New paper – Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study.

Overview of the “long” timeline of the CHS data collection, taken from the paper discussed.

The newest addition to our publications is this paper on the role of high levels of coagulation factor VIII and cognitive function, as well as white matter intensities in the brain. The theory behind is that since hypercoagulability is related to young, overt, stroke, would hypercoagulability perhaps also be linked to non-overt cerebrovascular mishap? Hypercoagulability here is measured as high levels of FVIII, one of the most potent risk factors for thrombosis, and the cerebrovascular mishap is the presence and intensity of white matter lesions. This paper has a long history in three very different, but meaningful ways.

The first “long”aspect is that you need to have a very long, and complex, follow-up to study this. Where clinical stroke is a sudden onset type disease, what were are studying in this project has a for more gradual character. So not months, but years. Decades even! And not a lot of studies have the prerequisites to study this question: first there must be the possibility to measure FVIII, which means citrate. But most long term follow-up studies do not have citrate. Second, there must be MRI data available throughout the study. However, most large longitudinal studies only have MRI at baseline as an exposure measure. Third, The studies must go on for a very long time, which comes with the complication that often the participation in these type of studies can dwindle over the years. So, all in all, there was really only one cohort who had all the data already collected and ready to analyze: the Cardiovascular Health Study. So we requested access to the data with a focus on FVIII, cognitive functioning and multiple measures of white matter lesions in order to assess worsening of lesions and were ready to analyze!

Interestingly, this brings us to the second “long” aspect of this paper – getting acces to and using the CHS data. The idea for this paper came roughly in 2013, when I got in touch with some CHS researchers for the first time. That is a long time ago from today, end of 2020. So what took us so long? Well first there was the move to Berlin. I decided to take this project me, but immigrating to a different country and starting a new job at the same tends to put some delays on ongoing projects. A second reason is that the CHS data is open for non CHS researchers to use, under one very strict condition – CHS researchers don’t just hand our data but they help you set up and execute your plan. This approach is not completely “open science” but it might be better. After all, it does ensure that the knowledge and experience that comes from actually collecting the data is taken into account when you prepare for and actually analyze the data. But that process takes time, especially when working with collaborators several time zones away.

A third and final “long” aspect was the time between first time submission and final publication. Our paper got rejected by 4 different journals before we got accepted at PLOS one. This is definitely not a record, but the delay isn’t pretty. The reasons for rejection were different at these journals, but the fact that this was a “null” finding in a general population cohort did certainly not help.

The paper, with the title “Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study” is published in PLOS One. You can also find it at the usual places. JLR took the lead of the project after I moved to Berlin, masterfully navigating and combining all the comments and input from this group of co-authors. Well done to all.