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Published on: May 31, 2016
Coronary artery calcification and aortic valve calcification in patients with kidney failure: a sex-disaggregated
Liam J Ward1,2, Agne Laucyte-Cibulskiene1,3, Leah Hernandez1
1Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86, Stockholm, Sweden.
Insights
Sex differences in kidney failure reveal distinct cardiovascular calcification patterns. In females, inflammation and oxidative stress link to coronary artery calcification, while males show associations with both coronary artery and aortic valve calcification.
Area of Science:
- Nephrology
- Cardiology
- Biomarkers
Background:
- Chronic kidney disease (CKD) significantly increases cardiovascular disease (CVD) risk.
- Sex differences exist in CKD progression: females are more prone to CKD, while males progress faster to kidney failure (KF).
- Calcific cardiovascular remodelling, including coronary artery calcification (CAC) and aortic valve calcification (AVC), is common in CKD, but sex-specific differences are understudied.
Purpose of the Study:
- To investigate sex differences in coronary artery calcification (CAC) and aortic valve calcification (AVC) among patients with kidney failure (KF).
- To identify potential sex-specific biomarkers associated with cardiovascular calcification in KF patients.
Main Methods:
- Utilized computer tomography (CT) scans from 321 kidney failure (KF) patients (214 males, 107 females) to assess CAC and AVC using the Agatston method.
- Collected baseline biochemical data, including plasma inflammation markers (IL-6, TNF, hsCRP) and advanced glycation end-products (AGEs) via skin autofluorescence.
- Performed sex-disaggregated and age-adjusted analyses to determine associations between calcification and clinical/biochemical variables.
Main Results:
- CAC scores were associated with age in both sexes.
- In males, CAC correlated with diabetes mellitus and CVD; in females, CAC correlated with IL-6, TNF, and AGEs.
- In males, AVC correlated with age and IL-6. In females, AVC analysis was limited due to low sample size, but CAC was linked to mortality independent of age.
Conclusions:
- Female KF patients showed associations between inflammatory burden, oxidative stress, and CAC.
- Male KF patients exhibited associations between oxidative stress and CAC, and inflammation and AVC.
- Findings suggest a sex-specific biomarker signature for cardiovascular calcification in kidney failure, potentially influencing cardiovascular complication development.
Background:
Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF.
Methods:
KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables.
Results:
Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010).
Conclusions:
In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF.
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