Human plasma complement C3 is independently associated with coronary heart disease, but only in heavy smokers (the CODAM study)

Greevenbroek, Marleen M.J. van; Jacobs, Madelon; Kallen, Carla; Blaak, Ellen E.; Jansen, Eugène; Schalkwijk, Casper G.; Feskens, Edith J. M.; Stehouwer, Coen D. A.

doi:10.1016/j.ijcard.2010.09.017

Cited by 28 publications

(26 citation statements)

References 37 publications

(44 reference statements)

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“…To the best of our knowledge, this is the first time that such an association has been reported in HD patients despite many reports of a similar positive association in non-dialysis populations [1,2,3,4,5,6,7,8,9]. The high incidence of CV disease in HD patients [16,21] and the ability of HD to activate the complement system [11,12,13,14] are both well established.…”

Section: Discussionmentioning

confidence: 82%

“…A number of observational series in non-renal populations have reported positive associations between the circulating levels of components of the complement system, such as C3 and the terminal complement complex SC5b-9, and both prevalent [1,2,3,4,5] and incident [6,7,8,9,10] cardiovascular (CV) disease. Enhanced complement activation, particularly via the alternative complement activation pathway, occurs in haemodialysis (HD) patients largely as a consequence of blood-membrane interactions and is partially attenuated by the use of newer, biocompatible membranes [11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

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Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Lines

Richardson²,

Thomas

et al. 2015

Nephron

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Background: Patients on haemodialysis (HD) have high rates of cardiovascular (CV) disease and activation of the complement system. Despite evidence in non-renal patients that these may be linked, this association has received little attention in HD patients to date. In the setting of a randomised controlled trial we evaluated the relationships between baseline complement levels and subsequent CV events and mortality, in addition to the effects of HD with a vitamin E (VE)-coated dialysis membrane on circulating complement levels. Methods: A total of 260 HD patients were randomised to dialysis with a VE-coated dialysis membrane or non-VE coated equivalent for 12 months. Blood samples were taken at baseline, 6 and 12 months for measurement of C3, factor D, factor H and SC5b-9 levels. Data were collected prospectively on deaths and CV events. Results: Higher C3 levels at baseline were associated with subsequent CV events (hazard ratio 1.20 (1.01-1.42) per 0.1 mg/ml). Patients with intermediate SC5b-9 levels had significantly lower CV event rates and mortality than those with either high or low levels (p < 0.01). There were no effects of the VE-membranes on the complement components measured nor the clinical endpoints considered. Conclusions: The levels of C3 and SC5b-9 may have prognostic utility for predicting future CV events and/or mortality in HD patients - a relationship that requires further investigation. Dialysing prevalent HD patients with VE-bonded polysulfone membranes for a period of 12 months did not alter the circulating levels of the alternative complement pathway components considered here.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Lines

Richardson²,

Thomas

et al. 2015

Nephron

View full text Add to dashboard Cite

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“…Individuals with antitoxin level >5.0 IU/ml should be controlled after 8 years. Similar guideline has been presented for re-vaccination by Centers for Disease Control and Prevention [36,37]. The CDC's Advisory Committee on Immunization Practices recommended that all smokers aged 19-64 years be vaccinated with the pneumococcal polysaccharide vaccine [38,39].…”

Section: Figure 1: Distribution Of Subjects According To Anti-tetanusmentioning

confidence: 99%

Lower immunity to tetanus in cigarette smoker subjects

Jafarzadeh

Shabani

Hassanabadi

et al. 2012

JOHE

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Received: February 2013, Accepted: October 2013 Background: Cigarette smoking has been linked with the suppression of immune responses and increased susceptibility to numerous infections in humans. Tetanus is also a major public health problem in many countries. The aim of the present study was to evaluate the serum levels of antitetanus toxin antibodies in cigarette smoking and healthy non-smoking people. Materials and Methods: A total of 100 cigarette smokers and 100 age-matched healthy nonsmoker individuals were enrolled in this descriptive study. A blood sample was collected from each participant. The samples were tested for the levels of anti-tetanus toxin antibodies by use of enzyme linked immunosorbent assay. Results: The seroprotective rate of anti-tetanus toxin antibodies in non-smoking group (99%) was significantly higher than that observed in cigarette smoking group (78%, P<0.0001). The mean titer of anti-tetanus toxin antibodies in non-smoking group (5.32± 0.26 IU/ml) was also significantly higher than that in smoker subjects (1.03 ± 0.16 IU/ml; P<0.0001). The mean titer of anti-tetanus toxin antibodies in individuals with smoking duration >10 years was significantly lower than that among smokers with smoking duration ≤10 years (0.59 ± 0.12 IU/ml vs 1.98 ± 0.41 IU/ml; P<0.001). The seroprotection rate was also significantly lower in persons with smoking duration >10 years in comparison to smokers with smoking duration ≤10 years (72.1% vs 90.6%; P=0.037). The mean titer of anti-tetanus toxin antibodies in individuals with daily smoking >10 cigarettes was also significantly lower in comparison to smokers with daily smoking ≤10 cigarettes (0.68 ± 0.15 IU/ml vs 1.63 ± 0.36 IU/ml; P<0.001). Conclusion: These results showed lower levels of anti-tetanus toxin antibodies in cigarette smokers which represents cigarette smoking as a risk factor for susceptibility to tetanus. A negative association was also observed between the immunity to tetanus and smoking burden.

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“…In recent years, there have been an increasing number of studies focusing on complement and innate immune system proteins in relation to obesity, inflammation, and dyslipidemias [2], [3], [4]. Studies in humans have demonstrated that C3, the most abundant component of the complement cascade, and its mediator molecules are increased in obesity, metabolic syndrome and cardiovascular disease [2], [5], [6], [7], [8], [9], [10]. However, in spite of the strong associations of C3 with obesity and metabolic syndrome, the underlying mechanisms remain unexplained.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Complement C3 and C3aR Expression in Subcutaneous Adipose Tissue in Obese Women

et al. 2014

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BackgroundThe central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.MethodsWomen (n = 140, 21–69 years, BMI 19.5–79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.ResultsSubjects were separated into groups (n = 34–36) according to obesity: normal/overweight (≤30 kg/m2), obese I (≤45 kg/m2), obese II (≤51 kg/m2), and obese III (≤80 kg/m2). Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05–0.0001). While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05). Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and C3aR expression (p<0.05–0.001) or less).ConclusionsThe obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.

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Human plasma complement C3 is independently associated with coronary heart disease, but only in heavy smokers (the CODAM study)

Cited by 28 publications

References 37 publications

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Lower immunity to tetanus in cigarette smoker subjects

Downregulation of Complement C3 and C3aR Expression in Subcutaneous Adipose Tissue in Obese Women

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