Risk factors for stroke and lipid-lowering effect of pravastatin on the risk of stroke in Japanese patients with hypercholesterolemia: analysis of data from the MEGA Study, a large randomized controlled trial.

Author(s): Uchiyama S, Nakaya N, Mizuno K, Ohashi Y, Tajima N, Kushiro T, Teramoto T, Nakamura H, MEGA Study Group

Affiliation(s): Department of Neurology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. suchiyam@nij.twmu.ac.jp

Publication date & source: 2009-09-15, J Neurol Sci., 284(1-2):72-6. Epub 2009 May 6.

Publication type:

BACKGROUND: The aims of this study were to clarify the risk factors for stroke, and to investigate the effect of low-density lipoprotein cholesterol (LDL-C) lowering with pravastatin on the risk of stroke, in Japanese mild-to-moderately hypercholesterolemic patients enrolled in the MEGA Study. METHODS: Multivariate Cox proportional hazard model was used to determine the baseline risk factors for stroke. The proportion of treatment effect (PTE) explained by on-treatment LDL-C levels was estimated. RESULTS: In 7832 patients at risk, a total of 99 strokes were observed during the 5-year follow-up period. Significant relationships were observed between stroke and traditional risk factors such as male sex, advanced age, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a) (Lp[a]), hypertension, diabetes, obesity, and smoking. In the pravastatin group, hazard ratio (HR) for stroke adjusted by on-treatment lipid level was lower than the unadjusted value versus control (HR [95%CI], 0.48 [0.26-0.87] and 0.59 [0.38-0.92], respectively)--giving a negative PTE of -38.6% and suggesting that the risk reduction could not be explained by LDL-C lowering alone. CONCLUSIONS: Male sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin's LDL-C-lowering effect alone, suggesting pleiotropic effects.