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.
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.
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
Shinichiro
S
Uchiyama
Noriaki
N
Nakaya
Kyoichi
K
Mizuno
Yasuo
Y
Ohashi
Naoko
N
Tajima
Toshio
T
Kushiro
Tamio
T
Teramoto
Haruo
H
Nakamura
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood; D003131:Combined Modality Therapy; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy* / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D017270:Lipoprotein(a) / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D017035:Pravastatin / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D002784:Cholesterol; D017035:Pravastatin