Hindawi

Cardiology Research and Practice

Volume 2022, Article ID 5108389, 8 pages
https://doi.org/10.1155/2022/5108389

Research Article
Radial Artery Calcification in Predicting Coronary Calcification
and Atherosclerosis Burden

Alexandru Achim ,1,2 Kornél Kákonyi,1 Ferenc Nagy,1 Zoltán Jambrik,1 Albert Varga,1
Attila Nemes,1 Jeffrey Shi Kai Chan ,3 Gabor G. Toth ,4 and Zoltán Ruzsa 1
1
Second Department of Internal Medicine, Division of Invasive Cardiology, University of Szeged, Szeged, Hungary
2
“Niculae Stancioiu” Heart Institute, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
3
Heart Failure and Structural Heart Disease Unit, Cardiovascular Analytics Group, Hong Kong, China
4
University Heart Center Graz, Department of Cardiology, Medical University of Graz, Graz, Austria

Correspondence should be addressed to Alexandru Achim; dr.alex.achim@gmail.com

Received 14 March 2022; Revised 3 May 2022; Accepted 17 May 2022; Published 31 May 2022

Academic Editor: Fanbo Meng

Copyright © 2022 Alexandru Achim et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Background. Atherosclerosis is a systemic arterial disease with heterogeneous involvement in all vascular beds; however, studies
examining the relationship between coronary and radial artery calcification are lacking. The purpose of this study was to assess the
relationship between the two sites and the prognostic value of radial artery calcification (RC) for coronary artery disease. Methods.
This is a single-center, retrospective cross-sectional study based on Doppler ultrasound of radial artery (RUS) and coronary artery
angiography (CAG). We included a total of 202 patients undergoing RUS during distal radial access and CAG at the same
procedure, between December 2020 and May 2021, from which 103 were found having RC during RUS (RC group) and 99 without
(NRC group). Coronary calcifications were evaluated either by angiography examination (moderate and severe), positive CT
(>100 Agatson units), or intracoronary imaging (IVUS, OCT). Results. A significant correlation was observed between radial
calcification and coronary calcification variables (67.3% vs. 32.7%, p  0.001). The correlation between risk factors such as age,
smoking, chronic kidney disease, and diabetes mellitus was higher while sex did not play a role. The need of PCI and/or CABG was
higher in the RC group (60% vs. 44%, p  0.02). RC, therefore, predicts the extent and severity of coronary artery disease.
Conclusion. RC may be frequently associated with calcific coronary plaques. These findings highlight the potential beneficial
examination of radial arteries whenever CAD is suspected.

1. Introduction the general population [4, 5]. There also seems to be a strong
association between carotid and coronary stenosis [6–9].
Asymptomatic individuals with significant coronary artery While carotid examination in CAD and vice versa has become
disease (CAD) are at risk of unanticipated cardiac events of clinical importance in order to accurately identify patients
including myocardial infarction (MI). Laboratory studies, who could benefit from aggressive preventive therapies as well
stress tests, and coronary artery imaging including coronary as timely treatment, no relationship between radial and
artery calcification (CAC) scoring are used for evaluating at- coronary arteries has been investigated. Based on the shared
risk individuals. CAC scoring has been demonstrated to not underlying atherosclerosis pathology in the two arterial
only show current coronary disease but also predict future systems, this study aimed to explore whether the extent of
cardiac events [1–3]. Coronary artery calcification and cardiac calcifications in the two arteries is correlated and if RC is a
valve calcific deposits correlate well and predict mortality in parameter for predicting CAD.
2 Cardiology Research and Practice

202 SUBJECTS

HAND ULTRA SONOGRAPHY

RADIAL CALCIFICATION GROUP NORMAL RADIAL GROUP

103 SUBJECTS 99 SUBJECTS

Time to find artery (sec) Coronary calcium assesment Age, Sex

Number of attempts Smoking
Total access time 1. Radiopacities on angiography Diabetes Mellitus
2. +100 Agatson units on CTA
Pain score [1-5] 3. IVU S/OCT calcium HTN
Artery occlusion CKD Stage 3-5

Figure 1: Study design and patient selection. Inclusion in each group was done blindly and retrospectively.

2. Methods particular attention given to the type and extent of calcium

deposition (diffuse vs. nodular, medial vs. intimal). RC was
2.1. Study Population and Design. From December 2020 to visually assessed accordingly, assigning scores in each of two
May 2021, 202 consecutive patients who underwent coro- calcification categories based on ultrasound findings, as
nary angiography and who required radial Doppler ultra- follows: longitudinal involvement, 0 � no calcification,
sound examination were recruited in the study. All patients 1 � focal calcification, and 2 � diffuse calcification; density,
from this period who came to our catheterization laboratory 0 � no calcification, 1 � light calcification, and 2 � dense
for various transcatheter procedures were included, in the calcification. The designation of light versus dense calcifi-
context in which they received standardized pre- and cation was purely qualitative. A calcification index was
postoperative RUS evaluation of the radial artery [10–12]; derived and patients with a score of minimum 2 pcts were
the only inclusion criterion was therefore the invasive considered positive and included in the RC group. Only
cardiovascular evaluation, where the ultrasound images clear echoreflective areas with acoustical shadowing asso-
were clear, conclusive, and could be noted retrospectively. ciated with calcific plaques, as exemplified in Figure 2, were
Design of the study is presented in Figure 1. The 2 groups included.
were divided, according to the sonographic result at the level As step two, quantitative analysis of the angiographic
of the radial artery. Coronary status was analyzed as a follow- images was performed by a single individual blinded to the
up. A correlation was made between the two arterial systems, ultrasound results. Positive coronary calcification was de-
with emphasis on the most relevant risk factors and the fined as one of the following: (1) on angiography, radio-
coronary outcome. pacities readily visible but mild degree and/or obvious, heavy
calcification seen without cardiac motion, before contrast
injection; (2) on cardiac CT, calcium score above 100
2.2. Calcification Assessment. All patients underwent RUS- Agatson units; (3) during intracoronary imaging (IVUS,
assisted distal radial puncture, as per center’s protocol, OCT), the presence of an arc of calcium >180°, length
scanning the artery at the anatomical snuffbox area, using a >5 mm, and calcium thickness >0.5 mm.
7.5 MHz probe. Cross sections of the radial artery were Significant CAD was defined by the need of PCI and/or
assessed using the following factors: lumen diameter, vessel CABG. Additional risk factors (age, sex, smoking, diabetes
diameter, plaque distribution, and percent plaque area, with mellitus, primary hypertension, and renal failure) and radial
Cardiology Research and Practice 3

(a) (b) (c) (d)

Figure 2: Ultrasound scanning of the distal radial artery, showing normal aspect (a) and calcific deposits within the vessel wall (yellow
arrows), organized as calcific nodules (b), calcific plaques (c), and diffuse mediocalcinosis (d).

access performance indexes (time to find artery [sec], higher frequency of renal calcinosis (69.23%, 45/65) than the
number of attempts, access time [sec], pain score [1–5], and patients without renal failure (42.33%, 58/137), the differ-
artery occlusion) were analyzed. ence being statistically significant (p � 0.001). A statistically
significant correlation was established between the presence
of renal calcinosis and diabetes (55.97%, 89/159 vs. 32.55%,
2.3. Statistical Analysis. Continuous variables were 14/43, p � 0.001). No statistically significant correlations
expressed as mean ± standard deviation. Statistical analyses between either hypertension or artery occlusion and the
were performed using IBM SPSS v26.0 (Chicago, IL, USA). presence of radial calcinosis were found.
Correlations between dichotomious variables were per- Afterwards, a multivariable logistic regression analysis
formed using the Pearson Chi Squared test, or Fisher’s test. was performed (Table 4), demonstrating that age over 60
Median values between the two groups were compared using (p � 0.001, OR 3.4, 95% CI), smoking (p � 0.03, OR � 4.9,
Mann–Whitney U test. A multivariable logistic regression 95% CI), renal failure (p � 0.01, OR � 2.3, 95% CI), and
analysis was performed to identify independent predictors of diabetes (p � 0.03, OR � 2.3, 95% CI) were independently
RC. All p values were two-sided, and p < 0.05 was consid- associated with radial calcinosis.
ered statistically significant. A series of parameters involved in the performance of
Written informed consent was obtained from all pa- the radial puncture were compared between the two groups.
tients, and the Institution’s Ethics Committee approved the The mean value of the time to find artery was significantly
study. higher in the patients who presented radial calcinosis
(median time 3 minutes vs. 2 minutes, p � 0.01). There were
3. Results no statistically significant differences regarding the number
of attempts, access time, or pain score (Table 5).
Baseline characteristics are presented in Table 1. There was
no difference in sex across the two groups, but the mean age 4. Discussion
of the RC group was significantly higher (69.24 ± 9.80 years
vs. 63.35 ± 11.59 years, p � 0.001). The full spectrum of The main findings of our study were (1) significant corre-
patients was included but the main indication for coronary lation between radial and coronary calcification in adults
angiography remained to be stable angina (40%). presenting with angina symptoms and associated risk factors
Representative duplex ultrasound images of normal and and (2) the rate of revascularization treatment was higher in
calcified radial arteries are shown in Figure 2. The normal this population, suggesting the potential of radial artery
artery (Figure 2(a)) is characterized by a thin, homogeneous calcification to become a new marker of prediction of severe
wall and a smooth, luminal surface. Calcifications coronary artery disease.
(Figure 2(b)–2(d)) appear as echoreflective areas within the Based on our study, we suggest that incidental findings of
vessel wall (not to be confused with tissue streaking seen in upper extremity artery calcification on routine radiographs
the soft tissues of both normal and calcific studies) and are or Doppler ultrasound may warrant systemic evaluation for
associated with acoustical shadowing. The calcified vessel in atherosclerosis in other areas of the body, especially
Figures 2(b)–2(d) is narrower in caliber and exhibits an screening for CAD. Increasing RC occurrence correlated
irregular luminal surface. with CAC, but more importantly with more advanced CAD
There was a statistically significant association between (60% rate of PCI/CABG in the RC group vs. 44% in the NRC
the presence of radial calcinosis and coronal calcification group). Latest European prevention guidelines state that
(p � 0.001). The usage of PCI and/or CABG was signifi- CAC scoring may be considered to improve risk classifi-
cantly higher in the patients with radial calcinosis (p � 0.02) cation, and plaque detection by carotid ultrasound is an
(Table 2). alternative when CAC scoring is unavailable or not feasible
Several comorbidities were evaluated. An unadjusted (level of recommendation IIb) [13]. Thus, the theory of
analysis was performed to establish the risk factors involved including RUS as another alternative is attractive.
in the presence of the radial calcinosis (Table 3). Out of a Risk factors seem to play a role for arterial calcification.
total of 19 smokers, 16 (84.21%) of them presented radial Our study confirmed that radial calcinosis is more frequently
calcinosis (p � 0.001). Patients with renal failure had a found in population above 60 years, smokers, diabetics,
4 Cardiology Research and Practice

Table 1: Baseline characteristics of all 202 patients.

Mean ± SD/N (%)
Demographic features p value
RC group (n � 103) Non-RC group (n � 99)
Age (years) 69.24 ± 9.80 63.35 ± 11.59 0.07
Gender: female/male, % (n) 43.6% (45)/56.3% (58) 40.4% (40)/59.6% (59) 0.44
Height (cm) 169.4 ± 8 169.05 ± 5 0.92
Weight (kg) 84 ± 15 87 ± 16 0.23
Prior Comorbidities
Atrial fibrillation 17 (16.5%) 21 (21.2%) 0.39
Renal failure 45 (43.6%) 20 (20.2%) 0.003
Diabetes mellitus 89 (86.4%) 70 (70.7%) 0.006
Hypertension 45 (43.6%) 33 (33%) 0.13
Smoking 16 (15.5%) 3 (3.03%) 0.002
Family History 14 (13.6%) 11 (11.1%) 0.59
Dyslipidemia 29 (28.1%) 23 (23.2%) 0.42
Previous MI 12 (11.65%) 10 (10.1%) 0.72
Previous CABG 8 (7.7%) 3 (3.03%) 0.13
Indication for Catheterization
Stable angina 42 (40.7%) 40 (38.8%) 0.95
Unstable angina 12 (11.6%) 8 (8.08%) 0.39
NSTEMI 22 (21.3%) 17 (17.1%) 0.45
STEMI 8 (7.7%) 14 (14.1%) 0.14
Heart failure 3 (2.9%) 2 (2.02%) 0.92
Severe aortic stenosis 5 (4.8%) 7 (7.07%) 0.45
Peripheral interventions 6 (5.8%) 8 (8.08%) 0.55
Other 9 (8.7%) 3 (3.03%) 0.32
CABG: coronary artery bypass graft; MI: myocardial infarction; NSTEMI: non-STelevation myocardial infarction; RC: radial artery calcification; SD: standard
deviation; and STEMI: ST elevation myocardial infarction.

Table 2: Association between the presence of coronary calcification and presence of radial calcinosis (top). Association between the usage of
PCI and the presence of radial calcinosis (bottom).
Parameters Radial calcinosis No radial calcinosis p value
Present 68 33
Coronary calcification 0.001
Absent 35 66
Used 62 44
PCI/CABG 0.02
Not used 41 55
CABG: coronary artery bypass graft; PCI: percutaneous coronary intervention.

Table 3: Unadjusted analysis of the risk factors involved in the presence of radial calcinosis.
Parameters Radial calcinosis No radial calcinosis p value
Smoker 16 3
Smoking 0.001
Non-smoker 87 96
Absent 58 79
Renal failure 0.001
Present 45 20
Absent 14 29
Diabetes 0.001
Present 89 70
Absent 58 66
Hypertension 0.08
Present 45 33

Table 4: Multivariable logistic regression analysis of the risk factors involved in the presence of radial calcinosis.
B S.E. Wald df Sig. Odds ratio Confidence interval
Age over 60 1.236 0.371 11.091 1 0.001 3.443 3.102–3.774
Smoking 1.453 0.669 4.711 1 0.03 4.875 3.921–6.118
Renal failure 0.855 0.346 6.095 1 0.014 2.352 2.091–2.797
Diabetes 0.845 0.402 4.424 1 0.035 2.328 1.762–3.111
Hypertension 0.579 0.311 3.294 1 0.07 1.764 1.394–2.122
B � beta coefficient; S.E. � standard error; Wald � the Wald test; df � degrees of freedom; and sig � statistical significance.
Cardiology Research and Practice 5

Table 5: Median values of the parameters involved in the performance of the radial punction (interquartile ranges).
Parameters Radial calcinosis No radial calcinosis p value
Time to find artery (minutes) 3 (2, 10) 2 (1, 5) 0.01
Number of attempts 2 (1, 3) 2 (1, 2) 0.09
Access time (minutes) 37 (20, 60) 35 (20, 50) 0.16
Artery occlusion
Absent 73 97
0.4
Present 4 2
Between the two groups, artery lumen patency at 48 h follow-up, documented by RUS examination, showed a numerically higher occlusion rate in the RC
group, which was not statistically significant (5.19% vs. 2.02%, p � 0.4).

hypertensives, and chronic kidney disease patients, with a uncalcified tissue [16]. Indeed, unstable lesions are associ-
strong emphasis on smoking (4.8 times higher risk). ated with focal calcium deposits that may be related to fi-
Our findings are clinically important for several other brous cap disruption [15]. Calcium in a spotty distribution
reasons. First, RUS may serve as a pre- and peri-procedural has previously been observed, pathologically, in sudden
adjuvant tool for the interventionist, facilitating a “per coronary death victims [17]. While spotty calcification was
primam” selection of coronary calcium debulking technique, more commonly associated with unstable plaques, extensive
intuiting stent underexpansion, and preparing the inter- calcification was more common with stable plaques [17].
ventionist to expect a more difficult sheath placement or The medial layer of the vessel wall is composed of
even radial access failure, with a longer, more complex smooth muscle cells and elastin-rich extracellular matrix.
procedure. Not losing the radial access advantages in Calcification of the media occurs preferentially along the
complex PCIs of severe calcific disease is of paramount elastic lamina, as opposed to the diffuse localization seen in
importance [14]. Second, RUS may be useful to cardio- intimal calcification, and is associated with diabetes, kidney
vascular surgeons, since the radial artery is commonly used disease, hypertension, and osteoporosis (also referred to as
as a conduit for coronary artery bypass and the presence of Monckeberg’s sclerosis). The result of medial calcification is
calcifications may reduce suitability of this graft. Third, the a stiffening of the artery wall, with an associated rise in blood
strong relationship we found between RC and severity of pressure, and a higher risk of cardiovascular mortality than
coronary artery disease and stenosis not only serves to that of intimal artery calcification, because left ventricular
predict the presence of severe disease, but also aids in the strain, hypertrophy, and decreased myocardial perfusion
identification of patients demonstrating established arterial during diastole appear as maladaptive mechanisms
disease who need intensive risk factors control and follow- [16, 18, 19].
up management. At the same time, both layers can be affected simulta-
For many decades, vascular calcification has been noted neously, with exponential harmful effect [20]. RUS can
as a consequence of aging. Studies now confirm that vascular detect both forms of vascular calcification, as illustrated in
calcification is an actively regulated process and shares many Figure 2. Forearm fluoroscopy can also very obviously detect
features with bone development and metabolism. It occurs mediocalcinosis. An illustrative example is Figure 4, which
in two sites, the tunica intima and the tunica media, with shows how pregnant mediocalcinosis is and how distinctly it
different disease association and outcomes (Figure 3). can be seen on a forearm X-ray. Such diffuse changes are
The intimal layer of the vessel wall is normally composed most common in end-stage kidney disease. Our center is a
of endothelial cells and a small amount of subendothelial dedicated ultrasound-assisted distal radial access center,
connective tissue. In atherosclerosis, the intima becomes having switched to this approach since 2019 [10–12]. Duplex
greatly inflamed and thickened and calcification occurs. US was used in the operating room to investigate all forearm
Natural history is that microcalcifications may arise inside arteries. RA diameter and peak systolic velocity were
lipid pool following the apoptosis of smooth muscle cells or measured at the wrist level. We believe the use of ultrasound
macrophages. They coalesce into larger mases over time to guidance enables the operator to identify important ana-
form speckles, further progressing to calcified sheets or tomical landmarks and avoid injuring adjacent structures.
plates. Fragmentation of these sheets leads to nodules that US can be also used to determine whether the lumen is large
may extend to the lumen and become protuberant with enough to accommodate the necessary sheath and check for
discontinuation of the endothelium [15]. Calcification of calcifications that can block the equipment delivery.
coronary arteries is an excellent predictor of atherosclerotic Therefore the RC aspect is also relevant for the operator’s
plaque burden and may contribute to atherosclerotic plaque success as it can affect performance index. In our study, time
rupture, though the connection between atherosclerotic of puncture and the number of attempts were similar across
plaque calcification plaque rupture is heavily debated. the two groups, but the total time to find the artery by US as
Several studies show a link between high CAC and risk of well as the artery occlusion rate was higher in the radial
cardiac events and mortality, yet some studies have sug- calcification population (Table 5).
gested that the most calcified plaques may be more stable, Vascular ultrasound-based imaging techniques allow
and that the plaques most vulnerable to rupture may be relatively inexpensive and nonevasive widely available
those which have a mixed composition of calcified and means to detect VC and to differentiate between
6 Cardiology Research and Practice

Vascular calcification

Medial Intimal

Diabetes
Renal Disease Atherosclerosis
Ageing

CAC score

Plaque
Stiffness rupture
Poor Cardiac Perfusion
Arrhythmias Myocardial Infarction
Heart Failure

Figure 3: Site-specific phenotype of calcific lesions according to their location within the arterial wall.

interventions is increased when subclinical athero-

sclerosis is detected.
(2) Although obtained in a small sample, these results
indicate the usefulness of radial ultrasound as a
further screening tool to identify patients who de-
serve consideration for a coronary noninvasive test.
It is important to note, however, that this study was
performed in patients who had undergone cardiac
catheterization because of suspected or proved heart
diseases; thus, whether our results can be extended to
patients without a cardiovascular history remains to
be defined.
(3) Significant ischemic coronary disease was defined by
Figure 4: Forearm radiography: diffuse mediocalcinosis along the the decision to continue with/history of PCI or/and
entire length of the radial artery (arrow). CABG. Although coronary revascularization is a
medical decision based on proven myocardial is-
Mönckeberg’s medial calcific sclerosis and the atheroscle- chemia, not all significant coronary stenoses are
rosis-related lesions and assess arterial wall abnormalities, followed by correct treatment and some nonsignif-
such as intima-medial wall thickening and endothelial icant coronary stenoses are overtreated.
dysfunction [21]. This has been well described within pe- (4) It should be emphasized that the calcification scoring
ripheral arterial disease, predominantly chronic limb and evaluation is operator dependent, therefore
threatening ischemia [22] and carotid atherosclerosis [23] subjective; however, we have adopted a policy of not
where US is a valuable tool for disease and risk assessment, exploring arteries that appear “borderline” or poor-
indicated by the guidelines. Our findings are in line with the quality images, projections, and so on; only clear
consistent evidence that VCs affects the entire arterial tree, calcific disease was counted as positive. Coronary
adding another vessel to the puzzle and draws attention angiography has low-moderate sensitivity compared
upon careful radial artery evaluation, especially when US is to IVUS and CT for detection of CAC but is very
performed before and during cannulation anyhow. specific (high positive predictive value) [24, 25].
(5) Another limitation of the current study is the lack of
histologic data to correlate with duplex findings.
4.1. Study Limitations
Histologic data would be helpful because the precise
(1) Although detecting subclinical atherosclerosis is level of calcifications within the vascular wall cannot
valuable in risk stratification, we must acknowledge be determined by the imaging technique used, and
that direct proof that such detection translates into a the underlying pathology (atherosclerosis vs. Mon-
better outcome is lacking, although several reports ckeberg’s sclerosis), therefore, cannot be determined
suggest that the frequency of use of risk-modifying either.
Cardiology Research and Practice 7

5. Conclusion secondary events in patients with coronary artery disease,”

Atherosclerosis, vol. 256, pp. 29–34, 2017.
RC may be associated with calcific coronary plaques fre- [7] F. Jashari, P. Ibrahimi, R. Nicoll, G. Bajraktari, P. Wester, and
quently. These findings highlight the potential beneficial M. Y. Henein, “Coronary and carotid atherosclerosis: simi-
examination of radial arteries whenever CAD is suspected. larities and differences,” Atherosclerosis, vol. 227, no. 2, 2013.
[8] G. Sirimarco, P. Amarenco, J. Labreuche et al., “Carotid
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RC: Radial calcification [9] J. S. K. Chan, A. M. A. Shafi, C. Grafton-Clarke, S. Singh, and
RUS: Radial ultrasound A. Harky, “Concomitant severe carotid and coronary artery
CAG: Coronary artery angiography diseases: a separate management or concomitant approach,”
CAD: Coronary artery disease Journal of Cardiac Surgery, vol. 34, no. 9, pp. 803–813, 2019.
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MI: Myocardial infarction access for coronary and peripheral procedures: a multicenter
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Heart Journal, vol. 42, pp. 3227–3337, 2021.
The authors report no financial relationships or conflicts of [14] A. Achim, M. Marc, and Z. Ruzsa, “Surgical turned-downed
interest regarding the content herein. Current study received CHIP cases-can PCI save the day?” Frontiers in Cardiovas-
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Conflicts of Interest into the unstable features of the coronary atherosclerotic
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The authors declare that they have no conflicts of interest Journal of Clinical Investigation, vol. 52, Article ID e13671,
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