BACKGROUND: Cross-sectional studies have reported seasonal variation in high-sensitivity C-reactive protein (hsCRP). However, longitudinal data are lacking.

METHODS: We collected data on diet, physical activity, psychosocial factors, physiology, and anthropometric measurements from 534 healthy adults (mean age 48 years, 48.5% women, 87% white) at quarterly intervals over a 1-year period between 1994 and 1998. Using sinusoidal regression models, we estimated peak-to-trough amplitude and phase of the peaks.

RESULTS: At baseline, average hsCRP was 1.72 mg/L (men, 1.75 mg/L; women, 1.68 mg/L). Overall seasonal variation amplitude was 0.16 mg/L (95% CI 0.02 to 0.30) and was lower in men (0.10 mg/L, 95% CI -0.11 to 0.31) than in women (0.23 mg/L, 95% CI 0.04 to 0.42). In both sexes, hsCRP peaked in November, with a corresponding trough in May. Relative plasma volume, waist and hip circumference, diastolic blood pressure, and depression scores were major factors associated with changes in amplitude of seasonal variation of hsCRP, and taken together explain most of the observed seasonal change. There was a 20% increase in the percentage of participants classified in the high-risk category for hsCRP (> or =3 mg/L) during late fall and early winter compared with late spring and early summer.

CONCLUSIONS: Concentrations of hsCRP were modestly increased in fall and winter compared to summer, with greater seasonal amplitude of variation observed in women. Conventional classification methods fail to consider seasonality in hsCRP and may result in substantial misclassifications in the spring and fall. Future clinical practice and research should take these variations into account.