Patterns of systemic arterial calcification in patients with chronic critical limb ischemia and its relationship to the ankle-brachial index and survival

Chronic critical limb ischemia (CLI), the endstage of peripheral artery disease
(PAD) is associated with high rates of amputation and a high mortality (Abu
Dabrh et al., 2015; Bertele, Roncaglioni, Pangrazzi, Terzian, & Tognoni, 1999;
Dormandy & Rutherford, 2000; Norgren et al., 2007; Rutherford et al., 1997;
Teraa, Conte, Moll, & Verhaar, 2016). However, the cause for this poor
amputation free survival is unknown.
Recently it was shown that within the patients group with CLI a subgroup can
be identified that is at a very high risk for amputation and death. This group
is characterized by a high ABI or incompressible crural vessels (Aboyans et
al., 2011; Arain et al., 2012) (Spreen et al. 2017, JAMA in revision). This
subgroup with high ABI has also a higher risk for diabetes, chronic kidney
disease, heart failure (Criqui et al., 2014; Spreen et al., 2016). Lack of
vessel compressability is probably caused by calcification of the vessel wall
and fibrosis. It is now believed that there are two types of calcification. The
calcifications causing vessel wall imcompressability are probably medial
arterial calcifications (Ix, Miller, Criqui, & Orchard, 2012; Potier, Abi
Khalil, Mohammedi, & Roussel, 2011). Atherosclerosis in the intima that can
have more dotlike calcified lipid lakes. On the other hand, arteriosclerosis,
which is stiffening of the vessel wall, is caused by medial arterial
calcification and is frequently circular (Janzen & Vuong, 2001; Monckeberg,
1903; Mustapha & Diaz-Sandoval, 2014). The calcifications are found in CLI
patients are probably medial calcifications.
Research about relationship between cardiovascular disease events and vascular
calcification are mainly limited to the coronary and carotid arteries. In
coronary artery disease, the patterns of these vessel wall calcifications are
associated with increased cardiovascular morbidity (Criqui et al., 2014; Ehara
et al., 2004). Some of these patterns are of more clinical importance than
other (e.g. dotted patterns). There are only a few studies on CT angiography
plaque identification and the results of these studies do not all show
correlation with clinical outcome. For example, the extent of the calcification
in carotid plaques is not associated with cardiovascular outcome (Hellings et
al., 2010). Recently, also the meaning of crural calcifications was
investigated. Guzman et al showed that severe tibial artery calcification was
an excellent predictor for amputation (Feiring, 2008; Guzman et al., 2008), and
Lew showed that a high ABI or poorly compressible arteries are due to
calcification of these vessels and also related to a low amputation free
survival (Lew, Nicolosi, & Botek, 2015).
Thus far, to the best of our knowledge, there are no studies known about the
patterns of calcified vessels in other flow territories than peripheral
vessels. Also, the correlation with calcified vessel with on of its clinical
measurements, the ankle-brachial index (ABI), is not known. So, the aim of
our study is to visualize the pattern of vascular calcifiction in all
vascular beds and investigate whether they can explain the low amputation free
survival in CLI patients with a high ABI or incompressible vessels.
Second we want to correlate the calcification pattern in the crural vessels to
the ABI to explain the stiff vessel wall. We hope that this insight can lead
to effective risk-stratification of individual patients and possibly better
treatment.

The purpose of this study is to determine the patterns of vascular
calcification in 5 different vascular beds in patients with CLI and a high ABI
or incompressible vessels and compare these to the pattern found in CLI
patients with a low ABI.
As a secondary goal, we wanted to evaluate the relationship of these vascular
calcification patterns with the ABI.

This study has a prospective, descriptive design.

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