Physicians' Academy for Cardiovascular Education

Plaque progression more strongly associated with non-HDL-C than with LDL-C changes

Puri et al., Arterioscler Thromb Vasc Biol. 2016

Non-HDL Cholesterol and Triglycerides Implications for Coronary Atheroma Progression and Clinical Events

Puri R, Nissen SE, Shao M, et al.
Arterioscler Thromb Vasc Biol. 2016;36: published online ahead of print


Non-HDL-C encompasses all atherogenic particles containing apolipoprotein B (apoB), and predicts cardiovascular (CV) risk more accurately than LDL-C alone [1-4]. Although the International Atherosclerosis Society and the National Lipid Association consider non-HDLC to be the most important therapeutic target, non-HDL-C remains a secondary treatment goal according to European guidelines [5-7].
The association between achieved non-HDL-C and triglyceride (TG) levels and coronary atheroma progression rates have not been defined. The present analysis evaluated the relationship between achieved non-HDL-C and TG levels with the rates of plaque progression, in 4957 patients stratified according to residual metabolic risk. The residual metabolic risk was defined based on achieved LDL-C, C-reactive protein (CRP) and diabetes mellitus (DM) status. Plaque progression was assessed with coronary intravascular ultrasound (percent atheroma volume (PAV)). The effects of lower (<100 mg/dL) vs higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) vs higher (≥200 mg/dL) achieved TG levels were evaluated.

Main results

  • Lower compared with higher non-HDL-C levels and TG levels were significantly associated with greater PAV regression, irrespective of achieved LDL-C levels, CRP levels, or DM status (P<0.001 for all comparisons).
  • In a non-HDL-adjusted model, non-HDL-C was strongly associated with PAV progression: β coefficient for baseline non-HDL-C: +0.53; 95% CI: 0.41 - 0.66; P<0.001 and β coefficient for change in non-HDL-C: +0.62; 95% CI: 0.47 - 0.76; P<0.001.
  • Other predictors of PAV progression were the presence of DM (β: +0.58; 95% CI: 0.37 - 0.79; P<0.001), history of peripheral arterial disease (β: +0.49; 95% CI: 0.09 - 0.89; P=0.016), and increasing age (β: 0.02; 95% CI: 0.01 - 0.03; P<0.001).
  • Independent predictors of PAV regression included higher baseline PAV (β: −0.58; 95% CI: −0.67 to −0.49; P<0.001), female sex (β: −0.27; 95% CI: −0.46 to −0.08; P=0.005), and change in HDL-C (β: −0.14; 95% CI: −0.23 to −0.05; P=0.002).
  • In an LDL-c adjusted model, both baseline LDL-c and change in LDL-c were associated with PAV progression (β: 0.40, 95%CI: 0.26-0.53 and β:0.51, 95%CI: 0.36-0.66 respectively, both P<001). In this model, also baseline and change in TGs associated with PAV progression (β: 0.49, 95%CI: 0.29-0.70, and β: 0.48, 95%CI: 0.20-0.76, both P<0.001)
  • In this LDL-C-adjusted model, multivariable predictors of PAV changes were again the presence of DM, history of peripheral arterial disease, and increasing age.
  • At 24 months, the cumulative incidence of first MACE was significantly higher in those with: achieved non-HDLC levels ≥ median level compared with non-HDLC < median value (22.8% vs. 14.6%; log-rank P<0.001), achieved LDLC ≥ vs. <median value (22.0% vs. 15.5%; log-rank P<0.001), ≥ median vs. < median TG levels (21.2% vs. 15.9%; log-rank P<0.001) and TG ≥200 mg/dL compared with lower TG levels (23.7% vs. 17.5%; log-rank P<0.001).


Plaque progression is more strongly associated with changes in non-HDL-C than with changes in LDL-C and associates with TG levels > 200 mg/dL. Lower on-treatment non-HDL-C and TG levels were consistently associated with residual CV risk. These data support the opinion that non-HDL-C should be the primary therapeutic target for CV risk prevention.  
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1. Pischon T, Girman CJ, Sacks FM, et el. Nonhigh-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation. 2005;112:3375–3383.
2. Ridker PM, Rifai N, Cook NR, et al. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005;294:326–333.
3. Arsenault BJ, Rana JS, Stroes ES, et al. Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women. J Am Coll Cardiol. 2009;55:35–41.
4. Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302–1309.
5. Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS guidelines for the management of dyslipidaemias: The task force for the management of dyslipidaemias of the european society of cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–1818.
6. Grundy SM; Expert Dyslipidemia Panel. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia. J Clin Lipidol. 2013;7:561–565.
7. Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1–full report. J Clin Lipidol. 2015;9:129–169.