Gender differences in the association of syndecan-4 with myocardial infarction: The population-based Tromsø Study


      • Syndecans shed from the endothelial glycocalyx may reflect early atherosclerosis.
      • In a general population serum syndecan-4 was associated with myocardial infarction.
      • The association was found in women only.
      • Syndecan-1 was not associated with cardiovascular disease after several years.


      Background and aims

      Cardiovascular disease is a common cause of morbidity and mortality, with gender differences in pathophysiology. The endothelial glycocalyx maintains vascular integrity, and glycocalyx shedding reflects endothelial dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the glycocalyx, and increased serum levels indicate glycocalyx damage. We hypothesised that increased serum syndecan-1 and -4 were independently associated with myocardial infarction (MI), ischaemic stroke and all-cause mortality in men and women from a general population.


      Using a case-cohort design, we included 1495 participants from the Tromsø Study 2001-02. Syndecan-1 and -4 were measured in serum. Baseline variables also included age, gender, cardiovascular risk factors and urinary albumin-creatinine ratio (ACR). Hazard ratios were assessed using multivariable Cox regression models.


      Between baseline in 2001-02 and December 2007 fatal or non-fatal MI was experienced by 328 and ischaemic stroke by 191 subjects, and 423 participants died. Syndecan-4 was independently associated with MI (hazard ratio per 10 ng/mL increase 1.32; 95% confidence interval 1.06–1.63), but not ischaemic stroke and mortality, and the associations were unchanged by adjustment for urinary ACR. Interaction between syndecan-4 and sex was borderline significant, and in gender-specific analysis, syndecan-4 was associated with MI in women only. Syndecan-1 was not associated with any endpoint.


      Syndecan-4 was associated with incident MI, and the association was stronger in women than in men. This suggests a link between endothelial glycocalyx shedding and coronary heart disease in women. Use of syndecan-4 as a risk marker in clinical setting needs further investigation.


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