Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients
2006; Elsevier BV; Volume: 70; Issue: 9 Linguagem: Inglês
10.1038/sj.ki.5001820
ISSN1523-1755
AutoresAntonio Bellasi, Emiliana Ferramosca, Paul Muntner, Carlo Ratti, Rachel P. Wildman, Geoffrey A. Block, Paolo Raggi,
Tópico(s)Dialysis and Renal Disease Management
ResumoVascular calcification is associated with an adverse prognosis in end-stage renal disease. It can be accurately quantitated with computed tomography but simple in-office techniques may provide equally useful information. Accordingly we compared the results obtained with simple non-invasive techniques with those obtained using electron beam tomography (EBT) for coronary artery calcium scoring (CACS) in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement of pulse pressure (PP). Calcification of the abdominal aorta was semiquantitatively estimated with a score (Xr-score) of 0–24 divided into tertiles, echocardiograms were graded as 0–2 for absence or presence of calcification of the mitral and aortic valve and PP was divided in quartiles. The CACS was elevated (mean 910±1657, median 220). The sensitivity and specificity for CACS≥100 was 53 and 70%, for calcification of either valve and 67 and 91%, respectively, for Xr-score ≥7. The area under the curve for CACS≥100 associated with valve calcification and Xr-score was 0.62 and 0.78, respectively. The likelihood ratio (95% confidence interval) of CACS≥100 was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for participants with an Xr-score ≥7. In contrast, no association was present between PP and CACS. In conclusion, simple measures of cardiovascular calcification showed a very good correlation with more sophisticated measurements obtained with EBT. These methodologies may prove very useful for in-office imaging to guide further therapeutic choices in hemodialysis patients. Vascular calcification is associated with an adverse prognosis in end-stage renal disease. It can be accurately quantitated with computed tomography but simple in-office techniques may provide equally useful information. Accordingly we compared the results obtained with simple non-invasive techniques with those obtained using electron beam tomography (EBT) for coronary artery calcium scoring (CACS) in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement of pulse pressure (PP). Calcification of the abdominal aorta was semiquantitatively estimated with a score (Xr-score) of 0–24 divided into tertiles, echocardiograms were graded as 0–2 for absence or presence of calcification of the mitral and aortic valve and PP was divided in quartiles. The CACS was elevated (mean 910±1657, median 220). The sensitivity and specificity for CACS≥100 was 53 and 70%, for calcification of either valve and 67 and 91%, respectively, for Xr-score ≥7. The area under the curve for CACS≥100 associated with valve calcification and Xr-score was 0.62 and 0.78, respectively. The likelihood ratio (95% confidence interval) of CACS≥100 was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for participants with an Xr-score ≥7. In contrast, no association was present between PP and CACS. In conclusion, simple measures of cardiovascular calcification showed a very good correlation with more sophisticated measurements obtained with EBT. These methodologies may prove very useful for in-office imaging to guide further therapeutic choices in hemodialysis patients. Calcification of vessels and valves is highly prevalent in maintenance hemodialysis patients and has been associated with an increased risk of cardiovascular as well as all-cause mortality.1.Blacher J. Guerin A.P. Pannier B. et al.Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease.Hypertension. 2001; 38: 938-942Crossref PubMed Scopus (1237) Google Scholar The extent of calcification can be accurately quantified with sophisticated radiological techniques such as electron beam tomography (EBT).2.Agatston A.S. Janowitz W.R. Hildner F.J. et al.Quantification of coronary artery calcium using ultrafast computed tomography.J Am Coll Cardiol. 1990; 15: 827-832Abstract Full Text PDF PubMed Scopus (5739) Google Scholar In the general population, calcium scores derived with EBT have been shown to add incremental prognostic information to traditional risk factors for the prediction of hard events.3.Arad Y. Goodman K.J. Roth M. et al.Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study.J Am Coll Cardiol. 2005; 46: 158-165Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar, 4.LaMonte M.J. FitzGerald S.J. Church T.S. et al.Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women.Am J Epidemiol. 2005; 162: 421-429Crossref PubMed Scopus (264) Google Scholar, 5.Shaw L.J. Raggi P. Schisterman E. et al.Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality.Radiology. 2003; 228: 826-833Crossref PubMed Scopus (754) Google Scholar Similar but weaker evidence has been published in a hemodialysis study.6.Matsuoka M. Iseki K. Tamashiro M. et al.Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis.Clin Exp Nephrol. 2004; 8: 54-58Crossref PubMed Scopus (217) Google Scholar Sequential EBT scanning has also been utilized to follow the progression of vascular and valvular calcification in subjects with normal renal function as well as uremic patients.7.Pohle K. Maffert R. Ropers D. et al.Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors.Circulation. 2001; 104: 1927-1932Crossref PubMed Scopus (362) Google Scholar, 8.Block G.A. Spiegel D.M. Ehrlich J. et al.Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis.Kidney Int. 2005; 68: 1815-1824Abstract Full Text Full Text PDF PubMed Scopus (719) Google Scholar, 9.Chertow G.M. Burke S.K. Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.Kidney Int. 2002; 62: 245-252Abstract Full Text Full Text PDF PubMed Scopus (1330) Google Scholar, 10.Raggi P. Bommer J. Chertow G.M. Valvular calcification in hemodialysis patients randomized to calcium-based phosphorus binders or sevelamer.J Heart Valve Dis. 2004; 13: 134-141PubMed Google Scholar Although quantitatively accurate, both EBT and the more modern multidetector computed tomography (CT) technologies are expensive, deliver a substantial dose of radiation, and cannot be easily performed in an ambulatory setting. As the presence of calcification has important prognostic and therapeutic implications, the Global Bone and Mineral Initiative11.Goodman W.G. London G. Amann K. et al.Vascular calcification in chronic kidney disease.Am J Kidney Dis. 2004; 43: 572-579Abstract Full Text Full Text PDF PubMed Scopus (370) Google Scholar recently proposed that a series of simple in-office measurements and assessments might be substituted for EBT and multidetector CT to identify and semiquantitatively assess the extent of cardiovascular calcification in patients suffering from end-stage renal disease. This group of experts suggested that a plain lateral X-ray of the lumbar spine (Figure 1) to assess the presence of calcification of the abdominal aorta,12.Kauppila L.I. Polak J.F. Cupples L.A. et al.New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study.Atherosclerosis. 1997; 132: 245-250Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar the measurement of pulse pressure (PP),13.Klassen P.S. Lowrie E.G. Reddan D.N. et al.Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis.JAMA. 2002; 287: 1548-1555Crossref PubMed Scopus (360) Google Scholar and the performance of an echocardiogram to visualize calcification of the cardiac valves14.Wang A.Y. Wang M. Woo J. et al.Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study.J Am Soc Nephrol. 2003; 14: 159-168Crossref PubMed Scopus (366) Google Scholar might provide useful diagnostic and prognostic information. These three techniques were therefore proposed as a substitute for the more sophisticated and expensive CT imaging tools because of their demonstrated prognostic significance.11.Goodman W.G. London G. Amann K. et al.Vascular calcification in chronic kidney disease.Am J Kidney Dis. 2004; 43: 572-579Abstract Full Text Full Text PDF PubMed Scopus (370) Google Scholar Accordingly, the aim of this study was to compare the information derived with EBT and simple in-office approaches to demonstrate the presence and extent of cardiovascular calcification in a cohort of prevalent hemodialysis patients. Overall, there were an equal number of men and women. Caucasians and African Americans were the most common race-ethnicity groups (40 and 53%, respectively) with only 7% of other races. The mean dialysis vintage was 2.7 years and hypertension and diabetes mellitus were highly prevalent (95 and 50%, respectively). The mean (±s.d.) abdominal aorta X-ray score was 4.4±5.7 (median 1, inter-quartile range 0–7). The mean systolic arterial pressure was elevated at 146±26 mmHg with a mean diastolic pressure of 78±14.5 mmHg and a mean PP of 57±18 mmHg. On EBT imaging, 24 patients did not have any coronary artery calcium and 18 had a coronary artery calcium score (CACS)<30. The distribution of CACS categories in the study population is shown in Figure 2. The median CACS was high (220; inter-quartile range 19–899). Table 1 shows the clinical characteristics of the study population according to CACS categories. On average, participants with higher coronary artery scores were older, more likely to have a history of atherosclerotic cardiovascular disease, and had higher abdominal aorta X-ray scores.Table 1Study population characteristics by coronary artery calcium scoreCoronary artery calcium score on EBT0–29 (n=42)30–99 (n=16)100–399 (n=27)400–999 (n=26)≥1000 (n=29)P-trendAge (years)46.7 (14.7)54.8 (13.1)56.6 (15.1)62.5 (10.8)60.5 (12.0)<0.001Women (%)58.156.350.046.445.50.119African American (%)53.562.546.450.054.60.864Diabetes mellitus (%)41.950.042.957.163.60.122BMI (kg/m2)26.5 (5.4)26.8 (5.6)26.0 (5.4)26.1 (4.8)27.1 (6.1)0.880Current smoking (%)12.220.011.118.531.30.209History of ASCVD (%)14.043.839.367.945.5<0.001SBP (mmHg)146.0 (23.1)143.6 (22.4)145.4 (29.5)151.2 (26.3)144.8 (26.3)0.819DBP (mmHg)81.8 (15.7)80.1 (12.4)74.4 (15.2)80.3 (12.9)74.4 (14.1)0.061Pulse pressure (mmHg)64.2 (16.4)63.6 (19.7)71.1 (26.7)70.8 (21.4)70.3 (20.4)0.111Abdominal aorta X-Ray score0.90 (2.02)2.19 (3.58)5.37 (5.61)6.62 (6.65)7.66 (6.58)<0.001Valvular calcification Aortic valve (%)33.325.029.653.975.9<0.001 Mitral valve (%)32.625.048.219.259.40.084ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; DBP, diastolic blood pressure; EBT, electron beam tomography; SBP, systolic blood pressure.Parentheses indicate s.d. Open table in a new tab ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; DBP, diastolic blood pressure; EBT, electron beam tomography; SBP, systolic blood pressure. Parentheses indicate s.d. Figure 3 shows the prevalence of valvular calcification identified by echocardiography in patients categorized according to various CACS thresholds. Figure 4 shows the prevalence of various levels of CACS by quartile of PP and abdominal aorta X-ray score. Patients with mitral and aortic valve calcification and higher abdominal aorta X-ray scores were consistently more likely to have higher CACSs.Figure 4Prevalence of coronary artery calcium score ≥30, ≥100, ≥400, and ≥1000 by quartile of PP and level of abdominal aorta calcification.View Large Image Figure ViewerDownload (PPT) Table 2 show the sensitivity, specificity, likelihood ratios, and area under the curve for PP, valve calcification, and abdominal aorta Xr scores in the prediction of CACS≥30, ≥100, ≥400, ≥1000. The presence and extent of valve calcification and abdominal aorta calcification were associated with progressively higher likelihood ratios of each CACS category. For example, the likelihood ratio (95% confidence interval) of CACS≥100 for patients with 1 and 2 calcified valves was 1.79 (1.09, 2.96) and 1.88 (1.05, 3.39), respectively, and 2.53 (1.49, 4.28) and 7.50 (2.89, 19.5) for patients with an abdominal aorta X-ray score of 1–6 and ≥7, respectively. Additionally, the area under the curve for abdominal Xr-scores was above 0.70 for predicting each CACS level indicating very good discriminatory value. The area under the curve for valve calcification increased from 0.58 for a CACS≥30 to 0.72 for a CACS≥1000 indicating fair to good discriminatory value. In contrast, the test properties for PP showed very low accuracy in predicting CACS.Table 2Test properties, likelihood ratios, and area under the curve associated with PP, valve, and abdominal aorta calcification predicting the presence of CACSSensitivity (%)Specificity (%)Likelihood ratioArea under curveOutcome – CACS≥30Pulse pressure0.50 Quartile 249410.83 (0.53, 1.30) Quartile 345430.78 (0.48, 1.27) Quartile 450531.06 (0.60, 1.88)Calcified valves0.58 146651.32 (0.78, 2.21) 242731.56 (0.81, 3.01)Abdominal aorta calcification0.78Abdominal X-ray 1–654782.47 (1.33, 4.61)Abdominal X-ray 7–24599719.5 (2.80, 136)Outcome – CACS≥100Pulse pressure0.51 Quartile 248420.82 (0.53, 1.27) Quartile 344450.79 (0.49, 1.28) Quartile 451541.12 (0.66, 1.88)Calcified valves0.62 153701.79 (1.09, 2.96) 247751.88 (1.05, 3.39)Abdominal aorta calcification0.78Abdominal X-ray 1–661762.53 (1.49, 4.28)Abdominal X-ray 7–2467917.50 (2.89, 19.5)Outcome – CACS≥400Pulse pressure0.71 Quartile 246450.83 (0.51, 1.36) Quartile 352541.12 (0.69, 1.83) Quartile 450511.03 (0.63, 1.37)Calcified valves0.63 159661.76 (1.15, 2.69) 255731.99 (1.19, 3.32)Abdominal aorta calcification0.74Abdominal X-ray 1–664682.01 (1.30, 3.11)Abdominal X-ray 7–2473793.48 (2.07, 5.86)Outcome – CACS≥1000Pulse pressure0.48 Quartile 233440.60 (0.26, 1.37) Quartile 356541.21 (0.73, 2.01) Quartile 447500.93 (0.51, 1.71)Calcified valves0.72 173621.94 (1.30, 2.91) 278732.85 (1.84, 4.43)Abdominal aorta calcification0.72Abdominal X-ray 1–669631.88 (1.19, 2.97)Abdominal X-ray 7–2480702.63 (1.77, 3.93)CACS, coronary artery calcium score; NPV, negative predictive value; PP, pulse pressure; PPV, positive predictive value.Parentheses indicate 95% confidence intervals.Abdominal X-ray scores were calculated according to the scoring methodology proposed by Kauppila et al.12.Kauppila L.I. Polak J.F. Cupples L.A. et al.New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study.Atherosclerosis. 1997; 132: 245-250Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar (range: 0–24). Open table in a new tab CACS, coronary artery calcium score; NPV, negative predictive value; PP, pulse pressure; PPV, positive predictive value. Parentheses indicate 95% confidence intervals. Abdominal X-ray scores were calculated according to the scoring methodology proposed by Kauppila et al.12.Kauppila L.I. Polak J.F. Cupples L.A. et al.New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study.Atherosclerosis. 1997; 132: 245-250Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar (range: 0–24). These results suggest that a meaningful association exists between semiquantitative, office-based methods and sophisticated and quantitative methods to assess the extent of cardiovascular calcification. A strong association was present between abdominal aorta calcification on plain X-ray films and CACS. Also, valvular calcification was a good predictor of CACS. On the contrary, no pattern was present between PP and CACS. Although an increased PP may be a risk factor for unfavorable outcomes, it is likely a very remote surrogate marker of vascular calcification and depends on many more factors than vascular calcification alone. Furthermore, central aortic pressure may reflect more accurately vascular stiffness – and vascular calcification – and it is a an excellent marker of risk in the renal15.Safar M.E. Blacher J. Pannier B. et al.Central pulse pressure and mortality in end-stage renal disease.Hypertension. 2002; 39: 735-738Crossref PubMed Scopus (685) Google Scholar as well the general population.16.Williams B. Lacy P.S. Thom S.M. et al.Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes. Principal Results of the Conduit Artery Function Evaluation (CAFE) Study.Circulation. 2006; 113: 1213-1225Crossref PubMed Scopus (35) Google Scholar Our study results highlight the potential for greater and more global implementation of the kidney disease outcomes quality initiative (K/DOQI) guidelines on management of dialysis patients with cardiovascular calcifications that are considered a marker of risk and an indication for changes in therapeutic choices.17.K/DOQI Workgroup K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients.Am J Kidney Dis. 2005; 45: S1-S153Google Scholar Braun et al.18.Braun J. Oldendorf M. Moshage W. et al.Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients.Am J Kidney Dis. 1996; 27: 394-401Abstract Full Text PDF PubMed Scopus (737) Google Scholar were the first to utilize EBT to describe the large extent of coronary artery and valvular calcification in hemodialysis patients compared to age- and sex-matched individuals with and without coronary artery disease and intact renal function. Similar observations were reported in young patients undergoing dialysis,19.Goodman W.G. Goldin J. Kuizon B.D. et al.Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.N Engl J Med. 2000; 342: 1478-1483Crossref PubMed Scopus (2440) Google Scholar,20.Oh J. Wunsch R. Turzer M. et al.Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure.Circulation. 2002; 106: 100-105Crossref PubMed Scopus (635) Google Scholar and in a larger series of adult subjects.21.Raggi P. Boulay A. Chasan-Taber S. et al.Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?.J Am Coll Cardiol. 2002; 39: 695-701Abstract Full Text Full Text PDF PubMed Scopus (998) Google Scholar Utilizing EBT, the progression of valvular and vascular calcification was also shown to be rapid18.Braun J. Oldendorf M. Moshage W. et al.Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients.Am J Kidney Dis. 1996; 27: 394-401Abstract Full Text PDF PubMed Scopus (737) Google Scholar and to be inhibited with the non-calcium-based phosphate binder sevelamer.8.Block G.A. Spiegel D.M. Ehrlich J. et al.Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis.Kidney Int. 2005; 68: 1815-1824Abstract Full Text Full Text PDF PubMed Scopus (719) Google Scholar, 9.Chertow G.M. Burke S.K. Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.Kidney Int. 2002; 62: 245-252Abstract Full Text Full Text PDF PubMed Scopus (1330) Google Scholar, 10.Raggi P. Bommer J. Chertow G.M. Valvular calcification in hemodialysis patients randomized to calcium-based phosphorus binders or sevelamer.J Heart Valve Dis. 2004; 13: 134-141PubMed Google Scholar Given the negative prognostic impact of cardiovascular calcification and the possibility to slow its progression, the National Kidney Foundation has recommended screening for its presence with simple office-based methods to make it accessible to a wider audience of practicing physicians.11.Goodman W.G. London G. Amann K. et al.Vascular calcification in chronic kidney disease.Am J Kidney Dis. 2004; 43: 572-579Abstract Full Text Full Text PDF PubMed Scopus (370) Google Scholar This study shows that widely available office techniques may indeed be very helpful in assessing the presence of CACS. Furthermore, these simpler techniques may be appropriate for patients that are typically excluded from cardiac CT imaging owing to arrhythmias and excessive weight, although our investigation did not specifically address such populations. Nonetheless, CT remains a highly reliable research tool and it is very useful in the proper clinical context. Of interest, there was no difference in severity of CACS between white and black individuals, in contrast with recent literature showing a smaller quantity of coronary artery calcium in blacks, compared to whites, with normal renal function.22.McClelland R.L. Chung H. Detrano R. et al.Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA).Circulation. 2006; 113: 30-37Crossref PubMed Scopus (601) Google Scholar This suggests that hemodialysis may nullify any racial difference as far as the extent of CACS is concerned, probably due to processes that involve both medial as well as sub-intimal calcification. There were a few limitations to this study. The results of our investigation should be considered preliminary as the overall as well as the cardiovascular outcome related to the findings of the study are not known. However, the collection of information on all-cause mortality as well as cardiovascular events is ongoing. Although the population studied reflects rather accurately the typical hemodialysis population of North America, the high prevalence of diabetic patients and African American individuals should caution against the direct application of this information to populations of other continents. We have shown a very good correlation between simple markers of cardiovascular calcification proposed by the Global Bone and Mineral Initiative Executive Committee11.Goodman W.G. London G. Amann K. et al.Vascular calcification in chronic kidney disease.Am J Kidney Dis. 2004; 43: 572-579Abstract Full Text Full Text PDF PubMed Scopus (370) Google Scholar and the more sensitive, quantitative assessments of coronary calcification obtainable with CT. Screening hemodialysis patients for the presence of cardiovascular calcification with these less expensive and more readily available modalities will allow the practicing nephrologist to identify, with acceptable accuracy, patients at higher risk for cardiovascular events. In these patients, therapies directed at management of bone and mineral metabolism should be carefully modified according to guidelines.
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