Recent studies have shown that individuals with 0 coronary artery calcium (CAC) scores have very low risk of coronary heart disease. In the Healthy Women Study, we evaluated development of new CAC among postmenopausal women (n=272) over a 6-year period, age 62 at the 1st and 68 at the 3rd electron beam tomography (EBT) examination. At the 1st EBT, 155 of 272 (57%) women had 0 CAC. By the 3rd, 56 (36%) of these women had developed new CAC, including 38 with >or=5 Agatston units. There was practically no regression from having CAC at the 1st EBT to no CAC at the 3rd EBT. The risk of developing new CAC over 6 years among women with 0 CAC on their 1st EBT was strongly and significantly related to presence of both aortic calcium and carotid plaque at the time of 1st EBT. Baseline premenopausal risk factors, age 47, apolipoprotein B, body mass index (BMI) and triglycerides, were significant predictors of incident CAC as were the changes in BMI and low density lipoprotein cholesterol between premenopause and the 1st post exam, age 53. Risk factors measured premenopause and change in risk factors from premenopause to the 1st post exam and the extent of subclinical disease in other vascular beds are primary determinants of the risk of developing incident CAC in women over a 6-year period.