Quantification of lower leg arterial calcifications by high-resolution peripheral quantitative computed tomography

Abstract

Vascular calcifications and bone health seem to be etiologically linked via common risk factors such as aging and subclinical chronic inflammation. Epidemiologic studies have shown significant associations between low bone mineral density (BMD), fragility fractures and calcifications of the coronary arteries and the abdominal aorta. In the last decade, high-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as in-vivo research tool for the assessment of peripheral bone geometry, density, and microarchitecture. Although vascular calcifications are frequently observed as incidental findings in HR-pQCT scans, they have not yet been incorporated into quantitative HR-pQCT analyses. We developed a semi-automated algorithm to quantify lower leg arterial calcifications (LLAC), captured by HR-pQCT. The objective of our study was to determine validity and reliability of the LLAC measure. HR-pQCT scans were downscaled to a voxel size of 250 µm. After subtraction of bone volumes from the scans, LLAC were detected and contoured by a semi-automated, dual-threshold seed-point segmentation. LLAC mass (in mg hydroxyapatite; HA) was calculated as the product of voxel-based calcification volume (mm3) and mean calcification density (mgHA/cm3)/1000. To determine validity, we compared LLAC to coronary artery calcifications (CAC), as quantified by multi-detector computed tomography (MDCT) and Agatston scoring in forty-six patients on chronic hemodialysis. Moreover, we investigated associations of LLAC with age, time on dialysis, type-2 diabetes mellitus, history of stroke, and myocardial infarction. In a second step, we determined intra- and inter-reader reliability of the LLAC measure. In the validity study, LLAC were present (>0 mgHA) in 76% of patients, 78% of patients had CAC (>0 mgHA). Median LLAC was 6.65 (0.08 – 24.40) mgHA and median CAC as expressed by Agatston score was 266.3 (15.88 – 1877.28). We found a significant positive correlation between LLAC and CAC (rho=0.6; p<0.01). Dialysis patients with type-2 diabetes mellitus (DM; 35%) and history of stroke (13%) had higher median LLAC than patients without those conditions (DM 20.0 fold greater, p=0.006; Stroke 5.1 fold greater, p=0.047;). LLAC was positively correlated with time on dialysis (rho=0.337, p=0.029), there was a trend towards a positive association of LLAC and age (rho=0.289, p=0.053). The reliability study yielded excellent intra- and inter-reader agreement of the LLAC measure (intra-reader ICC=0.999, 95% CI=0.998–1.000; inter-reader ICC=0.998, 95% CI=0.994–0.999). Our study indicates that the LLAC measure has good validity and excellent reliability. The use of HR-pQCT for the simultaneous evaluation of arterial calcifications, peripheral bone geometry, bone density, and bone microarchitecture should facilitate future research on osteo-vascular interactions and potential associations with cardiovascular events.

Cellular and Molecular Mechanisms of Chronic Kidney Disease with Diabetes Mellitus and Cardiovascular Diseases as Its Comorbidities

“…In diabetic patients, VC is commonly seen in coronary and vascular arteries of lower limbs ( 177 , 178 ). Monckeberg already described medial artery calcification in an autopsy series that was identified in older age, renal failure, and diabetes as the factors associated with calcifications ( 179 ).…”

Similarities in trabecular hypertrophy with site-specific differences in cortical morphology between men and women with type 2 diabetes mellitus

“…In addition, HR-pQCT images were reviewed for the presence of vascular calcifications, which were defined as linear or tubular hyperdensity zones of circular, semi-circular, or crescent-like shape, which corresponded to the anatomical territory of the anterior tibial artery, the posterior tibial artery, the radial artery, the ulnar artery, the interosseous branches, or smaller intramuscular or subcutaneous arterioles [34]. Skin calcifications or other non-vascular soft tissue calcifications were not included.…”

CML/RAGE signal induces calcification cascade in diabetes

“…China has the highest number of people with diabetes, which accounts for about one-third of the total number of diabetic patients worldwide [1]. Patients with diabetes commonly manifest vascular calcification, including intima and medial calcification, which are mainly distributed in the coronary artery and lower extremity vessels, respectively [2, 3]. A multi-center epidemiological study demonstrated that the risk of acute cardiovascular events in patients with calcification score >300 is significantly higher than those in patients with calcification score of 1–100 [4, 5].…”