The ULSAM study was initiated in 1970, and in 1970–74 2,322 men all aged 50 years living in the city of Uppsala, Sweden, were investigated as part of the Uppsala Longitudinal Study of Adult Men (ULSAM, http://www.pubcare.uu.se/ulsam) [15]. Of the invited men 82% accepted to participate. This cohort have since then been reinvestigated at ages 60, 70 and 77 years. All participants in ULSAM gave written informed consent, and the Ethics Committee of Uppsala University approved the study protocols. The study was conducted according to the Declaration of Helsinki.

The baseline examination of ULSAM in the early seventies when participants were 50 years old has been described in detail previously [6]. We included traditional cardiovascular (CV) risk factors, with LDL- and HDL-cholesterol, systolic blood pressure (SBP), BMI, diabetes, and smoking. Fasting blood samples were drawn in the morning after an overnight fast. Serum levels of cholesterol, triglycerides, and HDL were assayed by enzymatic techniques. Friedewald’s formula was used to calculate LDL-cholesterol. Moreover, fasting plasma glucose was measured using an oxidase method. Supine systolic and diastolic blood pressures were measured twice in the right arm after 10 min rest, and means were calculated. Data on smoking status at baseline was based on a questionnaire. BMI was calculated by weight/squared height.

Leisure time physical activity was assessed by a self-reported questionnaire at each examination. Participants answering yes to the question best reflecting their activity level graded from 1 to 4: (1) Mainly sedentary behavior (reading, watching television, or activities which do not need physical activity). (2) Walking or cycling (for pleasure walking, cycling, or some other form of physical activity for at least 4 h per week). (3) Recreational sports or heavy gardening for at least 3 h every week (exercises to keep fit, heavy gardening, etc., for at least 4 h per week). (4) Regularly engage in hard physical training (hard training or participation in competitive sports, regularly and several times a week). The questionnaire categories has previously been validated and used by other studies [16, 17].

VTE ICD-10 codes: I26, I80.2, I82.9; ICD-9 codes: 415.1 (415B), (416 W), (451X), (451B) (451 C), (453 W); ICD-8: 450, 452, 453. There was no loss of follow-up. The baseline examination was performed in 1970–1974 and data on cause-of-death and hospitalizations were obtained to December 31st, 2014, giving four decades of follow-up.

The analyses were conducted using Cox proportional hazard models using updated covariates for PA and risk factors at four occasions (50, 60, 70 and 77 years). The method of updated co-variates splits the time into intervals corresponding to the number of examinations. In this case the time is split into one 50 to 60 interval, one 60 to 70 interval, one 70-to-77-year interval and one interval from 77 years to censor date. Thus, each time interval is having its own “baseline” measurement of PA (and other covariates) and therefore it is only the actual level of PA that is the exposure during that time period, not the previous PA levels.

Time at risk was calculated from the date of examination until date of VTE end-point, date of death, or end of follow-up (31 December, 2014), whichever occurred first. PA was treated as an nominal variable with the sedentary group as referents and the other groups being compared to that referent. We added time-updated information on the traditional CV risk factors systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking to the models. We also investigated how much PA added to the discrimination of VTE obtained by the traditional CV risk factors by using logistic regression and area under the receiver operating curve (ROC), as an indication of the predictive value of PA, when added to a model with established cardiovascular risk factors.