To our knowledge, this is the first study to report seasonal variation of hsCRP in the general population using longitudinal data. The estimated seasonal amplitude of variation was greater among women, but the difference in amplitudes was not significantly different from that observed in men. The results also suggest that the magnitude of seasonal variation (10%–15%) is independent of the baseline hsCRP value. We also observed a 20% relative increase in the number of participants classified in the high-risk category for hsCRP (hsCRP values ≥3 mg/L) during the late fall and early winter, compared with late spring and early summer.
Our results are consistent with suggestions from previous cross-sectional studies reporting higher concentrations of hsCRP in the winter compared with the summer. A study in a large, healthy adult population in Korea (12 064 men and 6381 women, average age 47.2 years), reported that, on average, hsCRP concentrations were 0.25 mg/L higher in the winter than in the summer (1.76 vs 1.51 mg/L, respectively), suggesting that increased plasma hsCRP during the winter months could be related to the observed increased risk of cardiovascular events, and other conditions that are known to have seasonal peaks, ranging from the common cold to cancer (20
Another cross-sectional study performed in the UK, in 9377 middle-aged adults, showed a seasonal variation in hsCRP of about 9%, between a low value in the summer and a high value in the winter (32
). Our finding of a 20% relative increase in the number of patients labeled as being in the high hsCRP risk category between summer and winter, although not statistically significant, needs to be taken into account as another source of variability in hsCRP risk categorization. Clearly, if this were indicative of a more generalizable pattern, it would have important implications for a host of conditions with known seasonal periodicity and for treatments that are known to be affected by timing (31
). We found that there is much more variation among women than among men, yet the percentages increasing into the high-risk category are similar in both men and women. The discrepancy may be related to differences in the time distribution of CRP by sex.
Average concentrations of hsCRP appeared to be similar in men and women, as reported for the general US population (23
); however, the amplitude of seasonal variation in hsCRP was statistically significant only among women, and >2 times the magnitude of the estimated amplitude in men.
Significant advances have been made concerning the differential effects of cardiovascular risk factors as they relate to sex (34
). Diabetes and concentrations of HDL cholesterol and triglycerides have been found to have a greater impact on CHD risk in women than in men (35
). Greater variability in autonomic responses, particularly heart rate variability, is seen in women, and this variability has been associated with improved cardiovascular health (36
).We have reported that women appear to have greater seasonal variation of lipid concentrations than men (30
) and have observed a similar sex pattern of greater seasonal variation in other physiologic variables, including systolic blood pressure and relative plasma volume (). This raises the possibility that the greater variability in physiologic variables seen in women suggests an overall physiology that may be more adaptable to changing circumstances, a factor which we speculate might contribute in some way to the overall lower morbidity and incidence of chronic diseases in women and, concomitantly, a longer lifespan.
Factors significantly associated with seasonal variation of hsCRP included relative plasma volume and anthropometric factors. We have described (30
) the effect of a relative winter hemoconcentration, which could be related to the clustering of peak values of hemostatic coronary risk factors during the winter months. Seasonal variation in hsCRP may be another factor related to the excess CHD mortality in the winter compared to the summer (37
). The positive correlation between anthropometric measurements and hs-CRP has been described extensively (38
). In our study, waist and hip circumference, but also BMI, were positively correlated with changes in amplitude of seasonal variation of hsCRP. Similarly, depression scores (18
) and blood pressure levels (40
) have been correlated with hsCRP, and appear to also have differential correlation with seasonal variation of hsCRP, with higher depression scores and lower systolic and diastolic blood pressures correlating with higher amplitude of seasonal variation of hsCRP. Minor infectious or inflammatory processes also were correlated with change in amplitude of seasonal variation of hsCRP. Given that CRP is an acute-phase protein, it would be expected that hsCRP follows the seasonal pattern of a higher incidence of minor viral infections during the colder months (41
).We attempted to reduce this potential by excluding hsCRP measures >10 mg/L; however, the presence of minor infectious or inflammatory processes remained a significant predictor of seasonal variation of hsCRP.
Our study has several strengths, including the longitudinal design with multiple and detailed measurements of demographic, anthropometric, dietary, physical activity, psychosocial, physiologic, and blood parameters related to hsCRP concentrations. We were therefore able to determine the relative contribution of these factors to the seasonal variation in hsCRP concentrations. We also kept track of minor inflammatory and infections processes and controlled, to the extent possible, for these factors in the statistical analyses. Limitations include the derivation of our study participants from a volunteer sample, composed of primarily white, well-educated individuals living in central Massachusetts; therefore caution should be taken in extrapolating our results to other populations. An additional limitation is the relatively small number of hsCRP measures (5
) per subject, limiting analysis to the simplest seasonal models.
In conclusion, clinically significant seasonal variation in hsCRP was observed in this cohort of healthy adults. Women had greater seasonal variation than men, 14% vs 6% fluctuation between late spring and late fall, respectively. Relative plasma volume, anthropometric measurements, diastolic blood pressure, and depression scores are major factors correlated with seasonal variation of hsCRP, with differential magnitude of effect by sex. Together, the analyzed factors explained all the observed seasonal variation of hsCRP. Further research is needed to understand the biological mechanisms and clinical implications of higher concentrations of hsCRP during late fall/early winter and to determine the presence and potential connotations of seasonal variation of hsCRP among patients with established CHD and other chronic diseases including diabetes and cancer.