Association between serum cystatin C level and hemodynamically significant aortic stenosis: a prospective cohort study

BACKGROUND: Cystatin C (CysC) is a cysteine protease inhibitor involved in proteins catabolism and plays an essential role in human vascular pathophysiology. CysC may also increase the risk of aortic stenosis (AS), but limited studies have reported on this association. This study aimed to investigate if elevated serum CysC levels are associated with hemodynamically significant AS. METHODS: Serum CysC levels were estimated in 4,791 participants, samples were collected in 1990−1992. The study population was divided into quintile groups. Follow-up continued in 2011–2013 when participants returned for echocardiography examination. Incidence of aortic valve disease (AVD) was ascertained by Doppler echocardiography through the end of 2013. AVD defined in hemodynamic progression was assessed and classified as aortic sclerosis, mild stenosis, and moderate-to-severe stenosis. RESULTS: Overall, a total of 4,791 participants (mean age: 54.8 ± 5.0 years, females: 57.6%, blacks: 8.2%) were included in this study. During a follow-up of 21 years, we identified 736 cases (15.4%) of aortic sclerosis, 194 cases (4.0%) of mild stenosis, and 42 cases (0.7%) of moderate-to-severe stenosis. Compared with serum CysC levels within individual quintile groups, the odds ratio (OR) was per standard deviation associated with an increased incidence of AVD (OR = 1.15, 95% CI: 1.05−1.26,P = 0.002). CONCLUSIONS: In this large population-based study, an increased serum CysC levels is independently associated with the incidence of hemodynamically significant AS. However, this association appears not to extend to patients with extremely high serum CysC levels and necessitate further investigation.