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Insufficient evidence to show causal relationship between cystatin C, CVD
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Mendelian randomization analyses do not suggest a causal relationship between cystatin C and CVD, researchers reported in the Journal of the American College of Cardiology.
Using mendelian randomization analyses, researchers combined data from 76,481 participants from 16 prospective cohorts with 37,126 measures of cystatin C as well as genetic data from 43 studies (n = 252,216) with 63,292 CVD events. The common variant rs911119 in CST3 was used to determine if cystatin C plays a causal role in CVD.
Although cystatin C concentrations showed a correlation for CVD risk after adjusting for potential confounders (RR = 1.82 per doubling of cystatin C; P = 2.12 x 10–14), there was no evidence for a causal relationship, with a causal RR for CVD of 1 per doubling of cystatin C (95% CI, 0.82-1.22) that differed from the observational estimate (P = 1.6 x 10–5).
The researchers also did not find a causal effect of cystatin C on any component of CVD.
“Our findings suggest that residual confounding (eg, by impaired renal function) and/or reverse causality, rather than a causal effect of cystatin C per se, likely explained the observational relationship between cystatin C and clinical events. As such, interventions aimed at lowering circulating cystatin C are unlikely to represent an effective means to prevent CVD,” Sander W. van der Laan, MSc, of the Laboratory of Experimental Cardiology at the University Medical Center of Utrecht in the Netherlands, and colleagues wrote.
Adeera Levin, MD, from the division of nephrology at the University of British Columbia, Vancouver, and James H. Lan, MD, of the nephrology and kidney transplantation unit at the University of British Columbia, wrote in a related editorial: “The fact that cystatin C may not be causally related to CVD should not be misinterpreted. Clearly, as demonstrated by these authors and others, it is a useful marker to predict worsening or new onset of CVD in a variety of populations. Predicting those who are at high risk of events is critically important for clinical trial enrollment and clinical practice. This paper in no way suggests that we should abandon the use of cystatin C for these risk stratification purposes, but instead cautions against the pursuit of therapeutic strategies that target lowering values of cystatin C, because it is a marker but not a target for intervention.” – by Tracey Romero
Disclosure: van der Laan, Levin and Lan report no relevant financial disclosures. Please see the full study for a list of the other researchers’ relevant financial disclosures.
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