Sunlight, Nutrition and Health Research Center, 1745 Pacific Ave., Suite 504, San Francisco, CA 94109, USA.
The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Nutrients. 2024 Nov 1;16(21):3759. doi: 10.3390/nu16213759.
Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the association (or "apparent effect") due to "regression dilution". Here, we evaluate how follow-up interval from baseline to "event" affects the relationship between baseline serum 25-hydroxyvitamin D [25(OH)D] concentration and the later incidence of stroke and major cardiovascular events (MACEs). Findings for the relative risk (RR) of stroke and MACEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke and nine studies for MACEs. Linear regression analyses were used to study data for follow-up periods of up to 10 years and for more than 10 years. For stroke, the linear regression fit for 1-10 years is RR = 0.34 + (0.065 × follow-up [years]), = 0.84, adjusted = 0.67, < 0.001. No significant variations in association were found for studies with follow-up periods of 10-20 years. For MACEs, the linear fit for 1-8.1 years is RR = 0.61 + (0.055 × follow-up [years]), = 0.81, adjusted = 0.59, = 0.03. The shorter the follow-up period, the greater the apparent effect of better vitamin D status in reducing risk of stroke and MACEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as great as the estimate based on average follow-up intervals for all studies. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MACEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MACEs, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D's role in reducing risk of stroke and MACEs could be considered causal on the basis of an evaluation of the evidence using Hill's criteria for causality in a biological system. Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MACEs prospectively and in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should, therefore, be recommended for everyone likely to be at risk for stroke or MACEs and indeed in the general population.
前瞻性队列研究对于研究生物分子状态如何影响不良健康结局的风险非常有用。不太为人所知的是，随着随访时间的延长，由于“回归稀释”，关联（或“表观效应”）会降低。在这里，我们评估了从基线到“事件”的随访间隔时间如何影响基线血清 25-羟维生素 D [25(OH)D]浓度与随后发生中风和主要心血管事件 (MACE) 的关系。 从主要来自欧洲国家和美国的前瞻性队列研究中，根据基线血清 25(OH)D 浓度绘制了中风和 MACE 相对风险 (RR) 的发现，以反映出与中风和 MACE 的关系。 对于 MACE，1-8.1 年的线性拟合是 RR = 0.61 + (0.055 × 随访 [年])， = 0.81，调整 = 0.59， = 0.03。 对于随访时间为 10-20 年的研究，未发现关联存在显著差异。对于 MACE，1-8.1 年的线性拟合是 RR = 0.61 + (0.055 × 随访 [年])， = 0.81，调整 = 0.59， = 0.03。 随访时间越短，维生素 D 状态较好降低中风和 MACE 风险的表观效应越大。此外，基于所有研究的平均随访间隔时间，发现最短随访时间的血清 25(OH)D 浓度越高，其表观效应是估计值的两倍多。已经发现了一些机制来解释为什么较高的血清 25(OH)D 浓度可以降低中风和 MACE 的风险。随机对照试验并未表明维生素 D 补充剂能显著降低中风或 MACE 的风险，这可能是因为当血清 25(OH)D 浓度低于 15 ng/mL（38 nmol/L）时，两种结局的风险迅速增加，而且在西方发达国家，很难招募到足够的浓度如此之低的参与者。尽管如此，基于使用 Hill 因果关系标准对生物系统中的因果关系进行的证据评估，可以认为维生素 D 降低中风和 MACE 风险是因果关系。 血清 25(OH)D 浓度高于 20 ng/mL 与前瞻性中风和 MACE 风险显著降低有关，并且具有明显的因果关系。因此，建议所有可能有中风或 MACE 风险的人以及一般人群将血清 25(OH)D 浓度提高到 >20 ng/mL。
