Low-density lipoprotein (LDL) cholesterol is an established risk factor for cardiovascular disease; however, a substantial portion of atherothrombotic events occur in patients who are without hyperlipidemia. Several studies have shown that the C-reactive protein level is associated with an increased risk of cardiovascular events. Ridker and colleagues present corroborating evidence from a population-based study of women that examined the association between C-reactive protein and LDL cholesterol levels and cardiovascular disease.

The researchers used data from the Women’s Health Study to evaluate values for C-reactive protein and LDL cholesterol in 27,939 women. The average age of study participants was 54.7 years, and 44 percent were current users of hormone replacement therapy. Subjects were followed for a mean of eight years for the first occurrence of a cardiovascular event (myocardial infarction, ischemic stroke, coronary revascularization, or death).

There was a strong linear correlation between cardiovascular events and increased C-reactive protein and LDL cholesterol levels. When C-reactive protein values were divided into quintiles of increasing levels, the relative risks of sustaining a first cardiovascular event increased in a stepwise fashion. After adjustment for age, smoking status, diabetes, blood pressure, and the use of hormone replacement therapy, the relative risk was set at 1.0 for the lowest quintile of C-reactive protein (less than 0.49 mg per L). The relative risk of cardiovascular disease increased with each quintile to 1.4, 1.6, 2.0, and, finally, 2.3 for the highest quintile of C-reactive protein (greater than 4.19 mg per L). Various statistical methods (such as chi-square) verified that C-reactive protein level was a better discriminator of cardiovascular risk than LDL cholesterol level. Of the cardiovascular events recorded among women in the study, 46 percent occurred in those with LDL levels less than 130 mg per dL (3.36 mmol per L).

The study also showed very little correlation between C-reactive protein and LDL levels, suggesting that each of these parameters identified an independent risk for cardiovascular disease. A combination of low C-reactive protein and low LDL level conferred the best probability of event-free survival, while high C-reactive protein combined with high LDL level had the greatest associated cardiovascular risk (see accompanying figure).

The authors concluded that increasing levels of C-reactive protein are an independent predictor of cardiovascular events and are even more strongly associated with cardiovascular risk than increased LDL cholesterol levels.