High-sensitivity CRP may be a marker of HDL dysfunction and remodeling in patients with acute coronary syndrome

Abstract

In patients with coronary artery disease (CAD), further increasing the level of high-density lipoprotein (HDL) cholesterol (HDL-C) as an add-on to statins cannot reduce cardiovascular risk. And it has been reported that HDL functional metric—cholesterol efflux capacity (CEC) may be a better predictor of CAD risk than HDL-C. CEC measurement is time-consuming and not applicable in clinical settings. Thus, it is meaningful to explore an easily acquired index for evaluating CEC. Thirty-six CAD patients and sixty-one non-CAD controls were enrolled in this cross-sectional study. All CAD patients had acute coronary syndrome (ACS). CEC was measured using a [3H] cholesterol loading Raw 264.7 cell model with apolipoprotein B-depleted plasma (a surrogate for HDL). Proton nuclear magnetic resonance (NMR) spectroscopy was used to assess HDL components and subclass distribution. CEC was significantly impaired in CAD patients (11.9 ± 2.3%) compared to controls (13.0 ± 2.2%, p = 0.022). In control group, CEC was positively correlated with enzymatically measured HDL-C levels (r = 0.358, p = 0.006) or with NMR-determined HDL-C levels (NMR-HDL-C, r = 0.416, p = 0.001). However, in CAD group, there was no significant correlation between CEC and HDL-C (r = 0.216, p = 0.206) or NMR-HDL-C (r = 0.065, p = 0.708). Instead, we found that the level of high-sensitivity C-reactive protein (hsCRP) was inversely associated with CEC (r = − 0.351, p = 0.036). Multiple regression analysis showed that the hsCRP level was associated with CEC after adjusting other cardiovascular risk factors and HDL-C, although the association would not reach significance if adjusting for multiple testing. NMR spectroscopy showed that HDL particles shifted to larger ones in patients with high hsCRP levels, and this phenomenon was accompanied by decreased CEC. In patients with CAD, the level of HDL-C cannot reflect HDL function. The impaired correlation between HDL-C and CEC is possibly due to an inflammation-induced HDL subclass remodeling. These hypothesis-generating data suggest that hsCRP levels, a marker of acute inflammation, may associate with HDL dysfunction in ACS subjects. Due to the design limited to be correlative in nature, not permitting causal inference and a larger, strictly designed study is still needed.

Inflammation in coronary artery disease-clinical implications of novel HDL-cholesterol–related inflammatory parameters as predictors

“…Notably, elevated hs-CRP with low HDL-C level is significantly linked to an increased incidence of all-cause death in patients who received PCI. Moreover, hs-CRP is found to be inversely associated with the RCT of HDL and the association between hs-CRP and coronary artery calcification score could be modified by HDL-C [ 7 , 104 ]. Therefore, hs-CRP to HDL-C ratio (CHR) is explored and has been discovered to be an independent predictor of CAD presence (adjusted OR, 1.178; 95% CI, 1.016–1.366; P = 0.03) with a specificity of 86.7%, Yoden index of 0.264 and AUC of 0.662 (95% CI, 0.606–0.719; P < 0.001) [ 91 ].…”

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS

“…Some studies have suggested, based on the observation that individuals with higher levels of large HDL particles have a lower risk of CVD, that larger HDL particles are more protective against CVD than smaller HDL particles [ 28 , 29 ]. On the contrary, other studies showed that small, dense HDL particles may actually be more protective against CVD than larger particles [ 30 , 31 , 32 ]. This controversy suggests that the relationship between HDL particle size and CVD risk is complex and may depend on other factors such as the presence of other lipid abnormalities or genetic factors [ 33 ].…”

Anti-hyperglycemic, anti-hyperlipidemic, and anti-inflammatory effect of the drug Guggulutiktaka ghrita on high-fat diet-induced obese rats

“…According to a study, HDL cholesterol levels might not be a good predictor of MACE in CAD patients, i.e., serum levels of HDL cholesterol might not accurately reflect the true cholesterol efflux capacity of HDL. The researchers further found that the assessment of cholesterol efflux capacity provided the most reliable reflection of HDL function and cardiovascular risk and speculated that the disjunction between serum HDL concentration and its functional capacity might be caused by inflammation-induced remodeling of HDL subclass [ 34 ]. In another study, the cholesterol efflux capacity was reduced in ACS patients and remained low during the 3-month follow-up period when compared to stable CAD patients, independent of changes in HDL cholesterol levels or Apo lipoprotein A-I.…”