Coronary artery disease (CAD) is the leading cause of death in the world and is predicted to remain so for the next years. Noninvasive measures for evaluation of the atherosclerosis have emerged as adjuncts to traditional cardiovascular disease risk factors in an attempt to refine risk stratification and the need for more aggressive preventive strategies [13]. Different screening methods have emerged for this purpose, including stress ECG, stress echocardiography, and myocardial scintigraphy as well as the coronary calcium score using the MSCT.
To the best of our knowledge, we are the first to investigate the correlation between lower limb calcification using non-contrast CT and coronary artery disease severity through gold standard coronary angiography using Gensini score in ischemic heart disease patients.
Association of lower limb arterial calcification with coronary artery disease
In our study, there was borderline significant association between coronary artery disease (Gensini score) and each of total lower limb and aorto-iliac calcification. On the other hand, there was no significant association with each of femoro-popliteal and infra-popliteal calcifications.
Moreover, our study demonstrated that there was a significant association between the number of diseased coronaries and lower limb arterial calcification.
These results were compatible with results of many researchers as Shin et al. [14], Ouwendijk et al. [15], Reaven et al. [16], Criqui et al. [17], and Kim et al. [18].
Shin et al. [14] studied cardiac and peripheral arterial calcification by computed tomography in 103 PAD patients. The patients were categorized as non-significant CAD, single CAD, or multivessel CAD. He found that PAD patients with multivessel CAD had significantly higher peripheral arterial calcifications than those with non-significant CAD (p < 0.001).
Ouwendijk et al. [15] studied the association between vessel wall calcification (in aorto-iliac, femero-popliteal, and infra-popliteal vessels) by CT angiography and history of cardiac disease (including chest pain, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, and myocardial infarction) in 145 patients and found that cardiac disease was independently predictive for the presence of vessel wall calcifications (p = .05).
Reaven et al. [16] studied coronary artery disease and abdominal aorta calcification by electron beam computed tomography in 309 patients and showed that subjects with coronary artery or abdominal aorta calcification had a strikingly higher prevalence of coronary artery disease and all combined cardiovascular disease.
Criqui et al. [17] studied abdominal aortic calcifications (AAC) and coronary artery calcification (CAC) by computed tomography in 1974 patients and found that AAC and CAC predicted coronary artery disease and cardiovascular events independent of one another. Only AAC was independently related to cardiovascular mortality, and AAC showed a stronger association than CAC with total mortality (p = .01).
Kim et al. [18] studied coronary artery calcification (CAC), aortic calcification (AC), and obstructive coronary artery disease (OCAD) by computed tomography in 120 stable OCAD (luminal narrowing ≥ 50%) patients and 120 controls without OCAD and found that the prevalence of AC and CAC was significantly higher in OCAD patients than in controls (64% vs. 48%, p = 0.019; 57% vs. 32%, p < 0.001, respectively).
Tatsunori and Nemoto [19] investigated 197 patients with PAD who underwent coronary angiography and lower extremity computed tomography angiography; they calculated syntax score from coronary angiography while the lower limb artery calcification was expressed as calcium score in similar methods to Agatston score. They found that lower limb arterial calcification was a stronger predictor for cardiovascular death rather than syntax score among patients with peripheral artery disease.
And finally, Xiaoteng et al. [20] investigated the correlation of the extent of aortic arch calcification detectable on chest X-rays with the severity of coronary artery disease in patients with acute coronary syndrome in 1418 patients, and they found that the extent of aortic arch calcification detectable on chest X-rays might provide valuable information in predicting coronary artery disease severity in acute coronary syndrome patients.
Association of lower limb arterial calcification with coronary artery calcification
In our study, the lower limbs arterial calcification (total and segmental) was significantly associated with the coronary artery calcification.
These results were agreed with results of Shin et al. [14], Costacou et al. [11], Patsch et al. [21], Churchill et al. [22], and Takasu et al. [23].
Shin et al. [14] evaluated coronary and lower extremity arterial calcification (LEAC) by computed tomography in 103 PAD patients. Patients were categorized as non-significant CAD, single CAD, or multivessel CAD. He found that LEAC significantly correlated with CCS (r = 0.831, p < 0.001).
Costacou et al. [11] studied computed tomography of lower extremity and coronary artery calcifications in 121 patients and showed that lower extremities arterial calcification and the heart share many of the same risk factors; lower extremity arterial calcification is an independent correlate of the later presence of coronary artery calcification.
Patsch et al. [21] studied lower leg and coronary arterial calcifications by computed tomography in 46 patients and found that a significant positive correlation between lower leg arterial calcification and coronary artery calcification (r = 0.6; p < 0.01).
Churchill et al. [22] evaluate coronary artery and ascending and descending thoracic aorta calcifications by computed tomography in 1739 patients and found that ascending and descending thoracic aortic calcium have similar associations with traditional cardiovascular risk factors in diabetics and are independently associated with coronary artery calcium.
Takasu et al. [23] quantified coronary artery calcification (CAC) and descending thoracic aortic calcification (DTAC) by non-enhanced cardiac CT in 6814 patients aged 45–84 years old and concluded that DTAC was found to be a strong predictor of CAC independent of cardiovascular risk factors.
Association of coronary artery calcification with coronary artery disease
Quantification of the coronary artery calcification has been extensively studied for its ability to predict coronary artery disease.
Our study demonstrated that the coronary artery calcification was significantly associated with the coronary artery disease. In addition, there was a significant association between the number of diseased coronaries and total coronary artery calcifications.
These results were compatible with results of many researchers as Almasi et al. [24], Iwasaki and Matsumoto [25], Budoff et al. [26], Gokdeniz et al. [27], and Rosen et al. [3].
Almasi et al. [24] studied 202 consecutive patients who underwent conventional coronary angiography to assess the severity of coronary artery disease by Gensini score and computed tomography to measure CAC by Agatston algorithm and confirmed the strong relationship between the CAC and the presence and severity of stenosis in coronary arteries assessed by both the number of diseased vessels and also by the Gensini score.
Iwasaki and Matsumoto [25] studied coronary artery calcification (CAC) and significant coronary stenosis using coronary computed tomographic angiography (CCTA) in 651 patients and found that stepwise increased risk of coronary events associated with increasing CAC was caused by increasing incidence of significant stenosis.
Budoff et al. [26] evaluated coronary artery calcification by computed tomography and coronary artery disease by coronary angiography in 1851 patients. The overall sensitivity for CAC to predict obstructive disease on angiography was 95%, and the specificity was 66%. They also found that CAC provides incremental and independent power in predicting the severity and extent of significant CAD in symptomatic patients.
Gokdeniz et al. [27] studied coronary artery disease by Gensini score, and coronary calcium score (CAC) by computed tomography in 240 patients, found that Gensini score was significantly correlated with total CAC score.
Rosen et al. [3] studied coronary artery calcification and the severity of coronary disease by coronary angiography in 6814 subjects of The Multi-Ethnic Study of Atherosclerosis (MESA) and found that there is a significant relationship between the extent of calcification and mean degree of stenosis in individual coronary vessels; however, 16% of the coronary arteries showed significant stenoses without calcifications at baseline.
Analysis of risk factors of coronary artery and lower limb arterial calcification
In our study, we demonstrated that diabetes mellitus and hypertension were significantly associated with lower limb calcifications (total, aorto-iliac, and infra-popliteal). Lower limb arterial calcifications (total and segmental) were also positively correlated with increasing age. These results were compatible with results of Ouwendijk et al. [15], Allison et al. [28], and Chowdhury et al. [29].
Ouwendijk et al. [15] studied the association of vessel wall calcifications (in aorto-iliac, femero-popliteal, and below the knee) by CT angiography and cardiovascular risk factors in 145 patients and found that diabetes mellitus and age were independently predictive for the presence of vessel wall calcifications (all p = 0.05).
Allison et al. [28] studied 650 asymptomatic subjects referred to assess proximal and distal aorta and iliac vessels for atherosclerotic calcification and found that age and hypertension were the dominant risk factors for systemic calcified atherosclerosis.
Chowdhury et al. [29] studied 220 PAD patients that underwent CT to determine lower limb arterial calcification (LLAC) and found that diabetes mellitus was more common in patients in the highest quartile of LLAC scores (p = 0.039).