Tracking of coronary artery calcium (CAC) has been suggested for monitoring the effects of lipid control, but it is not known whether lipid control decreases progression of CAC. Seven hundred sixty-one subjects (mean age 64.5 +/- 7.3 years; 91% men; 69% positive for CAC) in an ongoing cohort study underwent baseline and follow-up (after 7.0 +/- 0.5 years) computed tomography for CAC. Subjects were stratified into low-risk (<2 risk factors), intermediate-risk (> or =2 risk factors but <20% risk of coronary heart disease over 10 years), or high-risk (> or =2 risk factors and >20% risk of coronary heart disease in 10 years or diabetes) groups. Lipid control was defined according to criteria of the National Cholesterol Education Program. Two-way analysis of covariance was used to examine the relation of low-density lipoprotein (LDL) cholesterol and risk group to change in CAC volume score. Control of levels of high-density lipoprotein (HDL) cholesterol and triglycerides was also examined in relation to progression of CAC. After adjustment for other risk factors and baseline CAC volume, CAC progression was similar between those with adequate and those with inadequate control of LDL cholesterol (p = 0.68) and across categories of optimal, intermediate, and higher risk LDL cholesterol (p = 0.40). However, higher levels of HDL cholesterol (> or =1.5 mmol/L [60 mg/dl]) were associated with less progression of CAC volume (151 vs 203 mm(3) in those with HDL cholesterol <1.0 mmol/L [40 mg/dl], p = 0.03). There was no relation between triglycerides and CAC progression (p = 0.54). Our findings do not support the use of CAC assessment for monitoring the control of LDL cholesterol, but greater progression of CAC may occur in those in whom HDL cholesterol is not controlled.