J Atheroscler Thromb, 2017; 24: 673-674. http://doi.org/10.5551/jat.ED068

Editorial

Sex Differences in the Association between Traditional Vascular Risk Factors and Subclinical Carotid Atherosclerosis in Taiwan Gen-Min Lin 1, 2, Yuichiro Yano 3, 4 and Satoshi Hoshide 4 1

Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan Departments of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 3 Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS, USA 4 Department of Cardiology, School of Medicine, Jichi Medical University, Tochigi, Japan 2

See article vol. 24: 677-686 Carotid intima – media thickness (cIMT) measured by B-mode ultrasound has been regarded as a good surrogate of subclinical carotid artery atherosclerosis since 1986 1). Numerous observational studies have since suggested that cIMT is predictive of many clinical cardiovascular diseases (CVDs), such as coronary heart disease and ischemic stroke. However, there were inconsistent results regarding whether cIMT can improve the prediction of CVD events beyond the traditional CVD risk factors in the general healthy populations 2). Statistical significance (e.g., hazard ratios) does not provide information about the effect size or the clinical relevance 3). As a result, in the American College of Cardiology and American Heart Association (2013) and European Society of Cardiology (2016) guidelines, cIMT is not recommended for routine measurement in clinical practice for CVD risk assessments. cIMT values may differ by race/ethnicity and sex. In general, blacks have greater cIMT than whites and Hispanics, and Asians have lower cIMT than other races 4). In addition, males have greater cIMT than females 4). These differences indicate that the burden of atherosclerosis varies across race or sex, and thus the study of cIMT needs race/ethnicity- and sex-specific approaches. In this issue of the Journal of Atherosclerosis and Thrombosis 5), Wu and colleagues examined the correlation between traditional CVD risk factors and cIMT — defined as the far-wall mean common carotid Address for correspondence: Gen-Min Lin, Department of Medicine, Hualien Armed Forces General Hospital, No.163, Jiali Rd., Xincheng Township Hualien, Taiwan E-mail: [email protected] Received: December 12, 2016 Accepted for publication: December 13, 2016

artery IMT — in 1,579 middle-to-old aged men and women in northern Taiwan. In the multivariable linear regression model, traditional CVD risk factors, including age, hypertension, fasting blood glucose, and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio, were correlated with cIMT in the overall cohort. As compared with females, the mean cIMT was greater in males and per 1.0 standard deviation (SD) increases of body mass index and LDL/HDL cholesterol ratio in males resulted in 0.0971 (p = 0.030) and 0.1177 (p = 0.0087) SD increase in cIMT, respectively. These findings suggested that the impact of metabolic abnormalities on cIMT might be less in females than males. The present study also revealed that the β coefficients of LDL/HDL cholesterol ratio and body mass index with cIMT decreased in participants who were free of common carotid artery plaques with or without prior clinical CVD, hypertension, and diabetes. A previous study has reported that inflammation in terms of elevated C-reactive protein concentration may modify the relationship between LDL and HDL and was associated with greater cIMT 6). Furthermore, high inflammation status may attenuate the association of LDL cholesterol concentrations with incident coronary heart disease in the elderly population 7). Notably, the proportion of cigarette smoking in males (48%) was much higher than that in females (7.6%) in the present study, which might result in higher inflammation status in males. As compared with the females, the weaker correlations of body mass index and LDL/HDL cholesterol ratio with cIMT in the males was likely affected by the potential confounder of inflammation status. In a previous Taiwanese study 8), Su and colleagues found that the association of LDL cholesterol and body mass index with cIMT was stronger in females than in males. Their findings contradicted the

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results of the present study. Shimabukuro and colleagues revealed that the component of sex difference may differ within Japan as well 9). As stated in the present study, these inconsistent findings may be due to differences in the prevalence of the traditional CVD risk factors and lifestyle among different populations. Furthermore, the cross-sectional design of our study is not appropriate to translate the findings to the temporal relationship. Unexpectedly, Huang and colleagues have shown that body mass index and hypercholesterolemia were not predictive of cIMT progression in males or females in Taiwan 10). In summary, we did not have sufficient data for determining sex-specific temporal relationship between traditional CVD risk factors and cIMT in the general populations in Taiwan, and further investigation is required. Conflict of Interests None. References 1) Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation, 1986; 74: 1399-1406 2) Robertson CM, Gerry F, Fowkes R, Price JF. Carotid intima-media thickness and the prediction of vascular events. Vasc Med, 2012; 17: 239-248 3) Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circula-

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tion, 2010; 121: 1768-1777 4) Kim C, Diez-Roux AV, Nettleton JA, Polak JF, Post WS, Siscovick DS, Watson KE, Vahratian AM. Sex differences in subclinical atherosclerosis by race/ethnicity in the multi-ethnic study of atherosclerosis. Am J Epidemiol, 2011; 174: 165-172 5) Wu TW, Hung CL, Liu CC, Wu YJ, Wang LY, Yeh HI. Associations of cardiovascular risk factors with carotid intima-media thickness in middle-age adults and elders J Atheroscler Thromb, 2017; 24: 677-686 6) Peters MJ, van Halm VP, Nurmohamed MT, Damoiseaux J, Tervaert JW, Twisk JW, Dijkmans BA, Voskuyl AE. Relations between autoantibodies against oxidized lowdensity lipoprotein, inflammation, subclinical atherosclerosis, and cardiovascular disease in rheumatoid arthritis. J Rheumatol, 2008; 35: 1495-1499 7) Whelton SP, Roy P, Astor BC, Zhang L, Hoogeveen RC, Ballantyne CM, Coresh J. Elevated high-sensitivity C-reactive protein as a risk marker of the attenuated relationship between serum cholesterol and cardiovascular events at older age. The ARIC Study. Am J Epidemiol, 2013; 178: 1076-1084 8) Su TC, Chien KL, Jeng JS, Chen MF, Hsu HC, Torng PL, Sung FC, Lee YT: Age- and gender-associated determinants of carotid intima-media thickness: a communitybased study. J Atheroscler Thromb, 2012; 19: 872-880 9) Shimabukuro M, Hasegawa Y, Higa M, Amano R, Yamada H, Mizushima S, Masuzaki H, Sata M: Subclinical Carotid Atherosclerosis Burden in the Japanese: Comparison between Okinawa and Nagano Residents. J Atheroscler Thromb, 2015; 22: 854-868 10) Huang LC, Lin RT, Chen CF, Chen CH, Juo SH, Lin HF: Predictors of Carotid Intima-Media Thickness and Plaque Progression in a Chinese Population. J Atheroscler Thromb, 2016; 23: 940-949

Sex Differences in the Association between Traditional Vascular Risk Factors and Subclinical Carotid Atherosclerosis in Taiwan.

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