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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2013  |  Volume : 24  |  Issue : 6  |  Page : 1189-1194
Risk factors of chronic Kidney disease influencing cardiac calcification

1 Department of Nephrology, Madras Medical Mission Hospital, Chennai, India
2 Department of Radiology, Sri Ramachandra University, Chennai, India

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Date of Web Publication13-Nov-2013


We sought to determine the influence of risk factors of chronic kidney disease (CKD) on cardiac calcification. We studied the correlation between coronary artery calcium score (CACS) and the type and duration of dialysis as well as the presence of diabetes mellitus and hypertension. The relation between calcium score and mortality was also analyzed. Patients with CKD attending the outpatient department or admitted in our hospital were included. They were subjected to high-resolution computerized tomography of the thorax to determine their CACS. Serum levels of intact parathyroid hormone (iPTH), highly sensitive C-reactive protein (hCRP), homocysteine, calcium, phosphorus, and calcium × phosphorus product were measured. Out of the 50 patients studied, 39 were hypertensive (78%), 32 were diabetic (64.4%), 20 were on hemodialysis, and 13 were on continuous ambulatory peritoneal dialysis. The mean CACS was 388.6. Twenty-nine patients had high iPTH levels and 92.9% of them had calcium score >400 (P = 0.013). Twenty-eight patients had high hCRP and 85.7% of these patients had calcium score >400 (P = 0.048). Patients on dialysis for more than two years had higher calcium score >400 (P = 0.035). 43% of diabetics had calcium score >400 (P = 0.008). All the six patients who died had calcium score >400 (P = 0). There was statistically no significant association noted between hypertension, high calcium x phosphorus product, and high homocysteine levels, and high calcium score. Our study suggests that higher values of iPTH, hCRP, and longer duration on dialysis are associated with accelerated cardiac calcification. Calcification scores >400 are associated with increased mortality.

How to cite this article:
Iyer H, Abraham G, Reddy YN, Pandurangi UM, Kalaichelvan U, Gomathi S B, Mathew M, Santhosham R. Risk factors of chronic Kidney disease influencing cardiac calcification. Saudi J Kidney Dis Transpl 2013;24:1189-94

How to cite this URL:
Iyer H, Abraham G, Reddy YN, Pandurangi UM, Kalaichelvan U, Gomathi S B, Mathew M, Santhosham R. Risk factors of chronic Kidney disease influencing cardiac calcification. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2021 Mar 3];24:1189-94. Available from: https://www.sjkdt.org/text.asp?2013/24/6/1189/121279

   Introduction Top

There is a rising incidence and prevalence of chronic kidney disease (CKD). Increasing evidence, accrued in the past decades, indicates that the adverse outcomes of CKD, such as cardiovascular disease and premature death, can be prevented or delayed. In patients on chronic peritoneal dialysis in India, the dropout rate was 51% in the first year in the 90s, and the major cause of death was sudden cardiac death, congestive cardiac failure, or myocardial infarction. [1] Cardiac calcification is a surrogate marker of coronary artery disease (CAD) and correlates directly with the amount of coronary plaque. Coronary artery calcification is premature and accelerated in CKD, increases over time, and is inversely proportional to the glomerular filtration rate (GFR). [2],[3] The presence and extent of cardiac calcification are strong predictors of cardiovascular and all-cause mortality [4] [Figure 1]. Dysregulation of mineral metabolism may influence the risk for cardiac calcification. [5] Increasing age, a family history of premature ischemic heart disease, and some non-invasive markers are useful predictors of coronary disease. [6] Cardiovascular disease accounts for more than 50% of deaths among persons with CKD, and the annual cardiovascular mortality rate is greater than in the non-CKD population. [7] Recently, interest has focused on the roles of hyperphosphatemia, elevated levels of the calcium × phosphorus product (CPP), and hyperparathyroidism in the development of cardiovascular disease in CKD. Goodnab et al recently demonstrated a high prevalence of coronary artery calcification among young adults receiving dialysis, especially those who had been receiving dialysis for more than ten years. [8]
Figure 1: Multi-helical high-resolution computerized tomography showing three-vessel coronary artery calcification in a patient with end-stage renal disease.

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   Methods Top

The subjects enrolled in this study consisted of a mixed group of patients having CKD. Each patient was examined in detail with particular attention to history, symptoms, and physical findings. The control group consisted of persons with no clinical or laboratory evidence of CKD or vascular disease and were matched by age and gender.

The age, gender, presence of diabetes and hypertension, duration on dialysis (dialysis vintage), type of dialysis, level of serum albumin, CPP, vitamin D usage, anemia, erythro-poietin usage, lipid levels, intact parathyroid hormone (iPTH) level, highly sensitive C-reactive protein (hCRP) level, and homocysteine level were noted for all patients. The presence of atherosclerotic vascular disease (documented by the clinical diagnosis of CAD including a history of myocardial infarction, angina pectoris, or presence of Q waves on electrocardiogram, or evidence of obstructive disease by angiography), cerebrovascular disease (a history of thrombotic stroke or transient ischemic attack), or peripheral vascular disease (history of claudication or lower extremity revascularization) was noted. Informed consent was obtained from all subjects. Subjects with the following were excluded from participation: acute coronary syndrome and severe congestive heart failure, serious gastrointestinal disease, drug dependence or abuse, and active malignancy.

Imaging procedure

Rapid multi-slice complete thin sections of the heart and great vessels were taken using multi-helical high-resolution computerized tomography (HRCT) at every 1.25 mm. No contrast was used. All areas of calcification with a minimal density of 130 Hounsfield units within the borders of the coronary arteries, aorta, mitral and aortic valves were computed to determine the coronary artery calcium score (CACS). A calcified plaque was considered to be present if at least three contiguous pixels with a density of ≥130 Hounsfield units were measured (an area equivalent to 1.03 mm 2 ). The total volume and density of calcification were derived in the following areas: coronary arteries (left main, left anterior descending, left circumflex and right coronary artery), aorta, mitral and aortic valves. The calcium score was calculated as originally described by Agatston et al, which incorporates the density of calcification [Figure 1], multiplying the calcification volume by a weighted density coefficient. Scans were considered of acceptable research quality only if the images were free from artifacts due to motion, respiration, or asynchronous electrocardiographic triggering. Repeat scanning was not required in any case.

   Statistical Analysis Top

For descriptive purposes, subjects were classified into five coronary calcification groups based on the severity of calcification [Table 1] and the CACS values were compared between cases and controls [Figure 2]. The comparison of CACS between the risk factors was made [Figure 3]. All reported P values were based on two-tailed tests of statistical significance. Descriptive statistics was used for all quantitative data [Table 2]. Student's t-test was used for tests for significant difference in mean (mean ± standard deviation). Chi-square test and association was used to find the relationship between CACS (<400 or >400) and other variables.
Table 1: Coronary artery calcification according to severity.

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Table 2. The demographic and laboratory data of the study patients.

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Figure 2. Comparison of cases and controls with respect to coronary artery calcium score value.
CACS: Coronary artery calcium score

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Figure 3. Comparison of coronary artery calcium score <400 and ≥400 between the various risk factors for coronary artery disease.

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   Results Top

Six patients died during a 2-year follow-up, all of whom had a CACS >400 (P = 0); four of these patients were on hemodialysis (HD) and two were on continuous ambulatory peritoneal dialysis (CAPD). Among the patients with diabetes (n = 32; 64.4%), the mean CACS was 589.2 (P = 0.008). Of these, 19 patients (44.2%) had diabetes for >5 years [their mean CACS was 592 (P = 0.03)]. Among these 19 patients, nine had CACS >400 (P = 0.065).

Among the patients with hypertension (n = 39; 78%), the mean CACS was 419.5. Twenty-five patients had a score ≤400 and 14 had a score >400 (P = 0.145). Among the 14 patients who had hypertension for >5 years, six had a score >400 (P = 0.317).

Four patients (8%) had CPP >55 (mean CACS 432.3). Of these, two had a CACS >400 (P = 0.434).

Ten patients (20%) had homocysteine levels more than 10 umol/L. Of these, six had a score >400 (P = 0.129).

   Discussion Top

The presence and severity of cardiac calcification has been shown to be inversely associated with coronary vasodilatory response and has been found to be responsible for coronary events. [9] Cardiac calcification was identified for the first time in 2003 as a cardiovascular disease risk factor and as an independent predictor of mortality. [10] The extent of cardiac calcification in CKD is significantly greater than in non-CKD patients with established CAD. [11] Cardiac calcification score provides incremental information independent of traditional risk factors on all-cause mortality risk. [12] The prevalence of hypertension and diabetes is high in patients on dialysis and they make a major contribution to the increasing mortality.

In a cross-sectional study, it was shown that there is a high prevalence of cardiac calcification in maintenance HD patients, and an association between cardiac calcification and age, diabetes, and mineral metabolism abnormalities was also seen. [13] Our findings are in agreement with this as far as diabetes and mineral metabolism are concerned. The authors of the study found CPP to be a strong predictor of cardiac calcification at lower values than previously reported. Although we also found a similar trend, statistical significance was not reached.

Toro et al reported a prevalence of cardiac calcification greater than 50% in CKD patients undergoing regular HD. [14] The value in diabetic patients appeared to be statistically significant. All our results are comparable to this study.

Raggi et al found that the extent of cardiac calcification was more pronounced with older age, male gender, diabetes, longer dialysis vintage, and higher CPP. Although our study did not match these values as far as age and sex are concerned, there was a statistically significant relation between the extent of CACS and the duration on dialysis. We found no relation between anemia and serum albumin levels. [5]

In concurrence with other studies, [15] we found higher CACS in our dialysis population. In addition, we also found a statistically significant correlation between iPTH levels and the calcium scores. In 29 patients with iPTH levels >72 pg/mL, 92.9% had CACS >40 (P = 0.013), placing them at a higher risk for cardiovascular events, morbidity, and mortality, which matches with the findings of Alfrey. [16]

We also found that diabetic patients had higher CACS. Among the 32 diabetic patients, the mean CACS was 589.2. Of these, 14 had scores >400 (P = 0.008). This would suggest that the presence of diabetes mellitus places patients at a higher risk of developing cardiac calcification and cardiovascular events.

However, the limitations to our study should be noted. It is a cross-sectional and observational study; thus, only association, and not causality, can be established. Second, compared to what has been previously reported, CPP >55 did not prove to be the optimal value in terms of sensitivity and specificity to predict cardiac calcification in our patient population. This value is not easy to achieve in a clinical setting. For this reason, additional prospective controlled studies are warranted to confirm these observational results and to better define optimal CPP values to reduce the risk of cardiac calcification in the maintenance HD population. Finally, HRCT of thorax was used to determine CACS. This was due to the non-availability of electron beam computerized tomography (EBCT) at our center.

   Conclusions Top

Cardiovascular morbidity and mortality in patients with CKD have become a problem of epidemic dimension in our country. Cardiac calcification should be considered a marker of cardiovascular risk in dialysis patients. High CACS is a predictor of future coronary events. Factors such as increased hCRP, iPTH, and longer duration on dialysis accelerate the rate of cardiac calcification. Further studies are warranted to determine measures to retard the rate of progression of cardiac calcification.

   References Top

1.Abraham G, Padma G, Mathew M, Shroff S. How to set up a Peritoneal Dialysis Program: Indian Experience. Perit Dial Int 1999;19:184-6.  Back to cited text no. 1
2.Russo D, Palmiero G, De Blasio AP, Balletta MM, Andreucci VE. Calcification correlates directly to the amount of coronary plaque. Am J Kidney Dis 2004; 44:1024-30.  Back to cited text no. 2
3.Fox CS, Larson MG, Keyes MJ, et al. Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: The Framingham Heart Study. Kidney Int 2004;66:2017-21.  Back to cited text no. 3
4.Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, & cardiovascular risk in end-stage renal disease. Hypertension 2001;38:938-42.  Back to cited text no. 4
5.Raggi P, Boulay A, Chasan-Taber S, et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease & cardiovascular disease? J Am Coll Cardiol 2002;39:695-701.  Back to cited text no. 5
6.Varghese K, Cherian G, Abraham UT, Hayat NJ, Johny KV. Predictors of coronary disease in patients with end stage renal disease. Ren Fail 2001;6:797-806.  Back to cited text no. 6
7.Fole RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998; 32 (5 Suppl 3):S112-9.  Back to cited text no. 7
8.Goodman WG, Goldin J, Kuizon BD, et al. Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342:1478-83.  Back to cited text no. 8
9.Wang L, Jerosch-Herold M, Jacobs DR Jr, Shahar E, Detrano R, Folsom AR; MESA Study Investigators. Coronary artery calcification and myocardial perfusion in asymptomatic adults. J Am Coll Cardiol 2006;48:1018-26.  Back to cited text no. 9
10.Proceedings from the 44 th Congress of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), June 2007.  Back to cited text no. 10
11.Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC. Electron beam CT in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kideny Dis 1996; 27:394-401.  Back to cited text no. 11
12.Budoff MJ, Shaw LJ, Liu ST, et al. Long-Term prognosis associated with coronary calcification observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860-70.  Back to cited text no. 12
13.Margarita R, Sagraria G, Alejandro J, Patricia D, Victor L. Heart valve calcification & calcium x phosphorus product in hemodialysis patients: Analysis of optimum values for its prevention. Kidney Int 2003;63:S115-8.  Back to cited text no. 13
14.Mercedes S, Toro N, Rafael M, Elena J. Vascular calcification in the uraemic patient: A cardiovascular risk? Kidney Int 2003;63:S119-21.  Back to cited text no. 14
15.Nitta K, Akiba T, Uchida K, et al. The Progression of vascular calcification & serum Osteoprotegerin Levels in patients on long - term hemodialysis. Am J Kidney Dis 2003;42: 303-9.  Back to cited text no. 15
16.Alfrey AC. The role of abnormal phosphorus metabolism in the progression of chronic kidney disease and metastatic calcification. Kidney Int 2004;66:S13-7.  Back to cited text no. 16

Correspondence Address:
Georgi Abraham
Chennai Transplant Center, Madras Medical Mission, Chennai 600 037
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DOI: 10.4103/1319-2442.121279

PMID: 24231482

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


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