LDL 胆固醇在老年仍是问题吗？一项孟德尔随机化研究。
LDL cholesterol still a problem in old age? A Mendelian randomization study.
机构信息
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Leyden Academy of Vitality and Ageing, Leiden, The Netherlands, Faculty of Health and Medical Sciences, Department of Public Health, University of Copenhagen, Copenhagen, Denmark, Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands and Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Leyden Academy of Vitality and Ageing, Leiden, The Netherlands, Faculty of Health and Medical Sciences, Department of Public Health, University of Copenhagen, Copenhagen, Denmark, Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands and Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Leyden Academy of Vitality and Ageing, Leiden, The Netherlands, Faculty of Health and Medical Sciences, Department of Public Health, University of Copenhagen, Copenhagen, Denmark, Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands and Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
出版信息
Int J Epidemiol. 2015 Apr;44(2):604-12. doi: 10.1093/ije/dyv031. Epub 2015 Apr 7.
BACKGROUND
Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underestimated. In the current study, we used an LDL genetic risk score (GRS) to overcome this problem.
METHODS
A weighted GRS was created using 51 single nucleotide polymorphisms associated with LDL-C levels. The LDL GRS was calculated in three Dutch cohorts: the Leiden Longevity Study (LLS) (n = 3270), the Leiden 85-plus study (n = 316) and the Rotterdam Study (n = 4035). We assessed the association between the LDL GRS and LDL-C levels, chronological age, familial longevity and mortality.
RESULTS
Up to 90 years of age, in each age stratum individuals with high LDL GRS had higher LDL-C levels (P = 0.010 to P = 1.1 x 10(-16)). The frequency of LDL-increasing alleles decreased with increasing age [β = -0.021 (SE = 0.01) per year, P = 0.018]. Moreover, individuals with a genetic predisposition for longevity had significantly lower LDL GRS compared with age-matched individuals of the general population [LLS nonagenarians vs > 90 years: β = 0.73 (SE = 0.33), P = 0.029, LLS offspring vs partners: β = 0.66 (SE = 0.23), P = 0.005]. In longitudinal analysis, high GRS was associated with increased all-cause mortality in individuals > 90 years, with a 13% increased risk in individuals with the highest LDL GRS (P-trend = 0.043).
CONCLUSION
Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity.
背景
在老年人中进行的观察性研究表明，胆固醇水平与死亡率之间无关联或呈负相关。然而，在老年时，由于反向因果关系，血浆低密度脂蛋白胆固醇（LDL-C）可能无法反映终生水平，因此风险可能被低估。在本研究中，我们使用 LDL 遗传风险评分（GRS）来克服这个问题。
方法
使用与 LDL-C 水平相关的 51 个单核苷酸多态性创建加权 GRS。在三个荷兰队列中计算 LDL GRS：莱顿长寿研究（LLS）（n=3270）、莱顿 85 岁以上研究（n=316）和鹿特丹研究（n=4035）。我们评估了 LDL GRS 与 LDL-C 水平、年龄、家族长寿和死亡率之间的关系。
结果
在 90 岁之前，每个年龄组中，LDL GRS 较高的个体 LDL-C 水平较高（P=0.010 至 P=1.1x10(-16)）。随着年龄的增长，增加 LDL 的等位基因的频率降低[β=-0.021（SE=0.01）/年，P=0.018]。此外，具有长寿遗传倾向的个体的 LDL GRS 明显低于一般人群中年龄匹配的个体[LLS 百岁老人与>90 岁：β=0.73（SE=0.33），P=0.029，LLS 后代与伴侣：β=0.66（SE=0.23），P=0.005]。在纵向分析中，高 GRS 与>90 岁个体的全因死亡率增加相关，LDL GRS 最高的个体风险增加 13%（P 趋势=0.043）。
结论
本研究结果表明，高 LDL-C 水平的遗传倾向会导致终生的死亡率，包括在最年长的人群中，并且有益的 LDL 遗传风险谱与家族长寿相关。
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