Divergence of Cardiovascular Biomarkers of Lipids and Subclinical Myocardial Injury Among Rheumatoid Arthritis Patients With Increased Inflammation

Arthritis Rheumatol. 2021 Jun;73(6):970-979. doi: 10.1002/art.41613. Epub 2021 May 9.

Abstract

Objective: Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury.

Methods: A total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high-sensitivity C-reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin-6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro-brain natriuretic peptide) were measured.

Results: Among the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A-I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs-cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs-cTnT levels remained stable despite a reduction in inflammation over follow-up. In both cohorts, hs-cTnT levels were associated with the overall estimated risk of CVD.

Conclusion: Among RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs-cTnT for CVD risk stratification in RA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein A-I / metabolism
  • Apolipoproteins B / metabolism
  • Arthritis, Rheumatoid / metabolism*
  • Asymptomatic Diseases
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / metabolism
  • Cholesterol / metabolism
  • Cholesterol, LDL / metabolism*
  • Female
  • Heart Disease Risk Factors
  • Heart Diseases / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Natriuretic Peptide, Brain / metabolism*
  • Peptide Fragments / metabolism*
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor, Type II / metabolism
  • Risk Assessment
  • Triglycerides / metabolism
  • Troponin T / metabolism*

Substances

  • Apolipoprotein A-I
  • Apolipoproteins B
  • Cholesterol, LDL
  • IL6 protein, human
  • Interleukin-6
  • Peptide Fragments
  • Receptors, Tumor Necrosis Factor, Type II
  • TNNT2 protein, human
  • Triglycerides
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein
  • Cholesterol