Eur J Vasc Endovasc Surg 30, 476–488 (2005)
`doi:10.1016/j.ejvs.2005.04.030, available online at http://www.sciencedirect.com on
`
`REVIEW
`
`Aortic Calcification
`
`R.W. Jayalath, S.H. Mangan and J. Golledge*
`
`Vascular Biology Unit, Department of Surgery, School of Medicine, James Cook University, Townsville,
`Qld 4811, Australia
`
`Objectives. Vascular calcification is a complicating factor observed in advanced atherosclerosis. This review summarises the
`present knowledge regarding abdominal aortic calcification.
`Design. Literature review.
`Methods. A literature review was carried using MEDLINE and PUBMED with the search terms ‘abdominal’, ‘aortic’ and
`‘calcification’. Articles were assessed for data regarding mechanisms, measurement, risk factors and outcomes of aortic
`calcification.
`Results. Thirty relevant studies were identified. These demonstrated a positive correlation between abdominal aortic
`calcification and the following factors: older age, hypertension, and smoking. Further studies are required to critically assess
`other risk factors such as gender, diabetes mellitus and renal failure. Calcification of the abdominal aorta is associated with an
`increased risk of mortality, coronary heart disease and stroke.
`Conclusion. Aortic calcification predicts an increased incidence of cardiovascular events, however, the reasons for this
`association requires further investigation. Accurate measurement of aortic calcification is likely to be increasingly used to
`determine the risk of cardiovascular events.
`
`Keywords: Vascular calcification; Aortic; Patient outcomes.
`
`There is great interest in vascular calcification in terms
`of risk factors and subsequent outcomes. Studies in the
`coronary arteries demonstrate an association between
`calcification and cardiovascular events, in particular
`myocardial infarction.1 For example, a meta-analysis
`by O’Malley et al.2 demonstrated that coronary artery
`calcification was associated with a 8.7 fold increased
`risk of cardiac events and 4.2 fold increased risk of
`death or myocardial infarction. Other studies examin-
`ing the coronary circulation demonstrate a correlation
`between the degree of calcification and the severity of
`atherosclerosis and clinical events.3–10 Similar relation-
`ships between calcification and cardiovascular events
`have been demonstrated in other vascular beds, such
`as the aortic arch11–13 and the thoracic aorta.14–16
`Whether the calcification has a direct detrimental effect
`or is simply a marker of atherosclerotic burden is
`unknown.
`
`*Corresponding author. Assoc Prof Jonathan Golledge, Director,
`Vascular Biology Unit, Department of Surgery,
`James Cook
`University, Townsville, Qld 4811, Australia.
`E-mail address: jonathan.golledge@jcu.edu.au
`
`Unlike the coronary circulation, relatively little is
`understood about
`the importance of calcification
`within the abdominal aorta. Similar to the coronary
`circulation, aortic calcification likely influences sub-
`sequent cardiovascular events such as aortic occlusion,
`aneurysm development and distal embolisation.17,18
`Calcification within the aorta also impacts on medical
`and surgical treatment for example by impairing the
`outcome of aortic stenting and aneurysmal repair.18 To
`better understand the significance of abdominal aortic
`calcification, this review will focus on the measure-
`ment, risk factors and outcomes of abdominal aortic
`calcification.
`To appreciate the significance of abdominal aortic
`calcification, an understanding of the mechanism of
`vascular calcification is required. Seminal work car-
`ried out by Virchow and Rokitansky in the 19th
`century showed that fully formed bone tissue was
`present in atherosclerotic arteries.19,20 However, it is
`now recognised that vascular calcification involves a
`complex, regulated process of biomineralisation.21,5
`Although the precise mechanism of vascular
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`Abdominal Aortic Calcification
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`477
`
`calcification is yet to be elucidated, it most likely
`involves some elements of bone metabolism.4,22
`Broadly, two theories have been suggested, the active
`model which incorporates analogous cell types and
`cytokines to those involved in bone remodelling and
`the passive physiochemical model. Currently, most
`support is for the active model (see review by Doherty
`et al.22).
`An understanding of the histopathology of vascular
`calcification is necessary to appreciate its detection by
`imaging modalities. Vascular calcification is classified
`as intimal and medial, according to the arterial layer in
`which the calcification occurs.4,6,23,24 Both types are
`observed in the abdominal aorta.4,21 Most studies to
`date have concentrated on intimal calcification due to
`its association with atherosclerosis. Medial calcifica-
`tion or Monckeberg sclerosis occurs independently of
`atherosclerosis.22,23,25 This form of calcification is
`commonly found in patients with renal failure and
`diabetes mellitus and has, therefore, been suggested to
`occur as a result of a disturbance in metabolic,
`electrolyte and pH balance.22,26 It is thought that this
`form of calcification has a predilection for arteries less
`prone to atherosclerosis. Medial calcification is rarely
`seen in the coronary arteries but does affect the
`abdominal aorta.4,22 There is often a lack of differen-
`tiation between the two types in the literature, likely as
`a result of the limitation of imaging modalities to
`differentiate the two, which requires histopathology.
`
`Methods
`
`Study identification
`
`To identify appropriate studies, a search was per-
`formed using the MEDLINE and PUBMED database.
`The search included the primary descriptors abdomi-
`nal, aortic and calcification. The search was limited to
`articles in English. One hundred and seventy-eight
`suggestive articles were located and the correspond-
`ing abstracts were read to identify those that were
`appropriate. The reference lists of these articles were
`used to identify additional articles missed by the
`computerised database search.
`
`Inclusion and exclusion criteria
`
`To be included in this review, the study had to provide
`data in relation to the method of measurement,
`quantification,
`the associated risk factors or the
`outcome of abdominal aortic calcification. Studies
`published prior to 1984 were excluded from the
`
`review. From the initial, 178 articles identified from
`the MEDLINE/PUBMED searches, a total of 30 papers
`were accepted as providing relevant data.3,16,27–54
`
`Measurement of Aortic Calcification
`
`The measurement of arterial calcification may become
`a significant tool to predict clinical events associated
`with the abdominal aorta. Three imaging methods
`have been employed to detect, quantify and define
`calcification (Table 13,16,27–54). These include electron
`beam computed tomography (EBCT), computed tom-
`ography (CT) and plain X-ray. Presently no modality
`has been accepted as the gold standard for the
`measurement of abdominal aortic calcification, conse-
`quently there is little assessment of the sensitivity and
`specificity of these techniques.
`
`Electron beam computed tomography (EBCT)
`
`EBCT is a non-invasive method of detecting calcifica-
`tion and is increasingly used to assess coronary
`arteries.2,55,56 The advantages of EBCT is that it allows
`very rapid acquisition of images, preventing image
`blurring and accurate visualisation of small calcific
`deposits in the coronary arteries without utilising
`contrast media.57,58 Within the coronary circulation
`EBCT detection of calcification has been shown to
`correlate with the angiographic severity of coronary
`artery disease (CAD).57,58 The Expert Consensus
`Document of the American College of Cardiology/
`American Heart Association states that the sensitivity
`and specificity of EBCT to detect coronary artery
`stenosis or occlusion demonstrated on angiography is
`90.5 and 49.2% in their evaluation of 3683 patients
`enrolled in 16 studies.59
`Four studies using EBCT to quantify abdominal
`aortic calcification were identified.3,16,27,28 Each inves-
`tigator used a different scoring system to quantify the
`severity of aortic calcification and examined different
`sites within the aorta. The scoring method in these
`studies is similar to that employed in the coronary
`circulation, but varies between investigators. For
`example, Allison et al.28 utilised a modification of the
`Agatston method whereas, Reaven and Sacks27 uti-
`lised a calcium score based on the sum of individual
`lesions along the scanned section of the aorta. These
`studies did not report the reproducibility of their
`method of analysis, however, Kuller et al.3 in their 11-
`year prospective study reported high reproducibility
`with an inter-class correlation of 0.98.
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`R. W. Jayalath et al.
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`Table 1. Studies measuring abdominal aortic calcification
`
`References Modality
`
`Subjects
`
`Quantification of calcification
`
`Region assessed
`
`[3]
`[16]
`[27]
`[28]
`[29]
`[30]
`[31]
`[32]
`[33]
`[34]
`[35]
`[43]
`[48]
`[49]
`[50]
`[51]
`[36]
`[37]
`[38]
`[39]
`[40]
`[41]
`[42]
`[44]
`[45]
`[46]
`[47]
`[52]
`[53]
`[54]
`
`EBCT
`EBCT
`EBCT
`EBCT
`CT
`CT
`CT
`CT
`CT
`CT
`CT
`CT
`CT
`CT
`CT
`CT
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`X-ray
`
`169
`99
`245
`650
`129
`40
`137
`116
`20
`405
`257
`29
`26
`152
`102
`36
`89
`79
`2151
`97
`554
`720
`177
`758
`773
`110
`182
`2467
`2515
`6913
`
`Calcium score
`Calcium score
`Calcium score
`Calcium score
`Calcification grade
`Calcification volume
`Aortic calcification area index (%)
`Aortic calcification volume (%)
`Atherosclerosis index
`Degree of calcification (%)
`Calcification grades
`Calcification volume (%)
`Aortic calcification index
`Vessel wall or thrombus calcification
`Aortic calcification index
`Aortic calcification index
`Calcification grades
`Calcification grades
`Calcification grades
`Calcific deposit length (mm)
`AAC index
`Aortic length involved
`Calcification grades
`Calcification grade
`Calcium score
`Semi-quantitative score
`Presence of calcium
`Calcium score
`Calcium score
`Calcium score
`
`Aortic arch to iliac bifurcation
`Abdominal aorta
`Abdominal aorta (right kidney to iliac bifurcation)
`Diaphragm to iliac bifurcation
`Coeliac artery origin; left renal vein level; aortic bifurcation
`SMA to iliac bifurcation
`Above common iliac bifurcation
`Above common iliac bifurcation
`Abdominal aorta (L3 or L4)
`Aortic arch to bifurcation
`SMA to bifurcation
`At and above common iliac bifurcation
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta (T12–S1)
`Aortic wall at each vertebral segment (L1–L4)
`Abdominal aorta (L1–L5)
`Abdominal aorta (L1–L4)
`Abdominal aorta (T12–S1)
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta
`Abdominal aorta (L1–L4)
`
`AAC, abdominal aortic calcification; L, lumbar vertebrae; SMA, superior mesenteric artery; T, thoracic vertebrae; S, Sacrum.
`
`Computed tomography (CT)
`
`Twelve studies have used CT to measure abdominal
`aortic calcification,29–35,43,48–51 however, there is vari-
`ation in the grading and location of these measure-
`ments. For example, Kimura et al.31 quantified the
`aortic calcification as a percentage of
`the cross
`sectional area of the aorta whereas, Miwa et al.32
`although using a similar quantification method,
`expressed the calcification as a percentage of the aortic
`volume in their prospective study. A retrospective
`study graded the calcification as a percentage of the
`aortic circumference.29 Most
`investigators did not
`comment on the reproducibility of their measurement
`method, however, Miwa et al.32 reported an intra-
`observer and inter-observer coefficient of variation of
`4.4 and 5.1%, respectively.
`
`X-ray
`
`The simplest method of detecting abdominal aortic
`calcification is with plain abdominal X-ray. Quantifi-
`cation using this technique, however, is highly varied,
`with a number of grading systems being reported. Our
`
`Eur J Vasc Endovasc Surg Vol 30, 11 2005
`
`review identified 14 studies which utilised X-ray to
`measure abdominal aortic calcification.36–42,44–47,52–54
`In a study by Kawaguchi et al.,36 grade 1 was
`equivalent to no calcification, grade 2 described patchy
`calcification and grade 3 denoted calcification along
`the entire abdominal aorta giving it a lead pipe shape
`on X-ray. Jie et al.,37 however, specified grade 0 as
`having no calcification and grade 4 as having the aorta
`outlined with calcification. In the study by O’Donnell
`et al.38 the calcification grade was dependent on the
`longitudinal
`length of aortic wall affected. Scores
`ranged from grade 0, which had no calcific deposits
`to grade 3 that had two thirds or more of the
`longitudinal wall calcified. The accuracy and reprodu-
`cibility of the techniques employed were discussed in
`many of the studies,38,40–42,44–47,52,53 although not
`rigorously. However, four studies failed to discuss
`this issue.36,37,39,54 For example, Hak et al.41 required
`two independent observers to examine the films and
`be in consensus regarding their reading.41 The
`investigators reported a percentage of agreement for
`absence versus presence of progression of calcification
`of 88% with a k statistic of 0.74. Nakamura et al.39 on
`the other hand measured the length of abdominal
`aortic calcification by tracing the regions onto tracing
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`Abdominal Aortic Calcification
`
`479
`
`paper. Although an electronic calliper with a resol-
`ution of 0.01 mm was used, the author did not report
`the reproducibility or accuracy of this method.39
`
`Abdominal aortic region assessed
`
`The region of the abdominal aorta in which calcifica-
`tion is quantified is likely to have a significant impact
`on the score achieved. In general, atherosclerosis and,
`therefore, calcification is more common at arterial
`bifurcations.60 Some studies failed to specify the
`regions of the abdominal aorta that were analysed.34,
`36,42,45,46,48,50,51 In studies that did specify the region
`investigated, there was marked variation in the site
`examined. For example, Kimura et al.31 assessed the
`calcification just above the bifurcation of the common
`iliac arteries, while Reaven and Sacks27 scanned from
`the kidney to the iliac bifurcation.
`
`Clinical Determinants of Abdominal Aortic
`Calcification
`
`The incidence and severity of abdominal aortic
`calcification was studied in relation to a variety of
`risk factors in the articles reviewed.3,27–29,31,32,34,35,38,40–
`43,47,48,50,51 The heterogeneity in the studies identified
`hampers the synthesis of results in a systematic
`manner. This heterogeneity arises from the variation
`in study design and outcome measures used to report
`findings.
`A number of sources contribute to the variability in
`study design. Firstly, retrospective, prospective and
`cross sectional studies were included in the review.
`Secondly,
`the cohorts under investigation varied
`between the studies. For example, Kuller et al.3 had a
`cohort of women going through menopause, while
`Kiel et al.40 looked at the Framingham Heart Study
`population. Thirdly,
`there was variability in the
`detection and quantification of aortic calcification
`(Table 1). The imaging modalities used and the
`sections of
`the abdominal aorta studied varied
`between the studies. The quantification of calcification
`also varied, with subjective and objective measure-
`ments carried out. Fourthly, a majority of studies
`considered more than one clinical determinant in
`assessing for a relationship to abdominal aortic
`calcification.
`The outcome measures used to report findings also
`varied between studies. Measures used included
`relative risk (RR), odds ratio (OR), hazard ratio (HR)
`and correlation coefficients. A majority of studies also
`failed to publish unanalysed data. In the following
`
`section, we discuss the findings of these studies in
`relation to the different risk factors for abdominal
`aortic calcification. Due to the variation in presentation
`of data and outcome measures, it is not possible or
`useful to combine data from these studies. Instead we
`report the findings of the different studies in relation to
`there quality.3,27–29,31,32,34,35,38,40–43,47,48,50,51
`
`Age
`
`The atherosclerotic process begins during childhood
`and may progress to form an advanced atheroma with
`some lesions becoming calcified.28 Therefore, age
`would be expected to be an important determinant
`of the presence and severity of abdominal aortic
`calcification. Five studies examined the relationship
`of aortic calcification to age.27,28,32,38,40 The finding
`across all
`the studies is that abdominal aortic
`calcification is positively related to age. In two studies,
`it was possible to separate the cohort into older and
`younger participants with high and low calcification
`levels.27,32 The larger of these studies, conducted by
`Reaven and Sacks27 had 245 participants, with
`calcification measured using EBCT. This study
`revealed that elderly people (ageR61 years) had
`more severe aortic calcification.27
`The remaining three studies each contained a larger
`number of subjects but did not present their data in a
`manner enabling separation based on age or calcifica-
`tion severity.28,38,40 In the study by Allison et al.,28 the
`results on the prevalence and severity of abdominal
`aortic calcification were based on age specific groups.
`However, the authors failed to indicate how many
`patients were in each age specific group. The investi-
`gators demonstrated a very important influence of age
`on both prevalence and severity of aortic calcification
`in both genders (Fig. 1). For example, at age !50 years
`the prevalence of abdominal aortic calcification is 16
`and 20% in women and men, respectively. This
`increases to 93 and 98% by age O70 in women and
`men, respectively. The odds ratio (OR) for presence of
`abdominal aortic calcification per 10 years was 5.5 for
`women and 5.6 for men (95% CI, 3.4–9.0 and 3.6–8.8,
`respectively).28 While O’Donnell et al.38 in their much
`larger study also showed a correlation between age
`and aortic calcification; however, they utilised X-ray
`which is a less sensitive method to quantify calcifica-
`tion. Similarly Kiel et al.40 reported a six-fold and
`eight-fold increase in aortic calcification in men and
`women, respectively during a 25-year follow-up study.
`The literature search did not
`locate any studies
`showing a negative or nil correlation with age,
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`480
`
`R. W. Jayalath et al.
`
`Fig. 1. Prevalence (A) and severity (B) of abdominal aortic calcification with increasing age in men (black) and women (clear).
`(Adapted from Allison et al. with permission).28
`
`indicating age as an important risk factor for abdomi-
`nal aortic calcification.
`
`Gender
`
`Males have a higher risk of atherosclerosis compared
`to females, therefore, gender would be expected to be
`an important determinant of abdominal aortic calcifi-
`cation.61 In the coronary circulation, it is known that
`calcification is greater in men than in women.62 Six
`studies reported findings with respect to gender and
`its relationship to abdominal aortic calcification.3,28,35,
`38,40,41 Four of these studies had cohorts of both males
`and females28,35,38,40 and of these only Dixon et al.35
`presented data in a manner allowing separation into
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`
`high and low calcification levels. Dixon et al.35 found
`that significantly more females (20%) than males (5%)
`60–80 years had advanced calcification (p!0.05).
`However,
`they found no significant association
`between the presence of abdominal aortic calcification
`and gender.35
`The study by Allison et al.28 was cross sectional in
`nature and utilised EBCT. They demonstrated that the
`prevalence of calcification was greater in males, with
`70% of men and 47% of women less than 50 years and
`98% of men and 91% of women aged 60–70 years
`having measurable aortic calcification. The investi-
`gators also reported that the abdominal aorta was
`the commonest site of vascular calcification in
`women.28 While the study by Kiel et al.,40 which
`used a less sensitive imaging modality, examined
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`481
`
`aortic calcification in the Framingham Heart Study
`cohort of men and women over a 25-year period.40
`Calcification progressed at similar rates in both
`genders, but
`in women there was a significant
`correlation between bone loss and the rate of increase
`in aortic calcification.40
`Two studies examined abdominal aortic calcifica-
`tion in cohorts of women only.3,41 Kuller et al.3 and Hak
`et al.41 were both population based longitudinal
`studies looking at the impact of menopause on aortic
`calcification and bone loss in women. The higher
`powered of these two studies was conducted by Hak et
`al.41 In this study, 236 initially premenopausal women
`were followed for 9 years as well as a cross sectional
`study of 720 postmenopausal women.41 From the
`cohort of 236 women, 59 (25%) showed progressive
`aortic calcification during the follow-up period. The
`study also investigated bone loss using metacarpal
`radiometry to assess the metacarpal cortical area
`(MCA). The loss of bone mass was positively
`correlated with progression of aortic calcification.
`The mean loss of MCA in women with progressive
`aortic calcification and those without was 3.2G
`0.04 mm2 and 2.0G0.2 (pZ0.01), respectively.
`Although relatively few studies have investigated
`the relationship of gender to abdominal aortic calcifi-
`cation critically, there is evidence to suggest that a
`gender difference exists. Gender may also play a role
`in determining the distribution of vascular calcifica-
`tion. Larger prospective studies of both genders are
`required to assess this in a more critical manner.
`
`Diabetes mellitus
`
`Diabetes mellitus is associated with arterial calcifica-
`tion, both medial and atherosclerotic intimal types.61
`Six studies were identified which analysed the
`relationship of abdominal aortic calcification to dia-
`betes mellitus.27–29,34,38,42 Of these, two studies used
`diabetes mellitus as a single variable under investi-
`gation.27,42 The remaining studies analysed diabetes
`mellitus as one of a number of clinical determinants
`considered.28,29,34,38 Five studies supported the
`relationship of aortic calcification to diabetes melli-
`tus.27,28,34,38,42
`Only one study compared abdominal aortic calci-
`fication in diabetics and non-diabetics.42 Niskanen et
`al.42 identified aortic calcification in 29% of diabetics
`and 17% of non-diabetic men (pZ0.05) and 26% of
`diabetic and 19% of non-diabetic women (pZ0.06) in a
`5-year follow-up study. Although the investigators
`originally quantified the calcification into four cat-
`egories, the final data is presented as the total number
`
`of patients with any calcification. Therefore, no
`differentiation is made in terms of the severity of
`aortic calcification. Reaven and Sacks27 also assessed
`the impact of diabetes on abdominal aortic calcifica-
`tion using EBCT. They found that aortic calcification
`was positively related to the duration of diabetes (rZ
`0.23, p!0.01).27
`Four studies investigated the impact of diabetes
`mellitus as one of a number of clinical determinants
`under investigation.28,29,34,38 However, diabetics have
`a higher incidence of other traditional cardiovascular
`risk factors, such as hypertension and hyperlipidae-
`mia,34,38 which may confound the analysis of the
`relationship between diabetes mellitus and abdominal
`aortic calcification. The limited studies carried out to
`date suggest that abdominal aortic calcification is more
`common in diabetics.28,34,38 In contrast, Matsushita et
`al.,29 in their assessment of a male cohort did not find a
`correlation between diabetes and the incidence or
`severity of calcification. However, this retrospective
`study contained the smallest cohort of subjects
`compared to the other studies.
`
`Hypertension
`
`Hypertension is a known risk factor for atherosclero-
`sis.17,63 Aortic calcification changes the normal vascu-
`lar hemodynamics by increasing arterial rigidity.39,46,64
`Given that peripheral arterial calcification will affect
`the measurement of blood pressure,39 any demon-
`stration of an association between blood pressure and
`prevalence of aortic calcification does not necessarily
`imply a causal relationship.
`Seven studies examined the relationship of abdomi-
`nal aortic calcification and hypertension.3,28,29,31,32,38,43
`Two studies allowed comparison between hyperten-
`sive and non-hypertensive subjects, based on the
`severity of calcification.29,31 The data from both these
`studies indicate that hypertensive subjects have more
`severe abdominal aortic calcification.29,31 Kimura et
`al.31 showed that in patients on haemodialysis there is
`also an association between abdominal aortic calcifica-
`tion and high systolic blood pressure. While Matsush-
`ita et al.29 in their retrospective study of 129 males with
`abdominal aortic aneurysms (AAA), showed that
`calcification was more common with hypertension
`(at the level of the coeliac artery p!0.05 and at the
`level of left renal vein p!0.0005).
`Four studies did not present data in a manner
`allowing comparison between hypertensive and non-
`hypertensive patients.3,28,32,38,43 However, several
`important associations were revealed by these studies.
`For example, Allison et al.28 demonstrated an
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`
`R. W. Jayalath et al.
`
`association between hypertension and distal aortic
`calcification using multi-variable logistic regression in
`a highly powered study using EBCT. In men the OR
`was 2.1 (95% CI 0.9–4.8), while in women OR was 2.6
`(95% CI 1.1–6.2).28 While O’Donnell et al.34 also
`reported an association between systolic blood press-
`ure and aortic calcification (rZ0.27, p!0.0001). This
`study, although containing the largest number of
`subjects, utilised X-ray, a less sensitive imaging
`modality to quantify calcification. In contrast to the
`above findings, a prospective open labelled study by
`Arai et al.43 did not detect a correlation between aortic
`calcification and systolic or diastolic blood pressure.
`However, this study only included 29 subjects.
`Thus, the available studies suggest an association
`between hypertension and abdominal aortic calcifica-
`tion. Whether hypertension predisposes to aortic
`calcification or patients with vascular calcification
`have higher blood pressure readings remains to be
`determined.
`
`Smoking
`
`Cigarette smoking is a recognised risk factor for
`cardiovascular disease and atherosclerosis.44,53,65 In
`an autopsy study carried out by Auerbach and
`Garfinkel,66 a direct relationship between the athero-
`sclerotic lesions, recorded as calcification, and smok-
`ing habits of male patients was observed. More
`extensive alterations were found in the abdominal
`aorta than in the thoracic portion and the extent of the
`lesions increased with the number of cigarettes
`smoked.66 Five studies have looked at the effect of
`cigarette smoking on abdominal aortic calcification
`using imaging modalities.27–29,38,44 Of these, only one
`looked at cigarette smoking as a single variable under
`investigation.44 Witteman et al.44 used plain X-ray to
`examine the relationship between smoking and aortic
`calcification in women in a population based 9-year
`follow-up study. Compared to those who had never
`smoked, the relative risk (RR) of those who smoked
`1–9 cigarettes per day was 1.4 (95% CI 1.0–2.0), 10–19
`cigarettes per day was 2.0 (95% CI 1.6–2.5) and O20
`cigarettes per day was 2.3 (95% CI 1.8–3.0) after
`adjustment for age and other cardiovascular risk
`factors.44 Smoking cessation over time resulted in a
`reduction in the RR for vascular calcification, however,
`significant excess risk was observed 5–10 years after
`quitting (RR 1.6; 95% CI 1.1–2.2).44
`The remaining studies examined the effect of
`cigarette smoking on abdominal aortic calcification
`as one of a number of clinical determinants con-
`sidered.27–29,38 A majority of these studies showed
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`Eur J Vasc Endovasc Surg Vol 30, 11 2005
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`strong evidence to support smoking as a risk factor for
`aortic calcification.27,28,38 These studies all had large
`cohorts and those by Reaven and Sacks27 and Allison
`et al.28 also utilised EBCT. Although there is strong
`evidence to support smoking as risk factor for aortic
`calcification, Matsushita et al.29 failed to report any
`correlation at the aortic bifurcation. However, this was
`the smallest study, with retrospective analysis of 129
`subjects and subjective quantification of calcification.
`
`Renal failure
`
`Patients on dialysis have an incidence of cardiovas-
`cular events 10–30 times greater than those of the
`general population.67 This high incidence of vascular
`calcification seen in patients with chronic renal failure
`(CRF), however, cannot simply be explained by the
`prevalence of atherosclerosis in this patient group. It
`appears likely that metabolic parameters such as
`hyperphosphataemia and elevated calcium–phos-
`phorus product also plays an important role in the
`excess incidence of vascular calcification in this patient
`group.68 Despite the convincing evidence that renal
`failure is a risk factor for vascular calcification, there
`are no studies comparing abdominal aortic calcifica-
`tion in patients with or without renal failure. However,
`four studies have examined the risk factors for
`abdominal aortic calcification in subgroups of patients
`with CRF.31,36,47,48 These studies have demonstrated
`that aortic calcification is more common in patients
`who are on dialysis for longer periods, both peritoneal
`and haemodialysis.31,36 For example, Kawaguchi et
`al.36 found that the mean duration on dialysis of
`patients with grade 1 abdominal calcification was 41
`months, while for patients with grade 3 calcification it
`was 68 months (p!0.001). The larger study by Kimura
`et al.31, with a cohort of 137 haemodialysis patients,
`also supports this finding. They found that abdominal
`aortic calcification was greater with increased duration
`on dialysis (p!0.01).
`The mechanisms underlying aortic calcification in
`patients with CRF are not completely understood. In
`addition to predilection for atherosclerosis and meta-
`bolic derangement, patients with CRF are commonly
`treated with calcium containing phosphate binders.
`Evidence from both animal and human studies
`indicate that this medication promotes aortic calcifica-
`tion.65,68 In a rat model of renal failure, calcium
`containing phosphate binders promoted aortic calcifi-
`cation.68 Similarly in a randomised controlled trial,
`calcium containing phosphate binders promoted
`aortic calcification.65 However, the currently available
`human studies investigating the relationship of renal
`
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`Abdominal Aortic Calcification
`
`483
`
`failure to aortic calcification consist of small cohorts;
`thus firm conclusions are difficult to reach. Further
`studies with larger patient numbers are required to
`examine this issue more thoroughly.
`
`Peripheral arterial disease (PAD)
`
`Aortic calcification is a common finding in patients
`with symptomatic peripheral vascular disease and
`abdominal aortic aneurysm (AAA). Presently, there
`are relatively few studies that have investigated the
`relationship between abdominal aortic calcification
`and either of these two pathologies. In a study of 336
`post-mortem specimens of the aorta, aortic calcifica-
`tion was reported to be more prevalent and more
`severe in patients with previous symptoms of inter-
`mittent claudication.69 Two studies investigated the
`relationship between abdominal aortic calcification
`and peripheral arterial disease.42,49 However, both
`studies consisted of small subject numbers,
`thus
`limiting the information that can be gained. Niskanen
`et al.42 assessed a group of diabetics (type 2) and a
`control group over 5 years for aortic calcification using
`X-ray imaging. The prevalence of abdominal aortic
`calcification was higher in the subjects who developed
`intermittent claudication during follow-up than in
`those who were symptom free during the 5-year
`examination.42 Torres et al.49 demonstrated aortic
`calcification in all 145 patients with AAAs assessed
`by CT. The high prevalence of aortic calcification in
`patients with aneurysms simply may relate to the
`other risk factors for calcification in these patients.
`Further work is required to define the relationship
`between aortic calcification, aneurysm and occlusive
`disease.
`
`Serum calcification markers
`
`There are a number of lipids and proteins that have
`been identified as being important to the atherosclero-
`tic and calcific process. Some of these mediators are
`present in measurable levels within the serum. The
`ability to identify patients at risk of or who already
`have aortic calcification using serum markers could
`prove to be an invaluable