High-Density Lipoprotein Anti-Inflammatory Capacity and Incident Cardiovascular Events

Congzhuo Jia, Josephine L. C. Anderson, Eke G. Gruppen, Yu Lei, Stephan J. L. Bakker, Robin P. F. Dullaart, Uwe J. F. Tietge*

*Corresponding author for this work

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Abstract

Background:

The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. The present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population.

Methods:

HDL anti-inflammatory capacity was determined as its ability to suppress TNF alpha (tumor necrosis factor alpha)-induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression in endothelial cells in vitro (results expressed as achieved percent reduction by individual HDL related to the maximum TNF alpha effect with no HDL present). In a nested case-control design of the PREVEND (Prevention of Renal and Vascular End Stage Disease) study, 369 cases experiencing a first cardiovascular event (combined end point of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization) during a median of 10.5 years of follow-up were identified and individually matched to 369 controls with respect to age, sex, smoking status, and HDL cholesterol. Baseline samples were available in 340 cases and 340 matched controls.

Results:

HDL anti-inflammatory capacity was not correlated with HDL cholesterol or hsCRP (high-sensitivity C-reactive protein). HDL anti-inflammatory capacity was significantly lower in cases compared with controls (31.6% [15.7-44.2] versus 27.0% [7.4-36.1]; P0.05). When combining these 2 HDL function metrics in 1 model, both were significantly and independently associated with incident cardiovascular disease in a fully adjusted model (efflux: OR per 1 SD, 0.74; P=0.002; anti-inflammatory capacity: OR per 1 SD, 0.66; P

Conclusions:

The HDL anti-inflammatory capacity, reflecting vascular protection against key steps in atherogenesis, was inversely associated with incident cardiovascular events in a general population cohort, independent of HDL cholesterol and HDL cholesterol efflux capacity. Adding HDL anti-inflammatory capacity to the Framingham risk score improves risk prediction.

Original languageEnglish
Pages (from-to)1935-1945
Number of pages11
JournalCirculation
Volume143
Issue number20
Early online date12-Apr-2021
DOIs
Publication statusPublished - 18-May-2021

Keywords

  • cardiovascular diseases
  • case-control studies
  • cholesterol
  • cohort
  • inflammation
  • lipoproteins
  • HDL
  • CHOLESTEROL EFFLUX CAPACITY
  • HIGH-RISK
  • MYOCARDIAL-INFARCTION
  • DISEASE
  • INFLAMMATION
  • CREATININE
  • INHIBIT
  • PROTEIN

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