In order to investigate the relationship between plasma high-sensitivity C-reactive protein levels (CRP) and risk of coronary heart disease (CHD) in a Japanese population, investigators of the Hisayama study prospectively studied 2,589 men and women over 40 years of age for 14 years. During follow-up, 129 CHD cases were reported. CHD was defined as myocardial infarction, coronary revascularization, or sudden cardiac death. Participants in the top CRP quartile had an age and sex-adjusted odds ratio (OR) of future CHD of 3.96 (95% CI, 2.07-7.57) and of 2.98 (95% CI, 1.53-5.82) upon further adjustment for systolic blood pressure, ECG abnormalities, diabetes, body mass index, total and HDL cholesterol levels, smoking, alcohol intake, and physical activity. CHD risk associated with elevated CRP levels appeared to be higher in participants with hypertension or hypercholesterolemia and in smoking individuals. CRP did not predict CHD risk in obese and/or diabetic participants. Based on their observations, the authors suggested that 1.0 mg/l could represent a cut-off point for identifying Japanese with elevated plasma CRP levels, a cut-off point that is lower compared to that for Caucasians. The paper was accompanied by an editorial by Paul M. Ridker who reviewed the latest studies that have provided evidence for CRP’s role in the pathophysiology of CHD or CHD risk prediction. In his opinion, the Hisayama study provided further evidence for a graded and constant relationship between plasma CRP levels and CHD risk, similar to what has been reported in the Women’s Health Study. Clinical and epidemiological studies have reported that even at low LDL cholesterol levels, a residual risk appears to be associated with elevated CRP levels. Based on this observation, Ridker expressed his belief that the time has come for the field to move towards clinical trials aimed at lowering inflammation or plasma CRP levels in particular.
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