Relationship of Cystatin C and Hypertension in Type 1 Diabetes

Takeaway Points:

1. Serum cystatin C is associated with the incidence of hypertension in type 1 diabetes mellitus.
2. Subjects in this study who developed hypertension displayed higher serum cystatin C levels than normotensive subjects, but had similar serum creatinine and estimated GFR levels.
3. The relationship of cystatin C to the incidence of hypertension may be the result of other disease processes.
4. Further studies are needed to investigate the direct effect of cystatin C on incident hypertension in people without kidney disease.

Noting that researchers have hypothesized that the “early decline in kidney function defined by cystatin C” may be related to incident hypertension, and that serum cystatin C has also been shown “to be associated with the incidence of hypertension in the general population independent of chronic kidney disease as estimated by serum creatinine,” the authors examined “the relation of serum cystatin C to the incidence of hypertension over 15 years of follow-up in a cohort of persons with type 1 diabetes mellitus.”

In “Serum Cystatin C and the Incidence of Hypertension in Type 1 Diabetes Mellitus,” published in the January issue of the American Journal of Hypertension, the authors used data from participants with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). During that study, a total of 795 participants were examined as part of a 10-year follow-up, during which time investigators administered a structured interview that included questions on “sociodemographic characteristics, alcohol and smoking history, comorbidities, and medication use,” measured participants’ blood pressure, measured previously frozen samples of blood for cystatin C, and collected urine samples.

For the purposes of this study, hypertension was defined as a systolic BP of ≥140 mm Hg and/or a diastolic BP of ≥90 mm Hg and/or a history of hypertension with current use of antihypertensive medications.” Of the 795 participants, 734 had “information on hypertension status,” with 266 (36.2%) diagnosed with hypertension. Of the remaining 468 subjects without hypertension, due to a variety of factors only 365 were available for the analysis of the relationship of cystatin C with hypertension incidence.

The authors reported that subjects who developed hypertension during follow-up tended to be “older, had higher BMI, and were more likely to have higher serum total cholesterol levels and mean systolic and diastolic BP at baseline,” but “did not differ by duration of diabetes and mean glycosylated hemoglobin levels from people who remained normotensive.” The 15-year cumulative incidence of hypertension was 52.8%.

Subjects who developed hypertension had higher serum cystatin C levels and were “more likely to have microalbuminuria and gross proteinuria,” but did not differ by serum creatinine and estimated glomerular filtration rate (GFR) levels (using the Modification of Diet in Renal Disease [MDRD] equation) from people who did not develop hypertension. Further analysis of data showed that serum cystatin C at baseline “was associated with the incidence of hypertension after adjustment for gender and age,” and remained associated with the incidence of hypertension after adjusting for BMI, diabetes duration, glycosylated hemoglobin, and baseline systolic and diastolic BP. GFR estimate from serum cystatin C (but not GFR estimate by serum creatinine using the MDRD equation) was related with the incidence of hypertension. The association of cystatin C and incidence of hypertension was similar in subjects with kidney disease and in the overall cohort.

In their discussion of these results, the authors noted that even after controlling for age, sex, and other factors, “a higher serum level of cystatin C was associated with increased risk of incident hypertension,” an effect that although independent of the presence of chronic kidney disease, “may still be due to kidney disease as suggested by the association of GFR defined by cystatin C equation with increased risk of hypertension.” Thus, “the relation of serum cystatin C is likely due to its being a more precise and sensitive measure than serum creatinine levels in defining early kidney dysfunction related to hypertension incidence.” They also noted that they found no relationship between serum cystatin C and incident hypertension in people without chronic kidney disease, proteinuria, and microalbuminuria.

They concluded that these data “show an association of serum cystatin C with the 15-year incidence of hypertension in type 1 diabetes. Although it is likely due to cystatin C being a more sensitive measure of early chronic kidney disease, there may be other nonrenal mechanisms that explain this association.”