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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Coronary artery,aortic wall,and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease

BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent and severe vascular and valvular calcification. We undertook this study to test the hypothesis that vascular and valvular calcification begins and is often severe long before diabetic renal disease progresses to ESRD. METHODS: A total of 32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of 18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic controls without renal disease, matched for age, gender, ethnicity, and the presence/absence of dyslipidemia, hypertension, and known coronary artery disease (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of coronary artery calcification was significantly greater among diabetic renal disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs. 10, P < 0.001) than the nondiabetic controls. The coronary artery calcification scores were significantly more severe among diabetic renal disease individuals than either the diabetic or nondiabetic controls. Among individuals with diabetic renal disease, the coronary artery calcification and aortic wall calcification scores were several-fold greater among those with known CAD than among those without. There was also a significantly greater prevalence of aortic and mitral valve calcification among diabetic renal disease individuals than nondiabetic controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001). Multivariate analysis using all three groups reproduced these findings and also consistently identified age and diabetic renal disease as additional predictors for the presence or severity of coronary artery and aortic wall calcification. CONCLUSION: In this first, systematic analysis among nondialyzed individuals with diabetic renal disease, these data demonstrate that vascular and valvular calcification is present and often severe long before the disease progresses to ESRD. The data also suggest that the coronary artery and aortic wall calcification may represent atherosclerosis.     

Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease

BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.     

Carotid atherosclerosis is a predictor of coronary calcification in chronic haemodialysis patients.

BACKGROUND: Coronary artery calcification scores (CACS) calculated by electron beam computed tomography (EBCT) have been correlated with atherosclerotic burden in the non-uraemic population. However, the validity of this test in chronic haemodialysis patients (HD) is currently uncertain. In the present cross-sectional study, associations between carotid atherosclerosis and coronary calcification in HD patients are investigated. METHODS: We studied 79 chronic HD patients (39 male, 40 female; mean age, 45+/-12 years). The mean time on HD was 68+/-54 months (range, 6-187 months). In these patients, we measured serum calcium, phosphorus, total cholesterol, cholesterol subgroups and iPTH levels. EBCT, echocardiography, and high-resolution B-mode carotid Doppler ultrasonography were also performed. RESULTS: Plaque-positive HD patients had significantly higher CACS than plaque-negative patients (851+/-199 vs 428+/-185, mean+/-SE, P = 0.006). Coronary calcification scores were correlated with serum phosphorus (r = 0.37; P = 0.001). Only 8 of the 24 HD patients without coronary calcification had carotid plaques (33%), whereas 34 of the 53 patients with coronary calcification had carotid plaques (64%) (P = 0.015). Carotid plaque scores were correlated with CACS (r = 0.40; P = 0.001). A stepwise linear regression (model r = 0.72; P<0.001) revealed that CACS (log-transformed data of CACS) was associated with age (P<0.001), time on dialysis (P = 0.004), serum phosphorus level (P = 0.016) and carotid plaque scores (P = 0.037). CONCLUSIONS: Atherosclerosis is independently associated with coronary artery calcification and with hyperphosphataemia in chronic HD patients. CACS appeared to be predictive of both coronary atherosclerosis and carotid atherosclerosis.     

Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography.

BACKGROUND: Coronary artery calcification (CAC) measured by electron beam computed tomography (EBCT) correlates with plaque burden, vessel stenosis and is predictive of future cardiac events in the general population. Extensive CAC has been described recently in dialysis cohorts. For the first time we studied the relationship between CAC and coronary angiographic findings in patients with chronic renal failure, on dialysis and after renal transplantation. METHODS: We studied 46 patients who all had an EBCT-derived Agatston coronary calcium score and a diagnostic coronary angiogram within a 12-month period. The mean age was 55.7+/-13.2 (SD) years (range 29-80). The mean duration of dialysis was 54.4 months (range 1-372). RESULTS: The mean CAC was 2370+/-352.8. The mean CAC in patients with an abnormal coronary angiogram (n = 35) was 2869.6+/-417.9, while that in patients with a normal coronary angiogram (n = 11) was 559.4+/-255.1 (P = 0.001 for the inter-mean comparison). Total CAC correlated with the number of diseased vessels (P = 0.0001) and with severity of atherosclerosis in all the vessels (P = 0.0001). The individual coronary artery calcification score correlated well with the severity of atherosclerotic coronary disease (P<0.0001 for all) in the left anterior descending, right coronary and circumflex arteries. Running a multivariate regression analysis for atherosclerosis burden, we found that the only predictor was CAC (r = 0.34, P = 0.0001). CONCLUSION: CAC is common and more severe in patients with chronic kidney disease. Although in chronic kidney disease patients CAC can occur in the absence of occlusive coronary atherosclerosis, our data suggest that, as in the general population, CAC in chronic kidney disease patients is associated with obstructive atherosclerosis and may therefore be associated with a worse outcome.     

Increased aortic arch calcification in patients older than 75 years: implications for carotid artery stenting in elderly patients

OBJECTIVE: Recent studies reveal a consistently higher periprocedural risk of stroke during carotid artery stenting in octogenarians compared with younger patients. The mechanisms accounting for this increased risk of embolization and stroke in elderly patients are poorly understood. We analyzed the calcium content and aortic arch type in a consecutive series of patients to determine whether aortic arch calcium content is related to either age or arch type classification. METHODS: Aortic arch calcium content and arch classification were examined in consecutive patients undergoing thoracic computed tomography scans. The calcium content of the aortic arch, measured from the aortic root to the descending thoracic aorta at the level of the carina, was determined by using a coronary calcium score grade. The aortic arch classification was determined by using two-dimensional and multiplanar image reconstructions. Linear regression and analysis of variance were used to determine the effect of age, arch classification, and patient comorbidity on aortic arch calcium content. RESULTS: The computed tomography scans of 94 patients were analyzed. There was a positive correlation between age and aortic arch calcium content; the mean calcium score (Agatston units) for patients increased by decade (age <50 years, 12.6 +/- 12.3, n = 18; age 50-59 years, 14.6 +/- 8.2, n = 21; age 60-69 years, 276 +/- 120, n = 17; age 70-79 years, 1382 +/- 366, n = 27; age > or =80 years, 3889 +/- 778, n = 11; P < .001). There was significantly more arch calcium in patients 75 years or older compared with patients younger than 75 years (2458 +/- 447 vs 145 +/- 49; P < .001). There was no effect of patient comorbidity on aortic arch calcium content. Patients with type II aortic arches were older and had a higher calcium content compared with patients with type I aortic arches (2028 +/- 546 vs 712 +/- 191; P = .01). Power analysis showed more than 99% power to detect differences between patients younger than 75 years and 75 years or older. CONCLUSIONS: Patients 75 years of age or older have significantly more aortic arch calcification compared with younger patients. Increased arch calcium content and type II aortic arches may be markers of increased potential for embolization during endovascular manipulation that transverses the aortic arch. Preprocedural determination of aortic arch calcification and morphology may help to further stratify periprocedural carotid artery stenting risk in elderly patients.     

Vascular function in patients with end-stage renal disease and/or coronary artery disease: a cardiac magnetic resonance imaging study

Decreased arterial compliance in end-stage renal disease (ESRD) is associated with increased cardiovascular risk. Our aim was to examine aortic compliance in patients with ESRD using cardiac magnetic resonance imaging (MRI) and to compare these with patients with advanced atherosclerotic disease who are known to be at high cardiovascular risk. We examined a total of 83 subjects matched for age: 24 had ESRD and were on dialysis therapy for 3+/-6 years, 24 had severe coronary artery disease (CAD), 11 had both ESRD and CAD (4+/-5 years on dialysis therapy), and 24 healthy subjects with no evidence of CAD. Vascular and cardiac function was assessed using cardiac MRI. Aortic compliance was significantly reduced in patients with CAD compared to control subjects (11.3+/-6.3 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml x 10(-3)/mm Hg, P=0.009). Patients with ESRD also exhibited significantly reduced aortic compliance compared to healthy controls (12.4+/-5.8 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml 10(-3)/mm Hg, P=0.012), whereas there was no significant difference in aortic compliance between patients with CAD and ESRD. Even in the absence of symptomatic CAD, patients with ESRD have significantly reduced aortic compliance compared to normal subjects. Patients with ESRD have equivalent aortic compliance to patients with advanced CAD. These findings suggest that a significantly reduced aortic compliance is one of many mechanisms promoting premature cardiovascular events in patients with ESRD compared to age-matched controls from the general population.     

Early results and characteristic problems associated with cardiac surgery in long-term dialysis patients

OBJECTIVE(S): To analyze early results and characteristic problems that develop after cardiac surgery on dialysis patients. METHODS: One hundred fourteen patients on maintenance dialysis underwent cardiac surgery. Their mean age was 63.5 +/- 9.7 years, and 87 (76%) were male. The causes of chronic renal failure were diabetes mellitus in 41 (36%) and chronic glomerulonephritis in 40 (35%). Patients had previously been on dialysis for a mean duration of 7.8 +/- 5.6 years (range; 0.25-24 years). RESULTS: Fourteen (12%) were emergent cases. Eighty six patients (75%) received isolated coronary artery bypass grafting (CABG), and 10 patients underwent operations in which CABG was combined with other cardiac procedures. Twelve patients (14%) of the isolated CABG patient group (86 patients) were restricted to non-clamping bypass procedure due to severe calcification of the ascending aorta. Calcification score, which was represented by the sum of all involved coronary artery segments, was also significantly higher in dialysis patients than in the control group (4.5 +/- 2.4 segments vs. 1.5 +/- 2.1 segments, p < 0.05). Hospital mortality was 8.8% (10/114) overall, and 7% (6/86) in isolated CABG patients. The causes of deaths were as follows: intestinal necrosis in 3, arrhythmia in 2, cerebral infarction in 1, low output syndrome in 1, and sepsis in 3 (mediastinitis, pneumonia, and prosthetic valve infection). CONCLUSIONS: Long-term dialysis is a major risk factor in cardiac surgery. However, because the surgical results proved to be acceptable, long-term dialysis patients should not be denied cardiac surgery.     

Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins

BACKGROUND: In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification. METHODS: To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values. RESULTS: The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by MacNeal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight (P=0.027). Positive immunostaining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P < or = 0.001), as was a history of coronary artery disease (P < 0.001), and diabetes (P=0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium x phosphorus product (P=0.032 and 0.037). The location of immunostaining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification. CONCLUSIONS: In patients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44%), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.     

Perioperative and mid-term results of coronary bypass surgery in patients undergoing chronic dialysis.

PURPOSE: The goal of this study was to evaluate perioperative and mid-term results of coronary artery bypass grafting (CABG) in patients with end-stage renal disease (ESRD). METHODS: Thirty-five consecutive dialysis patients who required CABG over a 5-year period were investigated retrospectively. RESULTS: Mean patient age was 62.5+/-11.5 years. The mean number of diseased vessels was 2.3W0.8. Off-pump CABG (OPCAB) was performed in 12 patients. The mean number of anastomoses per patient was 2.5+/-1.1. The perioperative mortality was 5.7%, and the average duration of hospitalization was 25.3+/-13.4 days. Overall 5-year survival rates were 63.7%. The cardiac-related 5-year survival rate was 89.3%, and the cardiac event-free rate was 51.7%. Multivariate analysis failed to identify any significant prognosticators for perioperative or long-term outcomes. The morbidity rate was significantly lower in patients undergoing OPCAB than in patients undergoing conventional CABG (8.3 vs. 47.8%; p=0.03). Perioperative mortality in the OPCAB group was 0%, and the average duration of hospitalization was shorter in the OPCAB group than in the conventional CABG group (19.7 days vs. 28.5 days; p=0.1). CONCLUSION: In the context of coronary artery bypass surgery, OPCAB produced better outcomes than conventional CABG procedure in patients undergoing chronic dialysis. Further-more, OPCAB procedure seems to offer a greater benefit to dialysis patients than non-dialysis patients.     

Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients

BACKGROUND: Cardiovascular disease is frequent and severe in patients with end-stage renal disease. Disorders of mineral metabolism may contribute by promoting cardiovascular calcification. METHODS: We conducted a randomized clinical trial comparing sevelamer, a non-absorbed polymer, with calcium-based phosphate binders in 200 hemodialysis patients. Study outcomes included the targeted concentrations of serum phosphorus, calcium, and intact parathyroid hormone (PTH), and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography. RESULTS: Sevelamer and calcium provided equivalent control of serum phosphorus (end-of-study values 5.1 +/- 1.2 and 5.1 +/- 1.4 mg/dL, respectively, P = 0.33). Serum calcium concentration was significantly higher in the calcium-treated group (P = 0.002), and hypercalcemia was more common (16% vs. 5% with sevelamer, P = 0.04). More subjects in the calcium group had end-of-study intact PTH below the target of 150 to 300 pg/mL (57% vs. 30%, P = 0.001). At study completion, the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects (coronary arteries 36.6 vs. 0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01, respectively). The median percent change in coronary artery (25% vs. 6%, P = 0.02) and aortic (28% vs. 5%, P = 0.02) calcium score also was significantly greater with calcium than with sevelamer. CONCLUSIONS: Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.     

Measurement of vascular calcification using CT fistulograms.

BACKGROUND: Vascular calcification (VC), precipitated by calcium and phosphate imbalance, is a major contributor to cardiovascular disease (CVD) in chronic kidney disease (CKD). Electron-beam computed tomography (EBCT) quantitatively assesses coronary artery calcification (CAC), with VC scores predictive of atherosclerosis and cardiac events in the general and CKD population. EBCT is not readily available but spiral CT can also provide quantitative assessment of the extent of VC. CT fistulograms can be used as initial investigation for arterio-venous fistula (AVF) problems in haemodialysis (HD). The images obtained include thoracic aorta, brachio-cephalic, subclavian and common carotid arteries which allow assessment of the extent of VC in these vessels. No study to date has combined the CT fistulogram with concurrent determination of VC. METHODS: We hypothesize that a single investigation for AVF management may also provide information on VC. We retrospectively analysed CT fistulograms on 28 HD patients determining VC scores (in Hounsfield units) in AVF, subclavian and carotid arteries and aorta. We correlated these scores with patient demographics, serum markers of mineral metabolism (time averaged for the period 6 months prior to CT) and calcium-based phosphate binders. RESULTS: Patients (60.7% male) had a median age of 59 years and 46.4% were diabetic. The mean duration of dialysis was 17.5 months. CT fistulograms showed predominantly aortic (75% of patients) and subclavian (75%) calcifications, with only 21.4% having carotid VC and minimal VC at the level of AVF. Median VC scores were 619.8 (0-1481.4) for aorta and 521.7 (0-1139.6) for subclavian (scores of >400 indicate severe atherosclerotic disease), but there was no significant correlation with serum markers or duration of HD. Increasing age correlated significantly with greater VC in aortic (R = 0.53, P = 0.003) and subclavian (R = 0.40, P = 0.03) vessels, as well as with the number of VC sites involved. CAC was present in most patients (89.3%) but CAC scores were not able to be determined because of cardiac movement. CONCLUSION: Concurrent determination of the degree of calcification in certain vessels may be possible from CT studies assessing AVF structure. VC scores provided by CT fistulograms could contribute to HD patient CVD risk assessment but studies with larger patient numbers are required to determine their relevance.     

The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients

BACKGROUND: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. METHODS: To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. RESULTS: The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. CONCLUSION: Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.     

Degree of carotid plaque calcification in relation to symptomatic outcome and plaque inflammation

OBJECTIVE: We undertook this study to quantitate differences in the degree of calcification between symptomatic and asymptomatic plaques removed at carotid endarterectomy (CEA) and to determine associated extent of plaque macrophage infiltration, a histopathologic feature of plaque instability. METHODS: CEA plaques (n = 48) were imaged at 1.25-mm intervals with spiral computed tomography (CT; 10-15 images per plaque). Indications for CEA were transient ischemic attack (n = 16), stroke (n = 5), amaurosis (n = 4), and critical asymptomatic stenosis (n = 23). The percent area calcification for each plaque was determined in spiral CT serial sections and averaged for each plaque. In 31 of 48 plaques macrophage infiltration was quantitated in corresponding histologic sections with immunohistochemical techniques. RESULTS: The mean (+/- SD) age of patients with symptomatic and asymptomatic plaques was 66 +/- 7 years vs 71 +/- 7 years, respectively, and degree of stenosis was 76% versus 82%, respectively (P =.05). Atherosclerosis risk factors were similar between groups. Percent plaque area calcification was twofold greater in asymptomatic versus symptomatic plaques (48% +/- 19% vs 24% +/- 20%, respectively; P <.05). At receiver operating characteristic curve analysis, 80% of symptomatic plaques were below and 87% of asymptomatic plaques were above a cutoff point of 30% plaque area calcification. Macrophage burden was greater in the symptomatic plaques than in the asymptomatic plaques (52% vs 23%; P <.03). A strong inverse relationship between the degree of plaque calcification and macrophage infiltration was found in critical carotid stenoses (r = -0.87; P <.001). CONCLUSIONS: Symptomatic plaques are less calcified and more inflamed than asymptomatic plaques. Regardless of clinical outcome, a strong inverse correlation was found between the extent of carotid plaque calcification and the intensity of plaque fibrous cap inflammation as determined by the degree of macrophage infiltration. Carotid plaque calcification is associated with plaque stability, and is a potential spiral CT in vivo quantitative marker for cerebrovascular ischemic event risk.     

Association of pelvic arterial calcification with arteriovenous thigh graft failure in haemodialysis patients.

BACKGROUND: Arterial calcification is a common problem in patients with chronic kidney disease, and has been associated with adverse clinical outcomes. The goal of the present study was to evaluate whether pelvic artery calcifications are associated with technical failure of arteriovenous thigh grafts in haemodialysis patients. METHODS: From 1 January 1999 to 30 June 2002, thigh grafts were placed in 54 haemodialysis patients who had exhausted all options for permanent vascular access in the upper extremities. Perioperative computed tomography (CT) of the abdomen and pelvis was obtained in 32 of the patients for diagnostic purposes unrelated to vascular access planning. Two radiologists, who were blinded to the graft outcomes, scored the vascular calcifications on CT of the distal aorta, common iliac, external iliac and common femoral arteries on a semi-quantitative 5-point scale. The association between technical graft failure (inability to complete the anastomosis) and the vascular calcification score was analysed. RESULTS: There was a high inter-observer agreement in scoring vascular calcification (kappa = 0.801). Among 26 patients with absent or mild pelvic arterial calcifications (grade 1-2) on CT, none (0%) experienced technical graft failure. In contrast, three of six patients (50%) with moderate to severe calcification (grade 3-5) had technical graft failures (P = 0.004 by Fisher's exact test). The cumulative 1 year graft patency was lower in the group with grade 3-5 calcification (33 vs 81%, P = 0.09). The two groups were similar in age, gender, race, diabetes, duration of dialysis, serum calcium, serum phosphorus and serum parathyroid hormone. CONCLUSION: There is a strong association between pelvic artery calcifications and technical failure of thigh grafts. The presence of moderate to severe vascular calcification is predictive of poor cumulative 1 year graft patency.     

Vascular calcification in South African dialysis patients: Ethnic variation, prevalence, detection and haemodynamic correlates

Aim: Studies from the US have shown little effect of ethnicity on vascular calcification in dialysis patients. This has not been examined in the multi‐ethnic population of South Africa where genetic and environmental differences may exist. We assessed the extent and severity of vascular calcification in South African dialysis patients according to race and known risk factors. We further evaluated the association of abdominal aorta calcification with coronary artery calcification. Method: Seventy‐five CKD‐5D patients and 20 healthy controls were enrolled consecutively. All subjects underwent chest computed tomography for coronary calcium score and abdominal X‐ray for abdominal aorta calcium score. Ambulatory blood pressure monitoring was generated via radial artery applanation tonometry. Results: Coronary calcification was present in 38.6% of patients and was associated with age and prior cardiovascular disease on multivariate analyses. The median coronary calcium score in black patients was 0 (IQR 0) and 66 in non‐Blacks (IQR 383, P < 0.001); controls had a coronary calcium score of 0 (IQR 0). Black race remained a significant negative predictor for coronary calcification after adjustment, prevalence ratio = 0.14 and 95% confidence interval (CI): 0.0–0.53. Vascular calcification was not associated with any ambulatory blood pressure parameter. Using receiver operator characteristic curves, an abdominal aorta calcification score of ≥1 showed an area under the curve of 0.83 to predict a coronary calcium score ≥ 10. Conclusion: Black race appears to protect from vascular calcification in South African CKD‐5D patients and this warrants further study regarding the underlying mechanism. The abdominal X‐ray is a useful screening tool for coronary calcification.     

Close association of Chlamydia pneumoniae IgA seropositivity by ELISA with the presence of coronary artery stenosis in haemodialysis patients.

BACKGROUND: Traditional risk factors of cardiovascular disease do not fully explain the accelerated atherosclerosis present in patients with end-stage renal disease (ESRD). The goal of this study was to identify the association of clinical and laboratory factors including seropositivity for Chlamydia pneumoniae determined by a specific enzyme-linked immunosorbent assay (ELISA) with the presence of coronary artery disease identified by coronary angiography in ESRD patients. METHODS: We prospectively enrolled 161 consecutive ESRD patients undergoing haemodialysis for >6 months (106 men, 55 women; mean age 63.1+/-10.2 years; mean dialysis duration 91.3+/-90.1 months). All patients underwent coronary angiography within 1 week after blood sampling. The associations of coronary artery disease with clinical parameters including C. pneumoniae IgA and IgG seropositivity were analysed using multiple logistic regression models. RESULTS: Coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C. pneumoniae IgA was found in patients with coronary stenosis (77 out of 102, 75.5%) more frequently (P<0.001) than in patients without coronary stenosis (10 out of 59, 16.9%). Seropositivity for C. pneumoniae IgA but not IgG was strongly associated with the presence of coronary stenosis in multiple logistic regression analysis (odds ratio, 18.440; 95% confidence interval, 7.500-45.337), independently of the Framingham coronary risk factors, factors peculiar to ESRD or serum C-reactive protein levels. CONCLUSIONS: C. pneumoniae IgA seropositivity determined by ELISA is an independent laboratory factor indicating the presence of coronary artery stenosis in ESRD patients undergoing maintenance haemodialysis.     

Elevated concentrations of cardiac troponins are associated with severe coronary artery calcification in asymptomatic haemodialysis patients.

BACKGROUND: Elevated concentrations of cardiac biomarkers, such as troponins and natriuretic peptides, have been shown to be predictive of poorer long-term cardiovascular outcomes in stable patients with end-stage renal disease (ESRD). However, little is known about the relationship between elevated concentrations of these cardiac markers and underlying coronary artery pathology in these patients. The aim of the present study was to investigate associations between coronary artery calcification (CAC) and the concentrations of cardiac biomarkers in ESRD patients. METHODS: We conducted a cross-sectional study of 38 asymptomatic patients (median age, 54 years; 26 males, 12 females; diabetic, 39%) who were undergoing chronic haemodialysis. In these patients, pre-dialysis circulating concentrations of cardiac troponin T (cTnT), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were measured. We quantified the level of CAC by multirow spiral computed tomography to obtain a CAC score. CAC scores > or = 400 were defined as being indicative of severe CAC. RESULTS: Severe CAC was detected in 17 patients (45%). The degree of CAC severity was positively associated (P < 0.05) with cTnT concentrations. Thus, 15% of patients had severe CAC in the lowest tertile of cTnT, 50% had severe CAC in the middle third, and 69% in the highest third. Similarly, the degree of severity of CAC was positively associated (P < 0.01) with cTnI concentrations across concentration categories. In contrast, there was no association between the degree of CAC severity and the concentrations of either BNP or CK-MB. A logistic regression analysis revealed that elevated concentrations of cTnT (> or = median vs or = 0.1 ng/ml vs 相似文献   

Bilateral internal thoracic artery use for dialysis patients: does it increase operative risk?

BACKGROUND: The efficacy and risk of using the bilateral internal thoracic artery (BITA) for coronary artery bypass grafting in dialysis patients is virtually unknown. METHODS: Twenty-five patients on dialysis who underwent coronary artery bypass grafting using the BITA were retrospectively studied (BITA group). For comparison purposes, 52 patients on dialysis who underwent coronary artery bypass grafting using the left ITA were selected (LITA group). RESULTS: No wound healing problems occurred in the BITA group. Mean postoperative bleeding volume was 1,427 +/- 808 mL and 800 +/- 508 mL in the BITA and LITA groups, respectively (p = 0.00009). Blood transfusions for the BITA and LITA groups required an average of 6.8 and 6.2 units of packed red blood cells, respectively, with no significant difference. Five patients in the BITA group (20%) showed severe atherosclerotic deterioration of the ascending aorta, precluding clamping. Hospital mortality was 4% (1 of 25 patients) in the BITA group and 7.7% (4 of 52 patients) in the LITA group, with no significant difference (p = 0.49). CONCLUSIONS: In patients on dialysis, especially those with severe atherosclerotic or calcified deterioration of the ascending aorta, coronary artery bypass grafting using BITA grafting (arterial in situ conduits) may offer the easiest and most suitable solution without increased operative risk.     

Serum levels of calcification inhibition proteins and coronary artery calcium score: comparison between transplantation and dialysis

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 +/- 12 years; 30 males, 21 females; previous D duration 4.8 +/- 4.2 years; Tx since 6.6 +/- 5.5 years; Cr 1.8 +/- 0.6 mg/dl) and in 49 D patients (age 49 +/- 14 years; 30 males,19 females; D duration 5.6 +/- 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 +/- 1,637 vs. 1,311 +/- 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: r(s) = 0.439, p < 0.001, and r(s) = 0.510, p < 0.0001; D: r(s) = 0.471, p < 0.001, and r(s) = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (r(s) = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (r(s) = -0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (r(m) = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (r(m) = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.