Predictors of Subclinical Atheromatosis Progression over 2 Years in Patients with Different Stages of CKD

Abstract

Background and objectives: Ultrasonographic detection of subclinical atheromatosis is a noninvasive method predicting cardiovascular events. Risk factors predicting atheromatosis progression in CKD are unknown. Predictors of atheromatosis progression were evaluated in patients with CKD.

Design, setting, participants, & measurements: Our multicenter, prospective, observational study included 1553 patients with CKD (2009-2011). Carotid and femoral ultrasounds were performed at baseline and after 24 months. A subgroup of 476 patients with CKD was also randomized to undergo ultrasound examination at 12 months. Progression of atheromatosis was defined as an increase in the number of plaque territories analyzed by multivariate logistic regression.

Results: Prevalence of atheromatosis was 68.7% and progressed in 59.8% of patients after 24 months. CKD progression was associated with atheromatosis progression, suggesting a close association between pathologies. Variables significantly predicting atheromatosis progression, independent from CKD stages, were diabetes and two interactions of age with ferritin and plaque at baseline. Given that multiple interactions were found between CKD stage and age, phosphate, smoking, dyslipidemia, body mass index, systolic BP (SBP), carotid intima-media thickness, plaque at baseline, uric acid, cholesterol, 25-hydroxy vitamin D (25OH vitamin D), and antiplatelet and phosphate binders use, the analysis was stratified by CKD stages. In stage 3, two interactions (age with phosphate and plaque at baseline) were found, and smoking, diabetes, SBP, low levels of 25OH vitamin D, and no treatment with phosphate binders were positively associated with atheromatosis progression. In stages 4 and 5, three interactions (age with ferritin and plaque and plaque with smoking) were found, and SBP was positively associated with atheromatosis progression. In dialysis, an interaction between body mass index and 25OH vitamin D was found, and age, dyslipidemia, carotid intima-media thickness, low cholesterol, ferritin, and uric acid were positively associated with atheromatosis progression.

Conclusions: Atheromatosis progression affects more than one half of patients with CKD, and predictive factors differ depending on CKD stage.

Keywords: atherosclerosis; blood pressure; cardiovascular disease; carotid intima-media thickness; chronic kidney disease; follow-up studies; humans; renal insufficiency, chronic; smoking; vitamin D.

Figure 1.

Atheromatous disease progress more in patients with plaque at baseline than in patients without plaque at baseline. Boxplot showing the number of territories with plaque at baseline and after 24 months of follow-up according to the presence of plaque at baseline. The highest whisker indicates the last value that is less than or equal to the result of the standard formula percentile 75+1.5× interquartile range (IQR). Circles and stars represent readings that are outliers or far outliers, respectively (defined as higher than percentile 75+1.5×IQR or percentile 75+3×IQR, respectively). P<0.001 between progression in patients with plaque at baseline versus progression in patients without plaque at baseline.

Figure 2.

Percentages and 95% confidence intervals of patients who showed atheromatosis progression according to CKD progression after 24 months. P<0.001.

Figure 3.

Percentage of patients with progression of atheromatosis over 24 months according to basal plaque and CKD progression in CKD stages 3 and 4–5. P<0.001 between progression in patients with neither CKD progression nor plaque at baseline and progression in patients with CKD progression and plaque at baseline.