Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study

BMJ 1998;316:1127-1130 ( 11 April )

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Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study

Tatu A Miettinen, professor, ^a Helena Gylling, senior physician, ^a Timo Strandberg, assistant professor, ^a Seppo Sarna, associate professor, ^b for the Finnish 4S Investigators.

^a Department of Medicine, Division of Internal Medicine, University of Helsinki, FI-00290 Helsinki, Finland, ^b Department of Public Health, University of Helsinki

Correspondence to: Dr Miettinen tatu.a.miettinen{at}helsinki.fi

Objectives: To investigate whether baseline serum cholestanol:cholesterol ratio, which is negatively related to cholesterolsynthesis, could predict reduction of coronary events in the Scandinaviansimvastatin survival study.
Design: Follow up of patients with coronary heart disease in whom baseline ratios were related to major coronary events.
Setting: Four universities in Finland.
Subjects: A subgroup of 868 patients with coronary heart disease selected from the Scandinavian simvastatin survivalstudy.
Intervention: Treatment with simvastatin or placebo.
Main outcome measures: Serum concentrations of low density lipoprotein and high density lipoprotein cholesterol, totaltriglyceride concentration, and cholesterol:cholestanol ratio.Major coronary events.
Results: With increasing baseline quarter of cholestanol distribution the reduction in relative risk increased graduallyfrom 0.623 (95% confidence interval 0.395 to 0.982) to 1.166 (0.791to 1.72). The risk of recurrence of major coronary events increased2.2-fold (P<0.01) by multiple logistic regression analysis betweenthe lowest and highest quarter of cholestanol. The ratio of cholestanolwas related inversely to the body mass index and directly to highdensity lipoprotein cholesterol and triglyceride concentrationsbut their quarters of distribution were not related to risk reduction.
Conclusions: Measurement of serum cholestanol concentration revealed a subgroup of patients with coronary heart diseasein whom coronary events were not reduced by simvastatin treatment.Thus, patients with high baseline synthesis of cholesterol seemto be responders whereas those with low synthesis of cholesterolare non-responders.

Key messages

Recurrence of major coronary events is reduced by statin treatment in about one third of patients with coronary heart disease, to predict those who will not respond has not been possible from baseline lipid concentrations in the Scandinavian simvastatin survival.
This study showed that increasing quarters of cholestanol:cholesterol ratio, reflecting decreasing synthesis of cholesterol, were related to recurrence of major coronary events during simvastatin treatment in a Finnish subgroup (n=868) of the Scandinavian study.
The subjects with lowest baseline quarters of cholestanol were associated with significantly reduced relative risk of major coronary events, while the risk in the highest quarter was unchanged and 2.2 times higher than in the lowest one.
Cholestanol:cholesterol ratios were related inversely to the body mass index and directly to high density lipoprotein cholesterol and triglyceride concentrations, but their quarters were unrelated to risk reduction.
The findings suggest that patients with coronary disease who have high absorption (high basal cholestanol:cholesterol) and low synthesis of cholesterol do not benefit from statin treatment alone and that they can be identified by measuring serum cholestanol concentration before treatment.

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