Key result
Higher plasma levels of complement factors D and C3 were not independently associated with greater arterial stiffness (cfPWV) after adjusting for type 2 diabetes and metabolic risk factors.
Why the study?
Arterial stiffness predicts cardiovascular outcomes and the alternative complement pathway is implicated in cardiovascular diseases, prompting investigation into associations of factors D and C3 with arterial stiffness.
Do plasma concentrations of complement factors D and C3 associate with arterial stiffness independently of metabolic risk factors in a population-based cohort?
Cross-Sectional (n=3,019)
Do plasma concentrations of complement factors D and C3 associate with arterial stiffness independently of metabolic risk factors in a population-based cohort?
Mean Difference: 0.06 (95% CI -0.01–0.13)
p-value: p=not significant
The strong cross-sectional association between complement factors D and C3 and arterial stiffness is largely driven by metabolic risk factors such as type 2 diabetes and hypertension, rather than an independent effect.
Associations of factor D and C3 with arterial stiffness were not independent of metabolic factors; leaves open whether complement pathways contribute causally to vascular stiffness.
BACKGROUND: Arterial stiffness predicts cardiovascular outcomes. The complement system, particularly the alternative complement pathway, has been implicated in cardiovascular diseases. We herein investigated the associations of factor D, the rate-limiting protease of the alternative pathway, and C3, the central complement component, with arterial stiffness. METHODS: In 3019 population-based participants (51.9% men, 60.1 ± 8.2 years, 27.7% type 2 diabetes [T2D], oversampled]), we measured carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC) and carotid Young's elastic modulus (YEM), and plasma concentrations of factors D and C3. We conducted multiple linear regression to investigate the association of factors D and C3 (main independent variables, standardized) with cfPWV (primary outcome) and DC and YEM (secondary outcomes), adjusted for potential confounders. RESULTS: Per SD higher factors D and C3, cfPWV was 0.41 m/s [95% confidence interval: 0.34; 0.49] and 0.33 m/s [0.25; 0.41] greater, respectively. These associations were substantially attenuated when adjusted for age, sex, education, mean arterial pressure, and heart rate (0.08 m/s [0.02; 0.15] and 0.11 m/s [0.05; 0.18], respectively), and were not significant when additionally adjusted for T2D, waist circumference and additional cardiovascular risk factors (0.06 m/s [-0.01; 0.13] and 0.01 m/s [-0.06; 0.09], respectively). Results were comparable for carotid YEM and DC. In persons with T2D, but not in those without, the association between factors D and cfPWV was significant in the fully adjusted model (0.14 m/s, [0.01; 0.27], P = 0.038, Pinteraction < 0.05). CONCLUSION: The strong association of plasma factors D and C3 with arterial stiffness in this population-based cohort was not independent of T2D and other metabolic risk factors. Our data suggest that a possible causal pathway starting from alternative complement activation may via hypertension and T2D contribute to greater arterial stiffness.
No takes yet. Share an insight, caveat, or question.
Jin et al. (2022) conducted a cross-sectional in Arterial stiffness (n=3,019). Complement factors D and C3 vs. Lower concentrations (per SD) was evaluated on carotid-femoral pulse wave velocity (cfPWV) (MD 0.06 m/s (Factor D), 95% CI -0.01; 0.13, p=not significant). Higher plasma levels of complement factors D and C3 were not independently associated with greater arterial stiffness (cfPWV) after adjusting for type 2 diabetes and metabolic risk factors.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: