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Cystatin C Is Not Causally Related to Coronary Artery Disease

Patrik Svensson-Färbom1, Peter Almgren2, Bo Hedblad2

  • 1Trelleborg Hospital, Department of Internal Medicine, Trelleborg, Sweden; Institution of Clinical Sciences, Lund University, Malmö, Sweden.

Plos One
|June 10, 2015
PubMed

Insights

Genetic factors influencing plasma cystatin C levels do not appear to causally affect coronary artery disease (CAD) risk. The observed association between cystatin C and CAD is likely explained by its relationship with estimated glomerular filtration rate (eGFR).

Area of Science:

  • Cardiovascular disease research
  • Genetic epidemiology
  • Biomarker analysis

Background:

  • Plasma cystatin C is independently associated with cardiovascular disease (CVD) risk.
  • This suggests a potential causal role for cystatin C in CVD pathogenesis.

Purpose of the Study:

  • To investigate the causal relationship between plasma cystatin C and coronary artery disease (CAD) risk.
  • Utilized a Mendelian Randomization approach to assess causality.

Main Methods:

  • Estimated the association between plasma cystatin C and CAD risk.
  • Assessed the association of a key cystatin C-related single nucleotide polymorphism (SNP), rs13038305, with plasma cystatin C levels.
  • Examined the relationship between rs13038305 and CAD risk in population-based cohorts (Malmö Diet and Cancer Study and CARDIOGRAM).

Main Results:

  • An increase in plasma cystatin C was associated with a higher risk of CAD (OR = 1.20).
  • The SNP rs13038305 strongly predicted higher plasma cystatin C concentrations (P<1 x 10-35).
  • However, rs13038305 was not significantly associated with CAD risk in pooled analyses (OR = 1.00, P = 0.83).

Conclusions:

  • Genetic predisposition to elevated plasma cystatin C does not alter CAD risk.
  • This indicates no direct causal link between plasma cystatin C and CAD.
  • The association between cystatin C and CAD is likely mediated by its relationship with estimated glomerular filtration rate (eGFR).
Abstract

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