Department of Medical Sciences (L.L., J.S.), Uppsala University, Sweden.
The George Institute for Global Health, University of New South Wales, Sydney, Australia (J.S.).
Circ Genom Precis Med. 2021 Apr;14(2):e002963. doi: 10.1161/CIRCGEN.120.002963. Epub 2021 Feb 26.
It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs.
The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used.
Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24-26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4-5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links.
During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.
已知某些心血管疾病（CVD）存在关联，如心房颤动和中风。然而，对于其他 CVD，其关联和时间趋势研究较少。在这项纵向研究中，我们研究了不同 CVD 之间的时间流行病学和遗传关联。
ULSAM（乌普萨拉成年男性纵向研究；2322 名 50 岁男性）在 40 年内对 4 种主要 CVD（心肌梗死、缺血性中风、心力衰竭和心房颤动）进行了随访。遗传分析使用了公开可用的数据。
使用多状态模型，发现所有 4 种研究 CVD 之间的对之间存在显著关系。然而，获得额外 CVD 的风险在不同 CVD 之间和其时间顺序之间存在显著差异。心力衰竭和心房颤动之间的关系显示出较高的风险比（风险比 24-26），无论时间顺序如何。心肌梗死和心房颤动之间也存在一致的关联，但相对风险较低（风险比 4-5）。相反，心肌梗死后诊断心力衰竭的风险比相反的时间顺序高近两倍（风险比 16 对 9）。与传统危险因素相关的遗传位点可以部分解释 CVD 之间的观察到的关联，但途径分析也揭示了其他病理生理联系。
在 40 年内，所有 4 种研究 CVD 相互之间存在关联，无论发生的时间顺序如何，但不同 CVD 和其时间顺序之间的风险大小存在差异。遗传分析揭示了 CVD 之间的新病理生理联系。
