Progression Of Coronary Calcification Research Articles

The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer

Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.

The fallacy of the calcium-phosphorus product

Scattered through the practice of medicine are dogmas with little or no scientific basis. One of these is the product of the serum calcium and phosphorus concentrations, the so-called calcium-phosphorus product or Ca x P. The assumption that ectopic calcification will occur when the product of the serum calcium and phosphorus concentrations exceeds a particular threshold has become standard practice in nephrology even though there is little scientific basis. Experimental support is lacking, the chemistry underlying the use of the product is oversimplified and the concept that ectopic calcification is simply the result of supersaturation is biologically flawed. The evidence that the Ca x P is an independent risk factor for mortality and morbidity is also questionable. Although ectopic calcification can occur in many sites, this review will focus on vascular calcification, as it is the most common site and the site most likely to affect patient outcomes.

Comparison of Progression of Coronary Calcium in Postmenopausal Women on Versus Not on Estrogen/Progestin Therapy

The prophylactic effect of postmenopausal hormone replacement therapy on coronary atherosclerosis remains controversial. We, therefore, examined the influence of combined estrogen/progestin therapy on the progression of coronary calcium as a marker of coronary atherosclerosis. We determined the extent of coronary calcium in 277 women (age 57 +/- 6 years, time after menopause 3.9 +/- 2.4 years, group I) at the beginning of hormone replacement therapy using multislice computed tomography. For quantification, we calculated the volume score. After an observation period of 3 years, we determined the progression of coronary calcium in a second scan. The results were compared with those from an age- and risk factor-adjusted group of postmenopausal women without hormone substitution (group II). No significant difference was found in the volume score (59 +/- 95 vs 58 +/- 88) or risk factor distribution between the 2 groups on study entry. In 56 women of group I and 52 women of group II, coronary calcium could be excluded on the initial scan (p = NS). After a mean observation time of 38.5 +/- 4.9 months, we observed no significant difference between the 2 groups regarding an increase in volume score (17 +/- 24 vs 19 +/- 27, p = NS) or the fraction of women with an increase in volume score (82.2% vs 84.2%). In conclusion, a reduced progression of coronary calcium in postmenopausal women on combined estrogen/progestin therapy could not be observed compared with a matched group of women without hormone substitution.

Prevention of diabetic vascular calcification by nifedipine, a dihydropyridine-based calcium channel blocker

Vascular calcification is a common feature in advanced atherosclerosis and also a predictor of future cardiovascular events such as unstable angina and myocardial infarction, especially in diabetes. There is a growing body of evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate in diabetes, exist within atherosclerotic lesions, thereby being implicated in the pathogenesis of accelerated atherosclerosis in diabetes. Indeed, we have previously shown that AGE - their receptor (RAGE) interaction could induce angiogenesis through autocrine production of vascular endothelial growth factor, suggesting its role for plaque formation and enlargement in diabetes. Furthermore, we have found that AGEs have the ability to induce the osteoblatic differentiation of pericytes, thus contributing to the development of vascular calcification as well. These observations suggest that the inhibition of AGE formation or blockade of the downstream signaling of RAGE may be a novel therapeutic target for the inhibition of vascular calcification in diabetic atherosclerosis. Since we, along with others, have shown that nifedipine inhibits glycation of low-density lipoprotein in vitro and blocks the AGE-induced RAGE expression in endothelial cells through its anti-oxidative properties, nifedipine could inhibit vascular calcification by blocking the AGE formation or the downstream signaling in diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis. Does nifedipine treatment slow down the progression of coronary calcification in diabetic patients? If the answer is yes, is this beneficial effect of nifedipine superior to that of other DHPs with equihypotensive properties? Does nifedipine treatment decrease expression levels of AGEs and RAGE in diabetic atherosclerosis? Is the unique effect of nifedipine on vascular calcification correlated with its AGE or RAGE-suppressing properties? These prospective studies will provide further valuable information whether nifedipine could prevent vascular calcification in diabetic atherosclerosis by blockade the AGE-RAGE signaling in vascular wall cells.

Assessment of Coronary Artery Disease by Cardiac Computed Tomography

This scientific statement reviews the scientific data for cardiac computed tomography (CT) related to imaging of coronary artery disease (CAD) and atherosclerosis. Cardiac CT is a CT imaging technique that accounts for cardiac motion, typically through the use of ECG gating. The utility and limitations of generations of cardiac CT systems are reviewed in this statement with emphasis on CT measurement of CAD and coronary artery calcified plaque (CACP) and noncalcified plaque. Successive generations of CT technology have been applied to cardiac imaging beginning in the early 1980s with conventional CT, electron beam CT (EBCT) in 1987, and multidetector CT (MDCT) in 1999. Compared with other imaging modalities, cardiac CT has undergone an accelerated …

Letter by Romanens and Miserez Regarding Article, “Effect of Intensive Versus Standard Lipid-Lowering Treatment With Atorvastatin on the Progression of Calcified Coronary Atherosclerosis Over 12 Months: A Multicenter, Randomized, Double-Blind Trial”

To the Editor: We read with great interest the report by Schmermund et al1 that failed to demonstrate a difference in progression of coronary calcium (CAC) in asymptomatic, nondiseased subjects when treated with 10 mg versus 80 mg atorvastatin for 12 months. The authors expected that in 471 patients, a significantly lower progression of CAC scores and differences between groups of patients treated with 10 mg versus 80 mg atorvastatin could be observed. The study by Schmermund et …

Tracking Coronary Calcification and Atherosclerotic Lesions in Patients with Stable Angina Pectoris Undergoing Nifedipine Therapy

Aims: The objective of the Coronary Calcification (CC) study was to determine in patients with chronic symptomatic coronary artery disease, if, in addition to standard therapy, nifedipine GITS, relative to placebo, would arrest or slow down the progression of calcium or the development of new atherosclerotic lesions in the coronary arteries. Methods and Results: The CC study was part of the ACTION trial. Multi-slice computerized tomography was used to measure and track the progression of CC. Five hundred and eighteen patients were included in this study. The changes in calcium score from baseline every 24 months, over a period of between 4.5 and 6 years, were similar in the nifedipine and placebotreatment groups (p = 0.8). Compared to placebo, more patients in the nifedipine group (71 vs. 60%) were free of new calcified atherosclerotic lesions during follow-up(p = 0.095). Conclusion: Nifedipine GITS was not effective in slowing down the progression of calcium in advanced atherosclerotic plaques in patients with stable angina pectoris. Although statistically not significant, Nifedipine demonstrated a trend in slowing down the development of new atherosclerotic lesions.

Coronary calcium progression rates with a zero initial score by electron beam tomography

Background A review of existing literature shows that for individuals with initial coronary calcium scores (CCS) of zero it would be reasonable to consider follow-up scanning no sooner than 3 years from the initial evaluation, however the data is very limited. In this study, we sought to determine the rate of new calcifications in patients initially presenting with a zero initial score on electron beam tomography (EBT). Methods and results We evaluated 710 physician-referred participants (253 women and 448 men, mean age = 56 ± 9 years [range = 29 to 93]) with no coronary artery calcium (CAC) at baseline electron beam tomography (EBT) scan. The participants underwent a follow-up scan at least 12 months apart. In our study, 248 (35%) were followed for 1–3 years, 256 (36%) for 3–5 years and 204 (29%) for > 5 years, respectively. Overall, more than half of the individuals (62%) did not develop any CAC (score remained zero) in the interim period, whereas only 2% had CAC progression > 50 during the follow-up. The overall median (interquartile range) and mean ± S.D. change/year in these individuals was 0 (0–0.8) and 1 ± 3, respectively. Only 11 (2%) had CAC progression/year of 11–50, whereas 3 (1%) had CAC change/year > 50. It is interesting to note that even among individuals with long-term follow-up (> 5 years), very few individuals (2%) had CAC progression > 50. Individuals with follow-up 3–5 years did not have a significantly higher odds ratio for CAC change > 10 ( p = 0.17) as compared to the reference group (follow-up of 1–3 years). All the other individuals who had a longer follow-up (> 5 years) had a significantly higher likelihood of CAC progression > 10 (OR = 6.6, 95% CI = 2.6–16.9, p < 0.0001) compared to the reference group. Conclusion In individuals with no detectable coronary calcium on an initial EBT scan, a repeat scan can be recommended no sooner than 5 years.

The natural history of coronary calcification progression in a cohort of nocturnal haemodialysis patients

End-stage renal disease (ESRD) is associated with a markedly increased cardiac calcification burden, as reflected by computed tomography scans of the heart. Nocturnal haemodialysis (NHD) is a novel form of renal replacement therapy which has multiple physiologic effects that may affect vascular calcification, including improvements in phosphate and uraemia control. The objective of the present study is the determination of the natural history of coronary calcification progression in patients converted to NHD, and the examination of the relationships between calcification risk factors and calcification progression in these patients. Thirty-eight ESRD patients were converted to NHD, and included in our observational cohort study. Coronary artery calcification scores (CACS) were documented at baseline and post-conversion (mean interscan duration 16+/-1 months). Other variables of interest included age, dialysis vintage, Framingham risk profile, phosphate binder and vitamin D usage, and plasma levels of calcium, phosphate and parathyroid hormone. Our cohort was stratified according to baseline calcification burden (minimal calcification: CACS < or = 10 vs significant calcification: CACS > 10). Twenty-four patients had baseline CACS < or = 10. These patients demonstrated no change in coronary calcification after 1 year of NHD (from 0.7+/-0.5 to 6+/-3, P = 0.1). Fourteen patients had higher initial CACS at baseline (1874+/-696), and demonstrated a non-significant 9% increase over 1 year to 2038+/-740 (P = 0.1). Plasma phosphate and calcium x phosphate product were significantly reduced, as were calcium-based phosphate binder and antihypertensive usage. Our study is the first to document CACS progression in a cohort of NHD patients. Further analysis of the effect of NHD on the physiology of cardiovascular calcification is required.

Inflammation, cardiovascular disease and nocturnal hemodialysis

There is a growing recognition that uremia is a proinflammatory condition. Chronic uremia-associated inflammation contributes to the pathogenesis of atherosclerosis, anemia and cardiovascular calcification in patients with end-stage renal disease (ESRD). Daily nocturnal hemodialysis (DNHD) is a form of frequent intensive renal replacement therapy that has multiple cardiovascular benefits. Here we will review the emerging data of DNHD on inflammation, coronary calcification and anemia management. Increasing the dose and frequency of dialysis by DNHD has been demonstrated, in both short and long-term studies, to reverse several important risk factors for adverse cardiovascular events in ESRD patients. In addition, there are preliminary data indicating the positive effects of DNHD on inflammatory cytokine profile, rate of coronary calcification progression and enhanced erythropoietin responsiveness. Augmentation of dialysis dose by DNHD may positively influence uremia-related inflammation. The role of intensive dialysis as a treatment for chronic inflammation requires further research.

Effect of Lipid Modification on Progression of Coronary Calcification

Coronary artery calcification (CAC) reflects the anatomic presence of coronary atherosclerosis and the relative burden of coronary artery disease (CAD). Higher levels of CAC are seen in the presence of CAD risk factors, older age, and chronic kidney disease. The lipid profile (primarily low HDL cholesterol, elevated triglycerides, elevated LDL cholesterol, and elevated total cholesterol) are important factors in the calcification process. The annual progression of CAC can be reduced from 25 to 30% to 0 to 6% with LDL cholesterol reduction caused by statins and possibly sevelamer. At treated LDL cholesterol levels somewhere below 100 mg/dl, several sources of data suggest the anatomic burden of CAD, including CAC, regresses. Additional supportive studies indicate that carotid intimal medial thickness and the volume of coronary atheroma also can be reduced by LDL cholesterol reduction in concert with elevation of HDL cholesterol. This article reviews the data in support of altering the natural history of CAC with lipid modification.

Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis

Hemodialysis patients are at increased risk for progressive coronary artery calcification; however, the development and progression of this disease process in patients new to hemodialysis is unknown. One hundred and twenty-nine patients new to hemodialysis were randomized to receive calcium containing phosphate binders or the noncalcium phosphate binder sevelamer hydrochloride. Subjects underwent electron beam computed tomography scanning (EBCT) at entry into the study and again at 6, 12, and 18 months. One hundred and nine patients underwent baseline and at least one additional assessment of coronary calcification. At baseline, 37% of sevelamer treated and 31% of calcium treated patients had no evidence of coronary calcification. No subject with a zero coronary artery calcium score (CACS) at baseline progressed to a CACS >30 over 18 months. Subjects with a CACS > 30 at baseline showed progressive increases in CACS in both treatment arms (P < 0.05 for each time point in both groups). Subjects treated with calcium containing phosphate binders showed more rapid and more severe increases in CACS when compared with those receiving sevelamer hydrochloride (P= 0.056 at 12 months, P= 0.01 at 18 months). New hemodialysis patients with no evidence of coronary calcification showed little evidence of disease development over 18 months independent of phosphate binder therapy. However, subjects with evidence of at least mild coronary calcification had significant progression at 6, 12, and 18 months. Use of calcium containing phosphate binders resulted in more rapid progression of coronary calcification than did use of sevelamer hydrochloride.

Can Treatment Slow Progression of Coronary Calcification

These researchers conducted a double-blind randomized trial to assess how daily combination therapy — atorvastatin (20 mg), vitamin C (1 g), and

Aggressive Versus Moderate Lipid-Lowering Therapy in Hypercholesterolemic Postmenopausal Women

Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins. In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344+/-55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean+/-SD percent LDL reductions were 46.6%+/-19.9% and 24.5%+/-18.5 in the intensive and moderate treatment arms, respectively (P<0.0001), and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3% and 58.8% of women, respectively (P<0.0001). The total CVS% change was similar in the 2 treatment groups (median 15.1% and 14.3%, respectively; P=NS), and single-artery CVS% changes and absolute changes were also similar (P=NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression. In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD)

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD). Cardiovascular calcification (CVC) is commonly encountered both in the general population as well as in patients with end-stage renal disease (ESRD). The etiology of CVC in patients with ESRD is multifactorial. Despite that, current debate remains narrowly focused on the role of calcium loading from calcium-based phosphate binders (CBPB) in the pathogenesis and progression of CVC. Yet, the alleged link between these binders and CVC has not been substantiated in well-designed controlled trials. In contrast, the purported role of sevelamer, a non-calcium-based phosphate binder, in slowing the progression of CVC in dialysis patients has attracted widespread attention. The beneficial effect of sevelamer on progression of calcification was thought to be due to lower calcium loading during its use. However, an alternative and possibly more likely mechanism involves sevelamer-induced lowering of LDL cholesterol. In this context, previous studies in individuals with normal renal function have documented amelioration of coronary artery calcification (CAC) with reduction of LDL-cholesterol by treatment with HMG-CoA reductase inhibitors (statins). Given that CAC is a well-accepted marker of atherosclerosis, and that high plasma cholesterol concentration is one of the main risk factors for atherosclerosis, then it is not unreasonable to suspect that CAC may be halted or even reversed by lowering of LDL cholesterol level with statin therapy. Unfortunately, the effect of lowering the LDL-cholesterol level on CAC has not been studied in patients with ESRD. Therefore, conclusions about this important topic should await the results of well-designed clinical studies that control for all factors potentially implicated in the CVC burden of patients with ESRD. In this review, I will discuss the role of various potential mechanisms involved in the pathogenesis of CVC in patients with ESRD, and emphasize the role of dyslipidemia and its treatment in this important clinical entity.

Effects of Hormone Replacement on Progression of Coronary Calcium as Measured by Electron Beam Tomography

The recent Women's Health Initiative (WHI) results have demonstrated that combined estrogen plus progestin imparts a small but significant increase in cardiovascular risk and breast cancer among asymptomatic women. However, the effect and potential benefit of unopposed estrogen is not as clear. We sought to evaluate the progression of subclinical atherosclerosis in postmenopausal women using no hormone replacement therapy (HRT), combined therapy, and estrogen alone in an observational study. Postmenopausal women without symptoms or known coronary heart disease (CHD) were evaluated at our center for follow-up of coronary calcification. Patients were physician referred and underwent two consecutive electron beam tomography scans at least 1 year apart. All women fitting the study criteria were asked to participate, and those who consented were included. Demographic data, risk factors for CHD, HRT, and other medication use were collected by interview. The study included 177 asymptomatic women. Calcium progression was 14.6%+/-21% in women taking any hormone therapy (n=97). Annual calcium progression rates in nonusers (n=80) was 22.3%+/-32%. Relative to the nonuser group, HRT treatment inhibited the progression of atherosclerosis by 35% (p=0.01). This effect was independent of age, risk, cardiovascular factors, statin use, or baseline CAC score. Thirty-five of the 97 women (36%) were taking estrogen plus progestin, with an annual increase in calcium scores of 24%+/-23%, similar to the non-HRT women (22%). Those women taking estrogen replacement only (n=62) was 63% lower (9%+/-22%). This is an observational study, and the results are in accordance with the recently published WHI study, demonstrating no benefit of estrogen plus progestin compared with no therapy. However, women taking unopposed estrogen demonstrated a significant slowing of subclinical atherosclerosis compared with non-HRT and estrogen plus progestin.

Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events. The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking. We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]). Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.

Progression of Coronary Artery Calcium and Occurrence of Myocardial Infarction in Patients With and Without Diabetes Mellitus

Progression of coronary artery calcium, a marker of atherosclerosis, can be slowed with statins, and continued progression of calcium is associated with an increased risk of myocardial infarction. However, it is not known whether statins are effective in slowing calcium progression in diabetes mellitus. In a retrospective study, we examined 1153 nondiabetic and 157 diabetic subjects who underwent sequential electron beam tomography scans at a minimum 1-year interval to assess progression of coronary calcium. A yearly score increase >15% was considered evidence of true progression. The use of statins and occurrence of myocardial infarction were recorded. There was no difference in baseline calcium score between diabetic and nondiabetic patients. Diabetic patients with no coronary calcium on the baseline scans developed it more often than nondiabetic subjects (42% versus 25%; P=0.046) during follow-up. Calcium progression was 33% greater in diabetic patients than nondiabetic subjects (P<0.001) if no statin therapy was provided and 17.7% greater when statins were used (P<0.001). Among the 49 subjects who experienced a myocardial infarction, the calcium score increased on average 20% more in diabetic than nondiabetic patients (P<0.001). In logistic models, diabetes mellitus and systemic hypertension were the best predictors of calcium progression (odds ratio, 3.1 and 1.9, respectively), whereas baseline calcium score percentile and statin therapy were the best predictors of infarction. These findings support the notion that diabetes mellitus causes accelerated atherosclerosis, even in the presence of statin therapy, and provide evidence that coronary calcium monitoring is an effective method to assess treatment efficacy.

Diabetes and progression of coronary calcium under the influence of statin therapy

Coronary artery calcium (CAC) is a sensitive marker for the detection of coronary heart disease (CHD). Coronary artery calcification can be accurately quantified using electron beam tomography (EBT). We sought to evaluate the progression of atherosclerosis in asymptomatic persons with type 2 diabetes and measure the influence of statin therapy on CAC progression. We evaluated 163 asymptomatic patients with type 2 diabetes (120 men, 43 women). Patients were physician referred and underwent 2 consecutive EBT scans at least 1 year apart. Demographic data, risk factors for CHD, and medication use were collected. Patients with symptoms or known CHD were excluded. The mean age was 65 +/- 10 years. The mean CAC score at baseline was 651 +/- 414. Only 9 (6%) of 163 of participants had scores of 0 at baseline. The time between scans averaged 27 +/- 15 months. Patients not treated with statins demonstrated a median annual increase in CAC progression of 20% (4%-44%), whereas statin-treated patients demonstrated increase of 10% (4%-25%) (P = .0001). Hemoglobin A 1c was weakly associated with CAC progression. Asymptomatic diabetic patients show a high prevalence of atherosclerosis based on high frequency of coronary calcification. Statin therapy induced a 50% reduction in the rate of CAC progression. As rapid CAC progression has been associated with coronary events, EBT may serve as a noninvasive method for following atherosclerosis and response to therapy.

Modeling the implications of changes in vascular calcification in patients on hemodialysis

The Treat-to-Goal Study found that sevelamer slowed the progression of coronary calcification in patients on hemodialysis compared to calcium-based phosphate binders. To understand the implications of this effect for cardiovascular events, risk equations are needed. Data on 179 patients on hemodialysis treated at one center in France included biochemical values during the year prior to study entry, patient characteristics, and cardiovascular events over an average of 4 years. As arterial calcification was evaluated ultrasonographically and quantified using a 0 to 4 score, an equation relating this to the electron-beam tomography (EBT)-based calcification score used in the trial was developed and applied to all patients. The estimated scores were then used in survival and Cox proportional hazards analyses of cardiovascular events in relation to the degree of calcification, controlling for other characteristics. Mean age at inclusion was 54 years, dialysis vintage 70 months, average follow-up 49 months; 32% suffered an event. The calcification score, diabetes, C-reactive protein (CRP), diastolic blood pressure, gender, smoking and hypertension are independent predictors of cardiovascular risk. The resulting equation indicates that, relative to a calcification score below 400, the risk of an initial event increases 44% for a score of 600, and more than doubles for a score of 1000. In the absence of long-term follow-up studies, these equations permit quantification of the expected long-term clinical consequences of the impact of various phosphate binders on vascular calcification. Together with resource use and cost information, these equations are key inputs for formal cost-effectiveness analyses.