Oskarsson Viktor, Salomaa Veikko, Jousilahti Pekka, Palmieri Luigi, Donfrancesco Chiara, Sans Susana, Iacoviello Licia, Costanzo Simona, Ferrario Marco M, Cesana Giancarlo, Thorand Barbara, Peters Annette, Tunstall-Pedoe Hugh, Woodward Mark, Zeller Tanja, Blankenberg Stefan, Kuulasmaa Kari, Söderberg Stefan
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland.
PLoS One. 2025 Apr 24;20(4):e0319607. doi: 10.1371/journal.pone.0319607. eCollection 2025.
It has been hypothesized but seldom tested that the winter excess in cardiovascular disease (CVD) is related to hypovitaminosis D. The present study examined the association between CVD and (i) seasonality of 25-hydroxyvitamin D (25[OH]D) and (ii) individual 25(OH)D concentrations.
Harmonized 25(OH)D data were obtained from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, including 79,570 participants examined between 1984 and 2010. One 25(OH)D measurement was available per participant. Primary endpoints were CVD incidence (coronary heart disease or stroke; n = 6006) and CVD mortality (n = 2985). To study (i), Poisson regression-derived rate ratios were compared according to two-month categories, ordered by baseline 25(OH)D concentrations. To study (ii), Cox regression-derived hazard ratios were compared according to quarters of baseline 25(OH)D concentrations. With respect to (i), despite a median 25(OH)D concentration ratio of 1:1.79, the trough months of 25(OH)D in March and April had a similar CVD incidence as the peak months of 25(OH)D in August and September (rate ratio: 1.07, 95% CI: 0.98-1.17). CVD mortality was slightly higher in the trough months compared to the peak months (rate ratio: 1.27, 95% CI: 1.12-1.44) but not compared to the other months (despite median 25[OH]D concentration ratios up to 1:1.62; p ≥ 0.077). The CVD mortality peak in January preceded the 25(OH)D trough, not adhering to the temporality criterion of Bradford Hill. With respect to (ii), compared to the lowest quarter, the highest quarter of 25(OH)D was associated with lower CVD incidence (hazard ratio: 0.82, 95% CI: 0.76-0.89) and CVD mortality (hazard ratio: 0.64, 95% CI: 0.57-0.72).
The present study does not support the hypothesis that seasonal increases in CVD are driven by short-term reductions in 25(OH)D. As in most observational studies, higher 25(OH)D concentrations were inversely associated with CVD.
有假说认为心血管疾病（CVD）冬季高发与维生素D缺乏有关，但很少得到验证。本研究调查了CVD与（i）25-羟基维生素D（25[OH]D）的季节性变化以及（ii）个体25(OH)D浓度之间的关联。
从欧洲心血管风险评估生物标志物（BiomarCaRE）项目中获取了统一的25(OH)D数据，包括1984年至2010年间接受检查的79570名参与者。每位参与者有一次25(OH)D测量值。主要终点为CVD发病率（冠心病或中风；n = 6006）和CVD死亡率（n = 2985）。为研究（i），根据两个月的类别比较泊松回归得出的发病率比，按基线25(OH)D浓度排序。为研究（ii），根据基线25(OH)D浓度的四分位数比较Cox回归得出的风险比。关于（i），尽管25(OH)D的中位数浓度比为1:1.79，但3月和4月25(OH)D的低谷月份的CVD发病率与8月和9月25(OH)D的高峰月份相似（发病率比：1.07，95%CI：0.98 - 1.17）。低谷月份的CVD死亡率略高于高峰月份（发病率比：1.27，95%CI：1.12 - 1.44），但与其他月份相比无差异（尽管25[OH]D中位数浓度比高达1:1.62；p≥0.077）。1月的CVD死亡率高峰先于25(OH)D低谷，不符合布拉德福德·希尔的时间顺序标准。关于（ii），与最低四分位数相比，25(OH)D最高四分位数与较低的CVD发病率（风险比：0.82，95%CI：0.76 - 0.89）和CVD死亡率（风险比：0.64，95%CI：0.57 - 0.72）相关。
本研究不支持CVD季节性增加是由25(OH)D短期降低所驱动这一假说。与大多数观察性研究一样，较高的25(OH)D浓度与CVD呈负相关。
