Ridker · Circulation 2004 · prospective cohort study · n=27939

Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores.

Cited 514 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective cohort study of cardiovascular outcomes.

PubMed 15051634 · doi:10.1161/01.CIR.0000125690.80303.A8 · record verified 2026-08-28

What was done

Baseline levels of high-sensitivity C-reactive protein (hsCRP) were assessed in 27,939 apparently healthy women followed prospectively for incident cardiovascular events (myocardial infarction, stroke, coronary revascularization, or cardiovascular death). Crude and Framingham Risk Score (FRS)-adjusted relative risks (RRs) were computed across nine strata of hsCRP (<0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <3.0, 3.0 to <4.0, 4.0 to <5.0, 5.0 to <10.0, 10.0 to <20.0, and ≥20.0 mg/L), with additional stratification by FRS and adjustment for diabetes.

What was found

In the cohort, 15.1% of women had hsCRP <0.50 mg/L and 5.4% had hsCRP >10.0 mg/L. Cardiovascular risk increased linearly with hsCRP. Crude RRs across the nine ascending tiers were 1.0 (referent), 2.2, 2.5, 3.1, 3.7, 4.2, 4.9, 6.3, and 7.6 (P for trend <0.001). After adjustment for FRS, the RRs were 1.0, 1.6, 1.6, 1.7, 1.9, 2.2, 2.3, 2.8, and 3.1 (P for trend <0.001). All risk estimates remained statistically significant after stratifying by FRS and controlling for diabetes.

Why it matters

This study demonstrates that the prognostic value of hsCRP extends beyond standard clinical cutpoints (1 to 3 mg/L), showing that very low (<0.5 mg/L) and very high (>10 mg/L) levels continue to stratify cardiovascular risk across all FRS categories.

Limits

The study included only apparently healthy women, limiting direct generalizability to men or individuals with pre-existing cardiovascular conditions. The abstract does not report the duration of follow-up, total event counts, or confidence intervals around the relative risk estimates.

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