Cystatin C Predicts Incident Cardiovascular Disease in Twins

Abstract

BackgroundCystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors.Methods and ResultsThe predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox‐regression model during a median follow‐up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow‐up were identified and within‐pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47–1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25–1.70), ASCVD hazard ratio 1.26, 95% CI (1.13–1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01–1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co‐twin (1.11±0.3 mg/L versus 1.06±0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co‐twins (76.1±16.9 μmol/L versus 79.4±20.3 μmol/L).ConclusionsVariation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end‐organ damage and small‐vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease‐discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.

Cystatin C as a biomarker of chronic kidney disease: latest developments

“…The largest body of work, however, has been examining the association between cystatin C and cardiovascular disease. Rising cystatin C values are associated with the development and progression of cardiovascular disease (CVD), independent of renal function and other cardiovascular risk factors [65][66][67][68][69][70][71]. Cystatin C also has been found to hold prognostic value for procedure related outcomes [72][73][74][75][76], critical illness [44,77], and CVD and all cause mortality in both CVD patients [78][79][80][81] and the general population [82].…”

Serum cystatin C predicts the risk of non-ST-elevation acute coronary syndrome

“…Recent studies have shown that serum cystatin C (Cys-C) is closely associated with CAD [ 3 , 4 ]. Cys-C was an independent predictor of cardiac events, and could be an indicator of CAD severity [ 5 , 6 ].…”

Joint Associations of Pregnancy Complications and Postpartum Maternal Renal Biomarkers With Severe Cardiovascular Morbidities: A US Racially and Ethnically Diverse Prospective Birth Cohort Study

“… 14 , 15 It has been reported to be a useful biomarker for the detection of preeclampsia. 16 , 17 Available studies have demonstrated that impaired renal function, as assessed by serum levels of creatinine 10 , 18 , 19 , 20 or CysC, 10 , 18 , 21 , 22 , 23 , 24 , 25 predicts future CVD. However, most of these studies were conducted in nonpregnant older women, and limited data are available to address the role of these renal biomarkers measured shortly after delivery on severe maternal CVD morbidities later in life, individually and in combination with pregnancy complications.…”