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Serum complement C3/C4 ratio, a novel marker for recurrent cardiovascular events
Anil Palikhe1, Juha Sinisalo, Mikko Seppänen
1Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Insights
The study found that a higher serum complement C3 and C4 concentration ratio (C3/C4 ratio) predicts recurrent cardiovascular events in acute coronary syndrome patients. This ratio serves as a novel, accessible marker for cardiovascular risk assessment.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Acute coronary syndrome (ACS) is characterized by inflammation and complement cascade activation.
- The role of complement system components in predicting cardiovascular events in ACS patients requires further investigation.
Purpose of the Study:
- To evaluate the serum complement C3 and C4 concentration ratio (C3/C4 ratio) as a predictive marker for subsequent ischemic cardiovascular events in patients with ACS.
- To determine if the C3/C4 ratio is an independent risk factor for recurrent cardiovascular events after an initial ACS episode.
Main Methods:
- A cohort of 148 ACS patients was followed for a median of 555 days for major adverse cardiovascular events.
- Serum samples were collected at multiple time points: hospitalization, 1 week, 3 months, and 1 year post-admission.
- Serum C3 and C4 concentrations were measured, and the C3/C4 ratio was calculated and analyzed using statistical models, including Cox regression.
Main Results:
- Patients who experienced subsequent cardiovascular events had a significantly higher C3/C4 ratio throughout the follow-up period compared to those who did not (p=0.007).
- The C3/C4 ratio was identified as a novel independent risk factor for new cardiovascular events (OR 1.33, p=0.007).
- Patients in the highest quartile of the C3/C4 ratio had a 3.04-fold increased risk of experiencing an event compared to those in the lowest quartiles (p=0.01).
Conclusions:
- An elevated serum C3/C4 ratio is a novel and readily available marker for predicting recurrent cardiovascular events in patients with acute coronary syndrome.
- The findings suggest that changes in complement C3 and C4 protein levels contribute to cardiovascular risk stratification in ACS.
- The C3/C4 ratio offers a potential tool for enhanced risk assessment and management strategies in ACS patients.
Abstract:
Acute coronary syndrome is an inflammatory disease, during which the complement cascade is activated. We assessed the complement C3 and C4 concentration ratio (C3/C4 ratio) in serum as a potential measurement to predict cardiovascular attacks. Patients with acute coronary syndrome (n=148) were followed after an initial attack for subsequent ischemic cardiovascular events (composite end point of death, myocardial infarction, recurrent unstable angina, or stroke). During the follow-up period (average 555 days), 44 patients met an end point. Blood samples were taken at hospitalization, 1 week, 3 months, and 1 year after hospital admission. Serum complement C3 and C4 concentrations and the C3/C4 ratio were analyzed. Patients with an end point had, throughout the follow-up period, a higher C3/C4 ratio than patients without these end points (repeated measures analysis of variance, p=0.007). When all traditional cardiovascular risk factors and other potential confounding factors were included in a Cox multivariate logistic regression survival analysis, the C3/C4 ratio emerged as the novel risk factor for any new cardiovascular event (odds ratio 1.33, 95% confidence interval 1.08 to 1.63, p=0.007). When the C3/C4 ratio was divided into 4 quartiles, 24% in quartiles 1 and 2 (lowest) and 48% in quartile 4 (highest) had end points during follow-up (odds ratio 3.04, 95% confidence interval 1.27 to 7.29, p=0.01). In conclusion, increased serum C3/C4 ratio is a readily available and novel marker for recurrent cardiovascular events in acute coronary syndrome. The relative increase in serum C3 protein and decrease in C4 protein could explain changes in the C3/C4 ratio.
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