TY - JOUR
T1 - Soluble CD40 ligand expression in stable atherosclerosis
T2 - A systematic review and meta-analysis
AU - Pereira-da-Silva, Tiago
AU - Ferreira, Vera
AU - Castelo, Alexandra
AU - Caldeira, Daniel
AU - Napoleão, Patrícia
AU - Pinheiro, Teresa
AU - Ferreira, Rui Cruz
AU - Carmo, Miguel Mota
PY - 2021/2
Y1 - 2021/2
N2 - Background and aims: The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation and atherogenesis. Through a systematic review and meta-analysis, we assessed whether sCD40L was dysregulated in stable atherosclerosis, irrespective of the diseased arterial territory, and whether this dysregulation differed according to the specific territory. Methods: Systematic literature searches were performed in MEDLINE, Cochrane Library, Web of Science, and Embase for studies reporting circulating sCD40L levels in individuals with and without stable atherosclerosis. sCD40L levels were compared using random-effects meta-analysis, weighted by the inverse variance method (study protocol: PROSPERO CRD42020181392). Results: Fifty-four studies (59 estimates) including 7705 patients and 7841 controls were analyzed. sCD40L levels were found to be increased in patients with atherosclerosis, irrespective of the territory (standardized mean difference [SMD] 0.43, 95% CI 0.29–0.57; 59 estimates; χ2 heterogeneity p < 0.001; I2 = 92%). SMD was greatest in carotid atherosclerosis (SMD 0.58, 95% CI 0.30–0.86; 17 estimates), followed by coronary (SMD 0.43, 95% CI 0.24–0.62; 33 estimates), lower extremity (SMD 0.26, 95% CI -0.02–0.54; 7 estimates), and renal atherosclerosis (SMD -0.07, 95% CI -2.77–2.64; 2 estimates) (χ2 heterogeneity p < 0.001; I2 ≥ 80% for all). Subgroup analysis revealed that sCD40L levels were increased in clinical, but not subclinical, atherosclerosis. Conclusions: sCD40L levels were increased in stable atherosclerosis, particularly in the carotid and coronary territories. These novel data support sCD40L as a marker of systemic atherosclerosis, possibly with differential roles in specific territories.
AB - Background and aims: The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation and atherogenesis. Through a systematic review and meta-analysis, we assessed whether sCD40L was dysregulated in stable atherosclerosis, irrespective of the diseased arterial territory, and whether this dysregulation differed according to the specific territory. Methods: Systematic literature searches were performed in MEDLINE, Cochrane Library, Web of Science, and Embase for studies reporting circulating sCD40L levels in individuals with and without stable atherosclerosis. sCD40L levels were compared using random-effects meta-analysis, weighted by the inverse variance method (study protocol: PROSPERO CRD42020181392). Results: Fifty-four studies (59 estimates) including 7705 patients and 7841 controls were analyzed. sCD40L levels were found to be increased in patients with atherosclerosis, irrespective of the territory (standardized mean difference [SMD] 0.43, 95% CI 0.29–0.57; 59 estimates; χ2 heterogeneity p < 0.001; I2 = 92%). SMD was greatest in carotid atherosclerosis (SMD 0.58, 95% CI 0.30–0.86; 17 estimates), followed by coronary (SMD 0.43, 95% CI 0.24–0.62; 33 estimates), lower extremity (SMD 0.26, 95% CI -0.02–0.54; 7 estimates), and renal atherosclerosis (SMD -0.07, 95% CI -2.77–2.64; 2 estimates) (χ2 heterogeneity p < 0.001; I2 ≥ 80% for all). Subgroup analysis revealed that sCD40L levels were increased in clinical, but not subclinical, atherosclerosis. Conclusions: sCD40L levels were increased in stable atherosclerosis, particularly in the carotid and coronary territories. These novel data support sCD40L as a marker of systemic atherosclerosis, possibly with differential roles in specific territories.
KW - Atherosclerosis
KW - Carotid artery disease
KW - Coronary artery disease
KW - Inflammation
KW - Lower extremity arterial disease
KW - Renal artery disease
KW - Soluble CD40 ligand
UR - http://www.scopus.com/inward/record.url?scp=85099660401&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2020.12.011
DO - 10.1016/j.atherosclerosis.2020.12.011
M3 - Article
C2 - 33494009
AN - SCOPUS:85099660401
SN - 0021-9150
VL - 319
SP - 86
EP - 100
JO - Atherosclerosis
JF - Atherosclerosis
ER -