C-Reactive Protein, the Metabolic Syndrome, and Risk of Incident Cardiovascular Events - C-Reactive Protein, the Metabolic Syndrome, and Risk of Incident Cardiovascular Events


The goal of this study was to evaluate the interrelationships between CRP, the metabolic syndrome, and cardiovascular events


To determine whether elevated CRP levels added prognostic information on risk of subsequent cardiovascular events across the individual component of the metabolic syndrome.

Study Design

Study Design:

Patients Screened: 28,345
Patients Enrolled: 14,719
Mean Follow Up: 8 years
Mean Patient Age: mean age 54 years
Female: 100

Patient Populations:

Enrolled in the Women’s Health Study; American women age >=45 years with no prior history of cardiovascular disease or cancer


Diabetes at study entry; use of horomone replacement therapy at study entry

Primary Endpoints:

Incident cardiovascular events, including nonfatal MI, nonfatal ischemic stroke, coronary revascularization procedures, and cardiovascular death.

Drug/Procedures Used:

Baseline CRP levels were measure. Women with >=3 of the following attributes were defined as having metabolic syndrome: (1) triglycerides >=150 mg/dL; (2) HDL cholesterol <50 mg/dL; (3) blood pressure >=135/85 mm Hg; (4) obesity as defined as BMI >26.7 kg/m2; and (5) diagnosis of incident type II diabetes during study follow-up.

Principal Findings:

Three or more of the metabolic attributes were present in 24.4% of patients at baseline. CRP levels were significantly higher among patients who had each of the individual component of the metabolic syndrome than among women who did not (p<0.0001 for each). The CRP levels increased with an increase in the number of components of the metabolic syndrome (CRP 0.68, 1.09, 1.93, 3.01, 3.88, and 5.75 mg/L, for 0, 1, 2, 3, 4, and 5 metabolic characteristics, respectively (p<0.0001 for trend). Cardiovascular events were higher in patients with CRP >3.0 mg/L vs CRP <=3.0 in patients with 3, 4, or 5 components of metabolic syndrome (p<0.001 for each). The predictive values for the development of first cardiovascular events was similar using CRP levels above or below 3.0 mg/L or >=3 or <3 metabolic syndrome components (ROC 0.77 for CRP vs 0.78 for metabolic syndrome. In analysis of the 3597 patients with >=3 metabolic syndrome characteristics at baseline, rates of cardiovascular events were higher with higher levels of baseline CRP (3.4 vs 5.9 events per 1000 person-years of exposure for CRP <=3.0 or >3.0 mg/L, respectively p<0.001). When grouped by presence or absence of both CRP elevation and metabolic syndrome, the age-adjusted relative risks of future cardiovascular events for women in the low-CRP/no metabolic syndrome, high-CRP/no metabolic syndrome, low-CRP/yes metabolic syndrome, and high-CRP/yes metabolic syndrome groups were 1.0, 1.5 (95% CI 1.0 to 2.2), 2.3 (95% CI 1.6 to 3.3), and 4.0 (95% CI 3.0 to 5.4), respectively.


This study demonstrates that the presence of >=3 components of the metabolic syndrome was associated with an increased risk of cardiovascular events in healthy women. In addition, the study showed that CRP provided additional prognostic and risk stratification information in addition to metabolic syndrome for future cardiovascular events in healthy women. Use of CRP for risk stratification and the targeted use of primary prevention treatments may be warrented given these findings. Due to the nature of the study, only women were included. However, the authors note that extrapolation of the results to men is reasonable since CRP has been shown to predict events in men in other trials.


Circulation. 2003;107:391-397.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins

Keywords: Metabolic Syndrome X, Risk, Coronary Artery Disease, Neoplasms, Body Mass Index, Diabetes Mellitus, Type 2, Blood Pressure, Cholesterol, HDL, Obesity, Triglycerides, Primary Prevention, United States

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