Background: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.Methods: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.Results: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.Conclusions: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.

中文翻译：

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主要心血管疾病的终生协变


背景：众所周知，某些心血管疾病（CVD）与之相关，例如心房颤动和中风。然而，对于其他 CVD，其联系和时间趋势的研究较少。在这项纵向研究中，我们调查了不同 CVD 之间的时间流行病学和遗传关联。方法：ULSAM（乌普萨拉成年男性纵向研究；2322 名 50 岁男性）对 4 种主要 CVD（心肌梗死、缺血性中风、心力衰竭和心房颤动）。对于遗传分析，使用了公开可用的数据。结果：使用多状态模型，所有 4 种研究的 CVD 之间都发现了显着的关系。然而，获得一种额外 CVD 的风险在不同 CVD 之间及其时间顺序之间存在显着差异。无论时间顺序如何，心力衰竭和心房颤动之间的关系都显示出高风险比（风险比，24-26）。心肌梗死和心房颤动也存在一致的关联，但相对风险较低（风险比，4-5）。相比之下，心肌梗塞后被诊断为心力衰竭的风险几乎是逆时间顺序诊断的两倍（风险比，16 比 9）。与传发生率，但不同 CVD 及其时间顺序之间的风险程度不同。 遗传分析揭示了 CVD 之间新的病理生理学联系。