Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function - the Tromso study

Abstract

BackgroundPrevious studies have shown an association between impaired kidney function, assessed by cystatin C-based estimated glomerular filtration rate, and venous thromboembolism. The aim of this study was to investigate whether serum cystatin C was associated with a risk of venous thromboembolism among subjects with normal kidney function in a prospective population-based study. Design and MethodsCystatin C was measured in serum from 3251 men and women with normal kidney function, aged 25-84 years, who participated in the Tromsø study in 1994-1995. Normal kidney function was defined as a creatinine-based estimated glomerular filtration rate greater than 90 mL/min/1.73 m 2 and absence of microalbuminuria. Incident venous thromboembolism was registered from the date of inclusion through to the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios with 95% confidence intervals for venous thromboembolism. ResultsThere were 83 incident venous thromboembolic events, of which 53 (63.9 %) were provoked, during a median of 12.3 years of follow-up. A one standard deviation (0.11 mg/L) increase in serum cystatin C levels was associated with a 43% (hazard ratio 1.43; 95% confidence interval 1.17-1.72) increased risk of total venous thromboembolism. Subjects with cystatin C levels in the top quartile (≥0.87 mg/L) had a 2.5-fold (hazard ratio 2.51; 95% confidence interval 1.27-4.96) increased risk of venous thromboembolism compared to those with levels in the bottom quartile (≤0.72 mg/L) in adjusted analysis. The risk estimates were even higher for provoked venous thromboembolism (hazard ratio 3.11; 95% confidence interval 1.23-7.86). ConclusionsSerum cystatin C levels were associated with the risk of venous thromboembolism in subjects with normal kidney function. Our findings suggest that elevated serum cystatin C levels may promote venous thrombosis beyond reflecting impaired kidney function.Key words: cystatin C, venous thromboembolism, VTE, risk. 2012;97(7):1008-1013. doi:10.3324/haematol.2011 Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function -the Tromsø study Citation: Brodin EE, Braekkan SK, Vik A, Brox J, and Hansen J-B. Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function -the Tromsø study. Haematologica ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

Is Serum Cystatin C a Predictor of Acute Pulmonary Thromboembolism in Patients With Normal Renal Function?

“…28,29 In addition, increased cystatin C levels were also correlated with BMI and older age. 19,[30][31][32] The present study also shows that serum cystatin C levels were correlated with age, BMI, Scr, and eGFR in the total population in accordance with other previous reports. D-Dimer is formed when cross-linked fibrin is broken down by plasmin.…”

“…In a recent article, Brodin et al reported that 61.4% of the 83 patients with VTE had deep vein thrombosis and only 38.6% had PTE. 19 The authors showed that patients with serum cystatin C levels in the top quartile (≥0.87 mg/L) had a 2.5-fold increased risk of VTE compared to those with levels in the bottom quartile (≤0.72 mg/L) adjusted for age, sex, BMI, smoking, diabetes, and high sensitivity (hs)-CRP. 19 In addition, when analyzing cystatin C as a continuous variable, they found that an increase of 1 SD (0.11 mg/L) in cystatin C concentration was associated with a 46% increased risk of VTE.…”

“…In another report, Brodin et al analyzed 83 incident venous thromboembolic events in 3251 patients during a median of 12.3 years of follow-up. 19 They found that serum cystatin C levels were associated with the risk of venous thromboembolism in patients with normal kidney function. However, to the best of our knowledge, there are no reports in the literature comparing the serum cystatin C levels in patients with acute PTE and non-PTE.…”

Development and validation of risk prediction models for multiple cardiovascular diseases and Type 2 diabetes

“…Accurate risk assessment of an individual's propensity to develop CVDs is essential for personalized health care and primary prevention of these conditions. An increasing number of novel biomarkers have been linked to CVD risk [3][4][5][6][7][8][9][10][11][12][13][14], implying their critical role in precise risk assessment for heterogeneous CVDs. Current established functions for CVD risk stratification are either based only on conventional risk factors or include a limited number of biomarkers [15][16][17][18].…”

Prognostic value of cystatin C in acute coronary syndrome

“…Thus, it may be hypothesized that increased serum levels of cystatin C represent an inadequate counterbalancing mechanism to avoid thrombosis formation. [11][12][13][14][15][16][17] A recent study conducted by Urbonaviciene et al demonstrated that higher serum cystatin C levels independently predicted 5-year all-cause and CVS mortality in symptomatic peripheral arterial disease patients with normal renal function. In accordance with Urbonaviciene et al 18 Loew and colleagues 19 have reported that only high plasma cystatin C levels(> 1.24 mg/l) were associated with risk of fatal and nonfatal cardiovascular events during the follow-up.…”