Biomarkers and risk factors of atherosclerosis among middle-aged men in an international population-based study

This manuscript examines three separate but inter-related research questions. After reviewing scientifically relevant literature in the first chapter, the second chapter compares the prevalence of carotid plaque among the three major race-ethnic groups in the Electron-beam computed tomography, Risk factor Assessment among Japanese and U.S. Men in the Post-World War II birth cohort (ERA JUMP Study). This study shows that carotid plaque, a biomarker of subclinical atherosclerosis, is significantly lower among men in Japan and South Korea than in the US. This difference is independent of traditional risk factors of coronary heart disease (CHD). Further, it shows that only age, hypertension and diabetes are cross-sectionally associated with the prevalence of carotid plaque.\ud The third chapter examines the association between brachial-ankle pulse wave velocity (baPWV) and coronary artery calcification (CAC), an established biomarker of coronary atherosclerosis and a strong predictor of future CHD risk. baPWV is a non-invasive and convenient measure of arterial stiffness and is clinically used in eastern Asia as a tool for assessing future cardiovascular risk. This study found that increasing baPWV is cross-sectionally associated with increasing prevalence of CAC among middle-aged men in the ERA JUMP study, including White men in the US.\ud The final and fourth chapter of the manuscript examines the association of serum levels of soy isoflavones and equol, with CAC among Japanese men in Japan. Japanese consume soy and soy products regularly. Isoflavones are a component in soy and are known to have anti-atherosclerotic properties. Equol is a potent isoflavone produced from the dietary isoflavone daidzein by action of intestinal bacteria. This study shows that individuals who have bacteria to convert daidzein to equol, i.e. equol producers, have lower CAC than equol non-producers.\ud These three studies, individually and as a whole, contribute significantly to the public health knowledge. Japan has significantly lower atherosclerosis than the US in spite of a similar level of risk factors. Several lessons may be learned from Japan in an effort to reduce CHD mortality in the US. baPWV may potentially provide similar information to clinicians as CAC without exposing the patient to radiation