NEW STUDY

Results

Relationship between SRH and suPAR levels. The participants had a median suPAR level of 3.4 ng/ mL (IQR: 2.7–4.3), and suPAR levels increased with worse SRH (Fig. 2). When reducing SRH into 3 categories, suPAR levels for participants reporting excellent/very good SRH were 3.2 ng/mL (IQR: 2.6–4.0), 3.4 ng/mL (IQR: 2.8–4.3) for those reporting good SRH, and 3.8 ng/mL (IQR: 3.1–4.9) for those reporting fair/bad SRH (Supplementary Table 2). Te number of participants within each of the SRH categories according to their suPAR category is also shown in Supplementary Table 2.

Individual and mutually adjusted associations of SRH and suPAR with the risk of acute hospitalization. Within 2 years after baseline examination, 437 (8.0%) participants were acutely hospitalized, 8 (0.2%) had died, and 10 (0.2%) were lost to follow-up. When suPAR levels were analyzed as a continuous variable, a doubling in suPAR levels was associated with a signifcantly higher risk of acute hospitalization both in unadjusted (Sub-distribution HR: 1.50, 95% CI: 1.27 to 1.78, P<0.0001) and adjusted (SDHR: 1.30, 95% CI: 1.06 to 1.59, P=0.011) analyses. The interaction between suPAR and sex was not statistically significant (P=0.46). In individual analyses of SRH and suPAR as 3-level categories, participants reporting good or fair/bad SRH, as well as those with intermediate or high suPAR, were at signifcantly higher risk of hospitalization compared to participants with excellent/very good SRH or low suPAR, respectively (Fig. 3A). Mutual adjustment for SRH and suPAR did not afect the strength of the associations (Fig. 3A). To further investigate whether SRH and suPAR were independently associated with the risk of acute hospitalization, we added an interaction term between suPAR and SRH categories to the mutually adjusted model. Te interaction term was not statistically signifcant, suggesting that the associations of suPAR or SRH categories with the risk of acute hospitalization are not signifcantly dependent on each other (P=0.62).

Methods

Study and participants. This study is based on data collected from participants from the Danish Inter99 cohort, a non-pharmacological intervention study for the prevention of ischemic heart disease consisting of 13,016 participants aged 30–60 years who were randomized to either a high or a low intervention of lifestyle counselling. Of these, 6784 agreed to participate and underwent a baseline examination between March 1999
and January 200146. Te examination included a clinical examination, extensive questionnaires assessing lifestyle, socioeconomic status, mental health, and SRH, as well as blood sampling. Participants were linked to the Danish health and social registers containing information on hospitalizations, ICD-10 codes, and death46,47. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Scientifc Ethics Committee of the Capital Region of Denmark (KA 98 155) and the Danish Data Protection Agency, and was registered as a clinical trial (ClinicalTrials.gov; NCT00289237). All participants provided written informed consent before taking part in the study. No efect of the lifestyle intervention was observed in the original study47, and we included all participants who had data available for both SRH and suPAR levels in the present study (n=5490, Fig. 1).

Self‑rated health. SRH was assessed at baseline via a self-administered questionnaire. The question was
formulated as: “How do you think your health is, all in all?”, with the following possible answers: “excellent”, “very good”, “good”, “fair”, or “bad”.

suPAR. Serum levels of suPAR (ng/mL) at baseline were measured using the suPARnostic ELISA assay (Virogates, Birkeroed, Denmark) as previously reported 36. Samples were measured in singlets, but according to the manufacturer of the suPARnostic ELISA, the intra‐assay variation is 2.8%, and the inter-assay variation as 9.2%. Samples with values below the detectable range of the assay (0.6 ng/mL) were excluded (n=13), and samples with values above the detectable range were assigned a value corresponding to the upper limit of quantifcation (22 ng/mL, n=2).