Original Investigation
Pathogenesis and Treatment of Kidney Disease
Cystatin C and Carotid Intima-Media Thickness in Asymptomatic Adults: The Multi-Ethnic Study of Atherosclerosis (MESA)

https://doi.org/10.1053/j.ajkd.2008.06.025Get rights and content

Background

Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease.

Study Design

Cross-sectional study.

Setting & Participants

We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis.

Predictors

Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels.

Outcomes & Measurements

Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT.

Results

In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C–based estimated glomerular filtration rate less than 60 mL/min/1.73 m2, had no independent association with internal and common carotid IMT.

Limitations

There were few participants with severe kidney disease.

Conclusions

Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.

Section snippets

Participants

MESA is a community-based prospective cohort study designed to characterize subclinical cardiovascular disease and its progression. Its participants include 6,814 men and women free of clinical cardiovascular disease, aged 45 to 84 years, from 4 different self-reported ethnic groups (white, African American, Hispanic, and Chinese) recruited to meet prespecified race/ethnicity proportions. Participants were enrolled between July 2000 and August 2002 from 6 US communities (Baltimore, MD; Chicago,

Results

For the 6,557 participants, mean age was 62 years, 47% were men, and race/ethnicity distribution was 39% white, 27% African American, 22% Hispanic, and 12% Chinese. Mean cystatin C level was 0.89 ± 0.23 mg/L, and mean eGFR was 79 ± 18 mL/min/1.73 m2. Baseline characteristics of the study sample by quintiles of cystatin C level are listed in Table 1. Compared with participants in the lowest cystatin C quintile (≤0.74 mg/L), those in the highest cystatin C quintile (≥1.03 mg/L) were older, more

Discussion

In individuals without clinical cardiovascular disease, mild kidney impairment measured using cystatin C level was strongly associated with common and internal carotid IMT in unadjusted analyses. However, this relationship was accounted for predominately by age. We found no independent association between either cystatin C level or CKD with common or internal carotid IMT. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the

Acknowledgements

The authors thank the other investigators, staff, and participants of MESA for valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

Support: This research was supported by contracts N01-HC-95159 through N01-HC-95167 from the National Heart, Lung, and Blood Institute (NHLBI). Dr Shlipak is supported by R01 DK066488-01 and the American Heart Association Established Investigator Award. Dade Behring Inc donated to MESA

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    Originally published online as doi:10.1053/j.ajkd.2008.06.025 on September 29, 2008.

    Because the Editor-in-Chief recused himself from consideration of this manuscript, the peer-review and decision-making processes were handled entirely by a Co-Editor (Wolfgang C. Winkelmayer, MD, ScD, Harvard Medical School) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

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