Although the ratio of total to high-density lipoprotein cholesterol (TC/HDL) is a powerful predictor of cardiovascular disease (CVD), few studies have investigated which factors are associated with changes in this ratio over time. We examined predictors of a change in TC/HDL ratio over a period of 14 years among 4451 men free of CVD from the Physicians' Health Study.

Baseline and updated physician characteristics and CVD risk factors were included in multivariate linear and logistic regression models to determine factors associated with a change in the TC/HDL ratio or of having a ratio of ≥5 on follow-up.

After a mean follow-up of 14 years, mean total cholesterol decreased by 7 mg/dL, HDL increased by 1 mg/dL, and the ratio decreased by 0.37. In multivariate logistic analyses, physicians were more likely to have a TC/HDL ratio of ≥5 at follow-up if they maintained a weight of ≥25 kg/m² (OR, 1.69 [1.35 – 2.12]), gained weight (OR, 2.01 [1.55 – 2.62]), or became inactive (OR, 1.43 [1.11 – 1.83]). However, older physicians and those who consumed alcohol or received treatment for hyperlipidemia were more likely to have a ratio of <5.

Although pharmacologic treatment for hyperlipidemia had the greatest favorable impact on the ratio over time, our data also show that maintaining an ideal weight and exercise have beneficial effects. We therefore advocate a renewed fervor for raising public awareness of the benefits of healthy lifestyle behaviors and pharmacologic treatments that are associated with long-term maintenance of favorable cholesterol levels.