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Original research article
Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke
  1. John Berntsson1,
  2. J Gustav Smith2,3,4,
  3. Linda S B Johnson1,
  4. Martin Söderholm1,5,
  5. Yan Borné1,
  6. Olle Melander1,
  7. Marju Orho-Melander1,
  8. Jan Nilsson1,
  9. Gunnar Engström1
  1. 1 Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden
  2. 2 Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden
  3. 3 Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden
  4. 4 Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
  5. 5 Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Malmö, Sweden
  1. Correspondence to John Berntsson, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö 20502, Sweden; john.berntsson{at}


Objective Vascular endothelial growth factor D (VEGF-D) has important functions in lymphangiogenesis and angiogenesis. High plasma levels of VEGF-D have been associated with incidence of heart failure. The association of VEGF-D with atrial fibrillation (AF) and stroke is unclear and we hypothesised that VEGF-D could also be associated with incidence of AF and ischaemic stroke.

Methods VEGF-D was measured in fasting blood samples of 4689 subjects (40% men) without a history of AF from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Median age was 58 years (range 46–68). Cox regression analyses, adjusted for multiple risk factors, was used to assess AF and ischaemic stroke risk in relation to VEGF-D levels.

Results During a median follow-up time of 20.6 years, there were 637 cases of incident AF and 322 cases of first ischaemic stroke. After adjustment, VEGF-D was significantly associated with AF (HR 1.13(95% CI 1.04 to 1.23) per 1 SD increase) and ischaemic stroke (HR 1.14(95% CI 1.02 to 1.28) per 1 SD). The association with ischaemic stroke was explained by an increased incidence of AF-related stroke. HRs per 1 SD were 1.34 (95% CI 1.04 to 1.71) for AF-related ischaemic stroke and 1.04 (95% CI 0.90 to 1.19) for ischaemic stroke without AF.

Conclusions Increased VEGF-D concentrations were associated with AF and ischaemic stroke. The relationship with ischaemic stroke was more pronounced in subjects with a diagnosis of AF.

  • epidemiology
  • stroke
  • atrial fibrillation

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  • Contributors JPB, JGS and GE drafted the manuscript and performed the statistical analyses. All authors contributed to the conception and design of the work and interpretation of results. MS, OM, MOM, JN and GE contributed to the acquisition of data. All authors approved the final manuscript as submitted.

  • Funding This work was supported by the Swedish Heart-Lung Foundation, the Swedish Research Council, the European Research Council, the Crafoord Foundation, governmental funding of clinical research within the Swedish National Health Service and Skåne University Hospital.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The ethical committee at Lund University.

  • Provenance and peer review Not commissioned; externally peer reviewed.