Questions: What is the relationship between C-reactive protein (CRP), the metabolic syndrome, and incident cardiovascular events? Does CRP add prognostic information to cardiovascular risk prediction among people with varying components of the metabolic syndrome? Population: American women aged 45 years or older with no prior history of cardiovascular disease or cancer included in the Women’s Health Study (WHS) (a primary prevention trial studying aspirin and vitamin E). Women on hormone replacement therapy or who had a diagnosis of diabetes were excluded. Design and methods: In a prospective cohort study with an eight-year follow-up period, 14 719 women were followed. Baseline frozen blood samples were thawed and assayed for CRP, triglycerides and HDL-cholesterol levels. The Adult Treatment Panel (ATP) III criteria for the metabolic syndrome were modifi ed by the investigators due to the lack of fasting glucose and waist circumference measurements at baseline. The criteria for the metabolic syndrome used in this analysis were three or more of the following components: (1) triglycerides $150 mg/dl (1.7 mmol/l), (2) HDL-cholesterol,50 mg/dl (1.29 mmol/l), (3) blood pressure .135/85 mmHg, (4) obesity as defi ned by a body mass index (BMI) .26.7 kg/m2 was used as an approximation for a waist circumference of .88 cm (a BMI of 26.7 kg/m2 correlated to the same percentile of BMI as did a waist circumference of 88 cm measured at year 6), and (5) diagnosis of incident type 2 diabetes during study follow-up (as an approximation for a fasting glucose $110 mg/dl (6.11 mmol/l)). Study subjects were classifi ed as having 0, 1, 2, 3, 4 or 5 components of the metabolic syndrome and median CRP levels within each of these groups were determined. The primary outcomes of interest were myocardial infarction, stroke, coronary revascularization or cardiovascular (CV) death, and logistic regression analysis was used to determine if a CRP level .3 mg/l was an independent predictor of CV events over and above metabolic syndrome factors. This CRP cutpoint of 3 mg/l was used to distinguish high- and low-risk groups based on the recommendations of the Centers for Disease Control and Prevention. Eight-year cardiovascular event-free survival curves were constructed comparing cohorts with CRP levels above and below 3 mg/l and comparing those women with and without three or more components of the metabolic syndrome. Results: Loss to follow-up was not reported. The prevalence of the metabolic syndrome was 24.4% (95% confi dence interval (CI) 23.6-25.2). CRP levels increased progressively among women with an increasing number of metabolic syndrome components, compared with women who did not have any features of the metabolic syndrome. The median CRP increased from 0.68 to 1.09, 1.93, 3.01, 3.88 and 5.75 mg/l for those with 0, 1, 2, 3, 4 and 5 components of the metabolic syndrome, respectively (p for trend,0.0001). With increasing criteria of the metabolic syndrome, CRP was an independent predictor of future CV events. Among women with the metabolic syndrome, the age-adjusted incidence rates of CV events were 3.4 and 5.9 events per 1000 person-years for those with baseline CRP levels less than or greater than 3.0 mg/l, respectively (p, 0.001). 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 (reference group), 1.5 (95% CI 1.0-2.2), 2.3 (1.6-3.3), and 4.0 (3.0-5.4), respectively. Conclusion: CRP is an independent predictor of future CV events among women with and without the metabolic syndrome.
