title: Alcohol and coronary artery calcification: an investigation using alcohol flushing as an instrumental variable.
abstract: We examined whether alcohol flushing could be used as an instrumental variable (IV) and investigated the effect of alcohol consumption on coronary calcification using alcohol flushing status as an IV.
  
  
  
  We analysed cross-sectional data from 24 681 Korean adults (20 696 men and 3985 women) who had been administered a questionnaire assessing alcohol consumption and alcohol flushing, as well as a coronary artery calcium (CAC) measurement. The associations of alcohol flushing status with potential confounders and alcohol consumption were examined. We employed two-stage predictor substitution methodology for the IV analysis.
  
  
  
  The prevalence of alcohol flushing did not differ depending on gender, education, household income, cigarette smoking or physical activity. Balanced levels of confounders were observed between alcohol flushers and non-flushers. Alcohol flushing was closely related to alcohol consumption and levels of liver enzymes. In men, a doubling in alcohol consumption was associated with increased odds of coronary calcification in both the IV analysis [odds ratio (OR) of CAC scores of 1 or over = 1.11; 95% confidence interval (CI) = 1.03-1.20) and the multivariable regression analysis (OR = 1.04; 95% CI = 1.01-1.07). For cardiovascular risk factors, the IV analysis showed a positive association between alcohol consumption and blood pressure and high-density lipoprotein-cholesterol.
  
  
  
  Alcohol flushing can be used as an IV in studies evaluating the health impact of alcohol consumption, especially in East Asian countries. Through such an analysis, we found that increased alcohol consumption was associated with an increased risk of subclinical coronary atherosclerosis.
authors.affiliation: Center for Cohort Studies, Total Healthcare Center.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Yun
authors.affiliation: Center for Cohort Studies, Total Healthcare Center.|Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sung-Cheol
authors.initials: SC
authors.lastname: Yun
authors.affiliation: MRC Integrative Epidemiology Unit.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Center for Cohort Studies, Total Healthcare Center.|Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Epidemiology, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Department of Radiology.
authors.forename: Eun Chul
authors.initials: EC
authors.lastname: Chung
authors.affiliation: Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hocheol
authors.initials: H
authors.lastname: Shin
authors.affiliation: Department of Health Policy and Management, Seoul National University College of Medicine, and Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul, South Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Khang
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000208:ethnology*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000208:ethnology*; D003430:Cross-Sectional Studies; D005260:Female; D005483:Flushing / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D015995:Prevalence; D056910:Republic of Korea / Q000453:epidemiology
chemical_list: C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: ALDH2; Alcohol consumption; Mendelian randomization analysis; Republic of Korea; cardiovascular disease; coronary atherosclerosis