Patient-Level Discordance in Population Percentiles of the Total Cholesterol to High-Density Lipoprotein Cholesterol Ratio in Comparison With Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol: The Very Large Database of Lipids Study (VLDL-2B)

Abstract

Background: The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, estimated low-density lipoprotein cholesterol (LDL-C), and non-HDL-C are routinely available from the standard lipid profile. We aimed to assess the extent of patient-level discordance of TC/HDL-C with LDL-C and non-HDL-C, because discordance suggests the possibility of additional information.

Methods and results: We compared population percentiles of TC/HDL-C, Friedewald-estimated LDL-C, and non-HDL-C in 1 310 432 US adults from the Very Large Database of Lipids. Lipid testing was performed by ultracentrifugation (Vertical Auto Profile, Atherotech, AL). One in 3 patients had ≥25 percentile units discordance between TC/HDL-C and LDL-C, whereas 1 in 4 had ≥25 percentile units discordance between TC/HDL-C and non-HDL-C. The proportion of patients with TC/HDL-C > LDL-C by ≥25 percentile units increased from 3% at triglycerides <100 mg/dL to 51% at triglycerides 200 to 399 mg/dL. On a smaller scale, TC/HDL-C > non-HDL-C discordance by ≥25 percentile units increased from 6% to 21%. In those with <15th percentile levels of LDL-C (<70 mg/dL) or non-HDL-C (<93 mg/dL), a respective 58% and 46% were above the percentile-equivalent TC/HDL-C of 2.6. Age, sex, and directly measured components of the standard lipid profile explained >86% of the variance in percentile discordance between TC/HDL-C versus LDL-C and non-HDL-C.

Conclusions: In this contemporary, cross-sectional, big data analysis of US adults who underwent advanced lipid testing, the extent of patient-level discordance suggests that TC/HDL-C may offer potential additional information to LDL-C and non-HDL-C. Future studies are required to determine the clinical implications of this observation.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01698489.

Keywords: cholesterol; lipids; lipoproteins; primary prevention.

© 2015 American Heart Association, Inc.

Figures

Figure 1

Patient-level discordance between population percentiles of TC/HDL-C and LDL-C. Population percentiles of TC/HDL-C and LDL-C are presented on this plot for the whole population (A) and for four different triglyceride categories (B). Points to the left of the diagonal line represent individuals with TC/HDL-C percentile > LDL-C percentile and points to the right of the diagonal line represent individuals with TC/HDL-C percentile < LDL-C percentile. The density of data is expressed by different shades of color, which represent increasing densities of patients per pixel, from light blue to purple. The number next to each color on the color axis represents the maximum number of patients per pixel of this color. ρ is Spearman correlation coefficient. TC/HDL-C (Total Cholesterol to HDL-C ratio); LDL-C (Low-density Lipoprotein Cholesterol).

Figure 2

Patient-level discordance between population percentiles of TC/HDL-C and non-HDL-C. Population percentiles of TC/HDL-C and non-HDL-C are presented on this plot for the whole population (A) and for four different triglyceride categories (B). Points to the left of the diagonal line represent individuals with TC/HDL-C percentile > non-HDL-C percentile and points to the right of the diagonal line represent individuals with TC/HDL-C percentile < non-HDL-C percentile. The density of data is expressed by different shades of color, which represent increasing densities of patients per pixel, from light blue to purple. The number next to each color on the color axis represents the maximum number of patients per pixel of this color. ρ is Spearman correlation coefficient. TC/HDL-C (Total Cholesterol to HDL-C ratio); non-HDL-C (Non-High-density Lipoprotein Cholesterol).

Figure 3

3-D plot of the extent of discordance between TC/HDL-C, LDL-C and non-HDL-C percentiles across different percentile units thresholds. On the X-axis, we present discordance between TC/HDL-C and LDL-C percentiles, TC/HDL-C and non-HDL-C percentiles and LDL-C and non-HDL-C percentiles from left to right, respectively. On the Y-axis, we represent the magnitude (%) of patient-level discordance at thresholds of ≥5, ≥10, ≥25, and ≥50 percentile units. TC/HDL-C (Total Cholesterol to HDL-C ratio); LDL-C (Low-density Lipoprotein Cholesterol); non-HDL-C (Non-High-density Lipoprotein Cholesterol).

Figure 4

Proportions with LDL-C or non-HDL-C th population percentile but discordantly high TC/HDL-C. A) The proportion of patients with LDL-C < 70 mg/dL and TC/HDL-C ≥ 2.6 (15th percentile equivalent cut-points) across various triglyceride categories B) The proportion of patients with non-HDL-C < 93 mg/dL and TC/HDL-C ≥ 2.6 (15th percentile equivalent cut-points) across various triglyceride categories. TC/HDL-C (Total Cholesterol to HDL-C ratio); LDL-C (Low-density Lipoprotein Cholesterol); non-HDL-C (Non-High-density Lipoprotein Cholesterol).

Figure 4

Proportions with LDL-C or non-HDL-C th population percentile but discordantly high TC/HDL-C. A) The proportion of patients with LDL-C < 70 mg/dL and TC/HDL-C ≥ 2.6 (15th percentile equivalent cut-points) across various triglyceride categories B) The proportion of patients with non-HDL-C < 93 mg/dL and TC/HDL-C ≥ 2.6 (15th percentile equivalent cut-points) across various triglyceride categories. TC/HDL-C (Total Cholesterol to HDL-C ratio); LDL-C (Low-density Lipoprotein Cholesterol); non-HDL-C (Non-High-density Lipoprotein Cholesterol).