The association between the metabolic syndrome and peripheral, but not coronary, artery disease is partly mediated by
Marjon Jacobs1, Marleen M J van Greevenbroek, Carla J H van der Kallen
1Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands. marjon.jacobs@intmed.unimaas.nl
Insights
Metabolic syndrome is linked to peripheral artery disease (PAD) severity through endothelial dysfunction, but not coronary artery disease (CAD). This suggests distinct underlying mechanisms for these cardiovascular conditions.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Vascular Biology
Background:
- Metabolic syndrome is associated with coronary artery disease (CAD) and peripheral artery disease (PAD).
- The precise mechanisms linking metabolic syndrome to CAD and PAD severity remain unclear.
- Investigating the role of endothelial dysfunction and inflammation in these associations is crucial.
Purpose of the Study:
- To determine if endothelial dysfunction mediates the association between metabolic syndrome and CAD.
- To assess if endothelial dysfunction mediates the association between metabolic syndrome and PAD severity (measured by ankle-arm index, AAIx).
- To evaluate if these mediating roles are independent of low-grade inflammation.
Main Methods:
- Studied 539 at-risk subjects (mean age 59.4 years).
- Assessed endothelial dysfunction and inflammation using validated biomarker scores.
- Employed logistic and linear regression analyses, adjusted for age, sex, and smoking.
Main Results:
- Metabolic syndrome was associated with higher CAD prevalence (OR 1.75) and lower AAIx (β -0.036).
- Endothelial dysfunction explained 6% of the metabolic syndrome-CAD association and 19% of the metabolic syndrome-PAD association.
- Low-grade inflammation explained 26% and 28% of these associations, respectively. Combined, they explained 24% (CAD) and 36% (PAD).
Conclusions:
- Endothelial dysfunction partially mediates the link between metabolic syndrome and PAD severity.
- Endothelial dysfunction does not appear to mediate the association between metabolic syndrome and CAD.
- These findings suggest distinct pathophysiological pathways for coronary and peripheral artery diseases in the context of metabolic syndrome.
Background:
The metabolic syndrome is associated with coronary artery disease (CAD) and with peripheral artery disease (PAD), but the underlying mechanisms explaining these associations have not yet been completely clarified. The aim was to investigate (i) whether endothelial dysfunction can explain the association between the metabolic syndrome and CAD and/or the severity of PAD, as measured by the ankle-arm index (AAIx); and (ii) whether any such mediation is independent of that from low-grade inflammation.
Materials And Methods:
We studied 539 subjects (232 men) aged 59·4 ± 6·9 years, with an increased risk of type 2 diabetes and cardiovascular diseases. Endothelial dysfunction and inflammation scores were calculated from three markers of endothelial dysfunction (soluble E-selectin, soluble vascular cell adhesion molecule-1 and von Willebrand factor) and six of inflammation (C-reactive protein, interleukin 6, soluble intercellular adhesion molecule-1, serum amyloid A, ceruloplasmin and haptoglobin). The association between the metabolic syndrome and CAD and/or PAD, and the mediating role of endothelial dysfunction herein was examined with logistic and linear regression analyses, all adjusted for age, sex and smoking.
Results:
Subjects with the metabolic syndrome (n = 289; 54%) had higher prevalence of CAD [OR (95%CI) = 1·75 (1·14; 2·69)] and lower AAIx [β (95% CI) = -0·036 (-0·056; -0·016)]. Endothelial dysfunction explained 6% of the association between the metabolic syndrome and CAD, and 19% of the association with AAIx, whereas low-grade inflammation explained 26% and 28% of these associations, respectively. Together, the two scores explained 24% and 36% of the association between the metabolic syndrome and CAD and AAIx, respectively.
Conclusions:
Endothelial dysfunction explains part of the association between the metabolic syndrome and the severity of PAD, but is not involved in the association between the metabolic syndrome and CAD. This indicates that the pathophysiologies of coronary and peripheral artery disease are essentially distinct.
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