High C-reactive protein and low paraoxonase1 in diabetes as risk factors for coronary heart disease.

Atherosclerosis. 2005 Sep 1; [Epub ahead of print]  

Mackness B, Hine D, McElduff P, Mackness M.
University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. 

BACKGROUND:: Paraoxonase1 (PON1) is an anti-inflammatory enzyme located on HDL, which protects against the development of atherosclerosis. C-reactive protein (CRP) is a marker of the inflammatory response in CHD. We hypothesised that low PON1 and high CRP found in CHD may be important markers of CHD and the CRP:PON1 ratio may be an index of the risk of developing atherosclerosis. We have, therefore, compared the levels of PON1 and CRP between control subjects, those with no diabetes and CHD, type 1 diabetes and type 2 diabetes.

METHODS AND RESULTS:: PON1 activity was different between the populations in the order: controls>type 1 diabetes>type 2 diabetes>CHD with no diabetes (P<0.001). CRP concentration also differed between the populations in the order: controls<type 1 diabetes<type 2 diabetes<CHD with no diabetes (P<0.001). The CRP:PON1 ratio followed the same trend as the CRP concentration (P<0.001). Both CRP and the CRP:PON1 ratio were associated with the presence of CHD. In the control population only, PON1 was a determinant of CRP concentration. Amongst the diabetics, people with CHD had higher levels of CRP (P<0.001) and in comparing the control group with the CHD group, the CHD group had a higher level of CRP (P<0.001).

CONCLUSIONS:: Higher levels of CRP seem to be generally associated with low levels of PON1 activity, providing a mechanistic link between inflammation and the development of atherosclerosis. However, the relationship between PON1, CRP and atherosclerosis, and the usefulness of the PON1:CRP ratio as a risk factor for CHD requires further evaluation.