Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
J Clin Endocrinol Metab. 2012 Dec;97(12):4623-30. doi: 10.1210/jc.2012-2329. Epub 2012 Sep 26.
Although recent population-based studies suggest a U-shaped relationship between serum IGF-I concentration and all-cause mortality, the distribution of death causes underlying this association remains unclear. We hypothesized that high IGF-I levels associate with increased cancer mortality, whereas low IGF-I levels associate with increased cardiovascular disease (CVD) mortality.
Serum IGF-I levels were measured in 2901 elderly men (mean age 75.4, range 69-81 yr) included in the prospective population-based Osteoporotic Fractures in Men Study (Sweden) study. Mortality data were obtained from central registers with no loss of follow-up. The statistical analyses included Cox proportional hazards regressions with or without a spline approach.
During the follow-up (mean 6.0 yr), 586 of the participants died (cancer deaths, n = 211; CVD deaths, n = 214). As expected, our data revealed a U-shaped association between serum IGF-I levels and all-cause mortality. Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) associated with increased cancer mortality [hazard ratio (HR) = 1.86, 95% confidence interval (CI) = 1.34-2.58; and HR = 1.90, 95% CI = 1.37-2.65, respectively]. Only low serum IGF-I associated with increased CVD mortality (quintile 1 vs. quintiles 2-4, HR = 1.48, 95% CI = 1.08-2.04). These associations remained after adjustment for multiple covariates and exclusion of men who died during the first 2 yr of follow-up.
Our findings demonstrate that both low and high serum IGF-I levels are risk markers for increased cancer mortality in older men. Moreover, low IGF-I levels associate with increased CVD mortality.
尽管最近的基于人群的研究表明，血清 IGF-I 浓度与全因死亡率之间存在 U 型关系，但这种关联背后的死因分布尚不清楚。我们假设高 IGF-I 水平与癌症死亡率增加有关，而低 IGF-I 水平与心血管疾病（CVD）死亡率增加有关。
在前瞻性基于人群的男性骨质疏松性骨折研究（瑞典）中，测量了 2901 名老年男性（平均年龄 75.4 岁，范围 69-81 岁）的血清 IGF-I 水平。死亡率数据来自中央登记处，无随访丢失。统计分析包括 Cox 比例风险回归分析，包括或不包括样条方法。
在随访期间（平均 6.0 年），有 586 名参与者死亡（癌症死亡，n=211；CVD 死亡，n=214）。正如预期的那样，我们的数据显示血清 IGF-I 水平与全因死亡率之间存在 U 型关系。低血清 IGF-I 以及高血清 IGF-I（五分位 1 或 5 与五分位 2-4 相比）与癌症死亡率增加相关[风险比（HR）=1.86，95%置信区间（CI）=1.34-2.58；和 HR=1.90，95%CI=1.37-2.65，分别]。只有低血清 IGF-I 与 CVD 死亡率增加相关（五分位 1 与五分位 2-4 相比，HR=1.48，95%CI=1.08-2.04）。这些关联在调整了多个协变量并排除了随访前 2 年内死亡的男性后仍然存在。
我们的研究结果表明，低血清 IGF-I 和高血清 IGF-I 水平都是老年男性癌症死亡率增加的风险标志物。此外，低 IGF-I 水平与 CVD 死亡率增加有关。
