Life-Time Covariation of Major Cardiovascular Diseases: A 40 Year Longitudinal Study and Genetic Studies


Background - It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation (AF) 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 study (2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction (MI), ischemic stroke, heart failure (HF) and AF). For the genetic analyses, publicly available data were used. Results - Using multi-state modelling, significant relationships were seen between pairs of all of the four investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between HF and AF showed a high risk ratio (RRs 24-26) regardless of the temporal order. A consistent association was seen also for MI and AF, but with a lower relative risk (RRs 4-5). In contrast, the risk of receiving a diagnosis of HF following a MI was almost twice as high as for the reverse temporal order (RRs 16 vs 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 four 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.

Circulation: Genomic and Precision Medicine