Abstract
Dickkopf-3 (DKK3) is an emerging biomarker for cardiovascular disease (CVD) and chronic kidney disease (CKD). Herein, baseline DKK3 plasma levels were measured in 8420 subjects from the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, a large general population cohort, using enzyme-linked immunosorbent assays. Associations with clinical variables and outcomes were analysed. Median DKK3 level was 32.8 ng/ml (28.0–39.0). In multivariable linear regression analysis, the strongest correlates for plasma DKK3 were age, body mass index and estimated glomerular filtration rate (eGFR). At baseline, 564 (6.7%) subjects had CVD (defined as a myocardial infarction and/or cerebrovascular accident) and 1361 (16.2%) subjects had CKD (defined as eGFR < 60 ml/min/1.73m2 and/or urinary albumin excretion (UAE) > 30 mg/24 h). Of subjects with known CVD and CKD follow-up status (respectively 7828 and 5548), 669 (8.5%) developed CVD and 951 (17.1%) developed CKD (median follow-up respectively 12.5 and 10.2 years). Crude logistic regression analysis revealed that DKK3 levels were associated with prevalent CVD (Odds ratio: 2.14 [1.76–2.61] per DKK3 doubling, P < 0.001) and CKD (Odds ratio: 1.84 [1.59–2.13] per DKK3 doubling, P < 0.001). In crude Cox proportional hazard regression analysis, higher DKK3 levels were associated with higher risk for new-onset CVD (Hazard ratio: 1.47 [1.13–1.91] per DKK3 doubling, P = 0.004) and CKD (Hazard ratio: 1.45, [1.25–1.69] per DKK3 doubling, P < 0.001). However, these associations remained no longer significant after correction for common clinical variables and risk factors, though independently predicted for new-onset CKD in a subgroup of subjects with the lowest UAE values. Together, DKK3 plasma levels are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD and only predicted for new-onset CKD in those subjects with the lowest UAE values.
Highlights
With the ageing population, diseases associated with life style including amongst others cardiovascular disease (CVD) and chronic kidney disease (CKD) are expected to become more prevalent
DKK3 levels were determined in plasma samples from 8420 subjects included in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort
We investigated the associations of Dickkopf-3 (DKK3) plasma levels with cardiovascular risk factors, cardiovascular disease (CVD) and chronic kidney disease (CKD) in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, which is a cohort with community-dwelling subjects designed to study cardiovascular risk factors and renal function, as well as both prevalent and new-onset CVD and C KD17
Summary
Diseases associated with life style including amongst others cardiovascular disease (CVD) and chronic kidney disease (CKD) are expected to become more prevalent. The protein DKK3 gained attention as an emerging biomarker for cardiovascular and renal diseases. In patients with pre-existing CKD, elevated urinary DKK3 levels at baseline improved existing risk prediction models for loss of kidney function[14]. In a large cohort of heart failure (HF) patients, plasma DKK3 levels were associated with several cardiovascular risk factors, including kidney function, atrial fibrillation, body mass index (BMI) and blood pressure[16]. We measured DKK3 plasma levels in 8420 subjects of the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, which is a cohort with community-dwelling subjects designed to study cardiovascular risk factors and renal function, as well as prevalent and new-onset CVD and CKD. The associations of DKK3 plasma levels with cardiovascular risk factors, and with both prevalent and new-onset CVD and CKD were determined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
