Epidemiological studies have shown an association between moderately elevated CRP levels and incident CHD whereas genetic studies have shown that polymorphisms associated with elevated CRP levels do not increase the risk of ischemic vascular disease, suggesting that CRP might be a bystander rather than a causal factor in the progress of atherosclerosis.
This association may be causal (either directly or indirectly) or simply a confounder resulting from the recognized relationship between CRP and vascular disease.
The importance of the relationship of CRP gene variants to CRP serum level and cardiovascular disease risk is important to establish CRP gene profiling as a clinical risk prediction tool and also to help test the cause-effect relationship between CRP and vascular disease.
Polymorphisms in the CRP gene are associated with marked increases in CRP levels and thus with a theoretically predicted increase in the risk of ischemic vascular disease.
Thus, common variation in several genes involved in metabolic and inflammatory regulation have significant effects on CRP levels, consistent with CRP's identification as a useful biomarker of risk for incident vascular disease and diabetes.
Both APOE e4 allele (APOE4) and C-reactive protein (CRP) are associated with greater risk of dementia and vascular disease, but APOE4 carriers have lower blood concentrations of CRP than do noncarriers, possibly through a mechanism favoring the clearance of the CRP VLDL-bound fraction.
As CRP is so strongly associated with vascular disease it has been suggested that this hepatic-derived protein is not only a marker, but also a mediator of vascular disease.
Accumulating evidence suggests that C-reactive protein (CRP), in addition to predicting vascular disease, may actively facilitate lesion formation by inciting endothelial cell activation.