IJE Advance Access originally published online on September 10, 2007
International Journal of Epidemiology 2007 36(5):1060-1067; doi:10.1093/ije/dym169
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Is weak association between cigarette smoking and cardiovascular disease mortality observed in Japan explained by low total cholesterol?—NIPPON DATA80

1Department of Health Science, Shiga University of Medical Science, Shiga, Japan.
2Department of Hygiene and Preventive Medicine, Fukushima Medical University, Fukushima, Japan.
3Cardiovascular Epidemiology, Faculty of Home Economics, Kyoto Women's University, Kyoto, Japan.
4Department of Preventive Cardiology, National Cardiovascular Center, Osaka, Japan.
* Corresponding author. Department of Health Science, Shiga University of Medical Science, SetaTsukinowa –cho, Otsu 520-2192, Shiga, Japan. E-mail: ahozawa{at}belle.shiga-med.ac.jp
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Background An international comparison has indicated that the association between smoking and cardiovascular disease (CVD) differs according to total cholesterol (TC) levels. However, little has been published about the relationship between smoking and CVD mortality among populations with various cholesterol levels.
Methods We calculated the adjusted relative hazard (RH) of smoking for CVD mortality among 8912 Japanese individuals without a history of stroke or heart disease, who were separated according to TC levels of
5.40, 4.81–5.39, 4.26–4.80 and <4.25 mmol/l into groups Q4, Q3, Q2 and Q1, respectively. The P-values for multiple interactions between TC and smoking status for CVD mortality were calculated using TC as a continuous variable, dichotomized smoking status (never vs current), and by including cross-product terms in the regression models.
Results After 19 years of follow-up, 313 men and 291 women died of CVD. The RH of CVD mortality among men who currently smoked compared with those who never smoked was increased with higher TC (RH = 2.36 in Q4) and decreased in those with lower TC (RH = 0.85 in Q1) (interaction, P < 0.01). The profiles for coronary heart disease (CHD) mortality and ischaemic CVD (composite endpoint of CHD and ischaemic stroke) in men and for ischaemic CVD mortality in women were identical. The interaction might be explained by a biological mechanism and by frailty of those who have never smoked with lower TC.
Conclusions Counteractive measures should be implemented against smoking targeted towards Japanese with elevated TC levels.
Keywords Cigarette smoking, total cholesterol, cardiovascular diseases, interaction, prospective studies, Japan
Members of the NIPPON DATA Research Group are listed in the Appendix. Accepted 24 July 2007
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