Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Int J Epidemiol. 2020 Feb 1;49(1):205-215. doi: 10.1093/ije/dyz156.
A link between suboptimal fetal growth and higher risk of cardiovascular disease (CVD) is well documented. It has been difficult to assess the contribution of environmental versus genetic factors to the association, as these factors are closely connected in nuclear families. We investigated the association between offspring birthweight and CVD mortality in parents, aunts and uncles, and examined whether these associations are explained by CVD risk factors.
We linked Norwegian data from the Medical Birth Registry, the Cause of Death Registry and cardiovascular surveys. A total of 1 353 956 births (1967-2012) were linked to parents and one maternal and one paternal aunt/uncle. Offspring birthweight and CVD mortality association among all relationships was assessed by hazard ratios (HR) from Cox regressions. The influence of CVD risk factors on the associations was examined in a subgroup.
Offspring birthweight was inversely associated with CVD mortality among parents and aunts/uncles. HR of CVD mortality for one standard deviation (SD) increase in offspring birthweight was 0.72 (0.69-0.75) in mothers and 0.89 (0.86-0.92) in fathers. In aunts/uncles, the HRs were between 0.90 (0.86-0.95) and 0.93 (0.91-0.95). Adjustment for CVD risk factors in a subgroup attenuated all the associations.
Birthweight was associated with increased risk of CVD in parents and in aunts/uncles. These associations were largely explained by CVD risk factors. Our findings suggest that associations between offspring birthweight and CVD in adult relatives involve both behavioural variables (especially smoking) and shared genetics relating to established CVD risk factors.
胎儿生长不良与心血管疾病（CVD）风险增加之间存在关联，这一点已得到充分证实。由于这些因素在核心家庭中紧密相连，因此评估环境因素与遗传因素对这种关联的贡献一直具有挑战性。我们调查了子女出生体重与父母、姑、叔、姨的 CVD 死亡率之间的关系，并检验了这些关联是否可以用 CVD 危险因素来解释。
我们将挪威的医疗出生登记处、死因登记处和心血管调查的数据进行了关联。共有 1 353 956 例（1967-2012 年）出生的婴儿与父母和一位母亲及一位父亲的姑、叔、姨建立了联系。通过 Cox 回归的风险比（HR）评估了所有关系中子女出生体重与 CVD 死亡率之间的关联。在亚组中检验了 CVD 危险因素对关联的影响。
子女的出生体重与父母和姑、叔、姨的 CVD 死亡率呈负相关。与子女出生体重每增加一个标准差（SD）相关的 CVD 死亡率的 HR 在母亲中为 0.72（0.69-0.75），在父亲中为 0.89（0.86-0.92）。在姑、叔、姨中，HR 分别为 0.90（0.86-0.95）和 0.93（0.91-0.95）。在亚组中调整 CVD 危险因素后，所有关联均减弱。
出生体重与父母及姑、叔、姨的 CVD 风险增加相关。这些关联在很大程度上可以用 CVD 危险因素来解释。我们的研究结果表明，子女出生体重与成年亲属 CVD 之间的关联既涉及行为变量（尤其是吸烟），也涉及与既定 CVD 危险因素相关的共同遗传因素。
