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Quantification of coronary atherosclerosis and inflammation to predict coronary events and all-cause mortality
Stefan Möhlenkamp1, Nils Lehmann, Susanne Moebus
1Clinic of Cardiology, West-German Heart Center Essen, University Clinic Duisburg-Essen, Hufelandstrasse 55, Essen, Germany. stefan.moehlenkamp@uk-essen.de
Insights
Coronary artery calcium (CAC) and high-sensitivity C-reactive protein (hsCRP) effectively predict coronary events and mortality. CAC predominantly improves risk prediction, while hsCRP is valuable for individuals with very low CAC scores.
Area of Science:
- Cardiology
- Preventive Medicine
- Biomarkers
Background:
- Coronary atherosclerosis is an inflammatory disease.
- Coronary artery calcium (CAC) measures plaque burden.
- High-sensitivity C-reactive protein (hsCRP) indicates inflammation.
Purpose of the Study:
- To assess if combined CAC and hsCRP improve prediction of coronary events and mortality.
- To evaluate the role of these biomarkers in general population risk stratification.
Main Methods:
- Measured CAC, hsCRP, and Framingham risk variables in 3,966 subjects.
- Followed subjects for 5 years to determine coronary events and all-cause mortality.
- Utilized hazard ratios, net reclassification improvement, and integrated discrimination improvement for analysis.
Main Results:
- Both CAC and hsCRP independently predicted coronary events and mortality.
- CAC significantly improved coronary risk prediction, more so than hsCRP.
- hsCRP provided additional risk information in individuals with very low CAC scores.
- A combined risk index using CAC and hsCRP thresholds showed significantly elevated risks for events and mortality.
Conclusions:
- CAC and hsCRP effectively estimate risks associated with coronary atherosclerosis and inflammation.
- CAC is the primary driver of improved coronary risk prediction.
- hsCRP plays a crucial role in refining risk assessment for individuals with minimal CAC.
Objectives:
This study sought to determine whether the evaluation of the combined presence of coronary artery calcium (CAC) and high-sensitivity C-reactive protein (hsCRP) improves discrimination and stratification of hard coronary events and all-cause mortality in the general population.
Background:
Coronary atherosclerosis is a chronic inflammatory disease. Both hsCRP as a measure of inflammation and CAC as a measure of coronary plaque burden have been shown to improve risk appraisal.
Methods:
Framingham risk variables, hsCRP, and CAC were measured in 3,966 subjects without known coronary artery disease or acute inflammation. After 5 years, incident coronary deaths, nonfatal myocardial infarction, and all-cause mortality were determined.
Results:
CAC and hsCRP independently predicted 91 coronary events (adjusted hazard ratios [HRs]: log(2)(CAC+1) = 1.25 [95% confidence interval (CI): 1.16 to 1.34], p < 0.0001; hsCRP = 1.11 [95% CI: 1.02 to 1.21], p = 0.019) and 130 deaths (adjusted HRs: log(2)(CAC+1) = 1.12 [95% CI: 1.06 to 1.19], p < 0.0001; hsCRP = 1.11 [95% CI: 1.04 to 1.19], p = 0.004). For coronary events, net reclassification improvement (NRI) was 23.8% (p = 0.0007) for CAC and 10.5% (p = 0.026) for hsCRP. Adding CAC to Framingham risk variables and hsCRP further improved discrimination of coronary risk but not vice versa. Among persons without CAC, those with hsCRP >3 mg/l versus <3 mg/l had a significantly higher coronary risk (p = 0.006). For all-cause mortality, integrated discrimination improvement (IDI) was positive when CAC or hsCRP were added to age and sex (+0.51%, p < 0.001 and +0.43%, p = 0.012, respectively). Adjusted HRs in the highest versus lowest category of a risk index derived from established CAC and hsCRP thresholds (i.e., CAC = 100 and hsCRP = 3 mg/l) were 5.92 (95% CI: 3.14 to 11.16) for coronary events and 3.02 (95% CI: 1.82 to 5.01) for all-cause mortality (p < 0.0001 each). The adjusted HR for coronary events in intermediate risk subjects was 6.98 (95% CI: 2.47 to 19.73), p < 0.001.
Conclusions:
The risk of coronary events and all-cause mortality that is mediated by the presence of coronary atherosclerosis and systemic inflammation can be estimated by CAC and hsCRP. An improvement in coronary risk prediction and discrimination was predominantly driven by CAC, whereas hsCRP appears to have a role especially in persons with very low CAC scores.
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