Lp(a) concentration by reductively cleaving the cysteine disulphide bridge between apolipoproteinta) (apota))

Serum lipoprotein(a) (Lp(a)> is a marker for early-onset coronary heart disease and has structural properties which would implicate it in both atherogenesis and thrombogenesis [1,2]. Dr. Gavish and colleagues [3] recently reported a decrease in serum Lp(a) levels in 2 patients treated

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2

1

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20

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Fig. 1. Serum Lp(a) concentration

in 5 healthy

Correspondence to: Dr. P.N. Durrington, Medicine, The University of Manchester, Royal Oxford Road, Manchester Ml3 9WL, U.K.

subjects

Dept. of Infirmary,

taking carbocisteine,

1500 mg daily for 2 weeks.

220

and apolipoprotein B (ape B) in the Lp(a) particle. The ape(a) released might then undergo more rapid catabolism than the whole Lp(a) particle. Scanu [5] observed a decline in immunoreactivity of Lp(a) after incubation with NAC. This was considered to be due to structural changes in the kringle domains that followed cleavage of the disulphide bonds, suggesting an alternative immunological mechanism by which Lp(a) might be decreased by NAC. We set out to discover if carbocisteine, an agent related to NAC, which is more palatable to take orally, might also reduce serum Lp(a) levels. The study was approved by the Clinical Medical Ethical Committee of the Royal Infirmary, Manchester. Five healthy volunteers were recruited. Blood was taken for baseline serum Lp(a) estimation on two occasions before starting oral carbocisteine syrup, 10 ml (500 mg), 3 times daily for 2 weeks. Serum Lp(a) was measured using an immunoradiametric assay (IRMA) from Pharmacia (Uppsala, Sweden), which shows almost no cross-reactivity with plasminogen [61. There was no significant change in the geometric mean serum Lp(a) concentration as assessed by analysis of variance (ANOVA) and by paired t-test comparing the baseline serum Lp(a) with the lowest level during treatment (Fig. 1).

Carbocisteine differs from NAC in that its sulphydryl group is blocked. Thus a free sulphydryl group may be necessary in an agent that is required to reduce serum Lp(a) levels. Agents with free sulphydryl groups tend to be unpalatable or toxic. It would be useful to try captopril, an angiotensin converting enzyme inhibitor, as this has a free sulphydryl group. It is also possible that the earlier report by Gavish et al. [3] based on only 2 patients was fortuitous since a similar study using NAC [4] gave results as disappointing as ours with carbocisteine.

References 1 MBewu, A.D. and Durrington, P.N., Lipoprotein (a): structure, properties and possible involvement in thrombogenesis and atherogenesis (review), Atherosclerosis, 85 (1990) 1. 2 Editorial, Lipoprotein (a), Lancet, i (1991) 397. 3 Gavish, D. and Brelow, J.L., Lipoprotein(a) reduction ny N-acetylcysteine, Lance& 337 (1991) 203. 4 Stalenhoef, A.F.H., Kroon, A.A. and Demacker, P.N.M., N-Acetylcysteine and lipoprotein, Lancet, 337 (1991) 491. 5 Scanu, A.M., N-Acetylcysteine and immunoreactivity of lipoprotein(a), Lancet, 337 (1991) 1159. 6 Durrington, P.N., Ishola, M., Hunt, L., Arrol, S. and Bhatnagar, D., Apolipoprotein (a), Al, and B and parental history in men with early onset ischaemic heart disease, Lancet, i (1988) 1070.