Cardiovascular risk factor clustering and ratio of total cholesterol to high-density lipoprotein cholesterol in angiographically documented coronary artery disease. High levels of cardiac risk factors tend to cluster together and act synergistically. To develop a suitable and practical marker for clustering, we evaluated 380 consecutive patients at the time of coronary angiography. Analyses of lipid, rheologic, clinical and arteriographic profiles indicated a variety of interwoven relations. Because the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (total/HDL cholesterol) was closely related to both the presence and extent of greater than or equal to 50% diameter reduction of greater than or equal to 1 coronary arteries, it was used to divide patients into quartiles. Clustering of high- and low-level risk factors was demonstrated in the highest and lowest quartiles of total/HDL cholesterol, respectively (p less than 0.001). The highest quartile may be characterized by an only moderately elevated total cholesterol level but patients in this quartile may have a very low HDL cholesterol level, high triglycerides, a tendency toward high hemoglobin and fibrinogen levels, a history of smoking, previous myocardial infarction and multivessel disease. These results suggest that total/HDL cholesterol serves as a marker not only for obstructive coronary disease but also for a cluster of potentially modifiable risk factors. 