Coronary artery calcification and aortic pulse wave velocity in chronic kidney disease patients

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk of cardiovascular mortality and morbidity. Many complications arise in ESRD patients as a result of the twin arterial pathologies of atherosclerosis and arteriosclerosis. Part of this latter process is calcification of the arterial media, which is thought significantly to increase vascular stiffness. The aim of our study was to explore the relationship between measures of arterial stiffness-pulse wave velocity (PWV)-and the extent of calcification in the coronary arteries (CAC). METHODS: Over a period of 2 years 82 patients from our renal unit were invited to participate in our study. Sixty-two patients agreed to undergo electron beam computerized tomography (EBCT), and in 55 (38 males and 17 females), PWV measurements were made. EBCT and PWV measurements were done according to previously described protocols. RESULTS: The mean age of the 55 patients was 56.4 years. The mean duration of dialysis was 65.4 months, and the mean CAC score was 2551. The mean PWV was 9.13 m/s. PWV strongly correlated with total CAC even after correction for age, dialysis duration, and time averaged C-reactive protein (CRP) (P= 0.0001). CAC scores were significantly different when compared according to PWV tertiles (P= 0.0001). CONCLUSION: We have demonstrated that PWV is strongly related to the degree of EBCT-derived coronary artery calcium score in chronic kidney disease patients.     

Tight relations between coronary calcification and atherosclerotic lesions in the carotid artery in chronic dialysis patients

Aim: Both vascular calcification and atherosclerosis are highly prevalent in patients with end‐stage renal disease (ESRD) and have been associated with increased cardiovascular morbidity. Because those two phenomena might be only coincidentally related in chronic haemodialysis (HD) patients, in this study, coronary artery calcification (CAC), common carotid artery intima media thickness (CCA‐IMT) and thickness of atherosclerotic plaques in the carotid artery were simultaneously measured. Methods: In a cross‐sectional study of 47 HD patients (31 male, mean age 56.8 ± 11.4 years, and 16 female, mean age 56.0 ± 7.5 years) without history of major cardiovascular complications. CCA‐IMT and presence and thickness of atherosclerotic plaques were measured with ultrasound and CAC with multidetector computed tomography. Results: The CAC were present in 70.2% of patients. The mean CAC was 1055 ± 232, the mean CCA‐IMT was 0.96 ± 0.21. The atherosclerotic plaques in the common carotid arteries were visualized in 38 patients (80.1%), the mean thickness of the atherosclerotic plaque was 1.61 ± 0.8 mm. We found a significant positive correlation between CAC and CCA‐IMT (r = 0.70, P < 0.001). The thickness of atherosclerosis plaque positively correlated with CAC as well as with CCA‐IMT (r = 0.60, P < 0.001 and r = 0.7, P < 0.003, respectively). Conclusion: The study revealed close relationships between CAC, intima media thickness and the thickness of atherosclerotic plaques in dialysis patients. It may indicate that both vascular calcification and atherosclerotic lesions frequently coexist in patients with ESRD and that the intima media thickness could serve as a surrogate marker of vascular calcification.     

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.     

Screening for silent ischemia with coronary artery calcium and nuclear stress testing in nondiabetic patients prior to kidney transplant

Whether coronary artery calcium (CAC) screening in pretransplant patients may help predict silent myocardial ischemia is unknown. Accordingly, we performed CAC imaging on 46 nondiabetic patients awaiting kidneytransplant. All patients underwent multidetector computed tomography imaging for CAC quantification, and a vasodilator myocardial perfusion stress (MPS) test was performed only in patients with a total CAC score>300 or>100 in a single coronary artery. The mean patient's age was 46+/-14 years and the median dialysis vintage was 33 months (interquartile range 19-53). The median CAC score was 82 (interquartile range 0-700) and correlated with patients' age (p=0.006) and dialysis vintage (p=0.02). Nineteen patients qualified for MPS, but 5 refused the test. Of the remaining 14 patients, 7 patients had normal scans and 7 showed a minimal perfusion defect in the inferoposterior segment of the left ventricle. At the time of writing, 12 patients have undergone successful kidney transplantation without untoward complications. CAC screening does not appear to be associated with silent ischemia in pretransplant patients. Though CAC is extensive in dialysis patients, calcium may be associated with nonobstructive atherosclerotic lesions or calcification of the media layer of the vessel wall.     

Determinants of coronary artery calcification in diabetics with and without nephropathy

BACKGROUND: In the general population, including those with diabetes mellitus, coronary artery calcification (CAC) correlates with atherosclerotic plaque burden. On the other hand, accumulating evidence suggests that disordered mineral metabolism significantly contributes to the vascular calcification in individuals with end-stage renal disease (ESRD). METHODS: In order to determine the relative contribution of accelerated atherosclerosis and disordered mineral metabolism to CAC in chronic kidney disease, a pilot study of 90 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N= 30; diabetic nephropathy (DN), N= 60]. RESULTS: CAC was more prevalent and severe among individuals with DN compared to diabetic controls (odds ratio for prevalence 8.1, 95% CI 2.3-28.5; median scores, 66 vs. 4, P < 0.001). None of the 4 measures of disordered mineral metabolism evaluated in this study (serum calcium, phosphorus, parathyroid hormone, and 1,25 di-hydroxy vitamin D levels) correlated with the prevalence or severity of CAC, or accounted for the differences seen between DN and diabetic controls. On the other hand, the difference in the severity of hypertension (number of antihypertensive medications) appeared to account for the differences in CAC burden seen between DN and diabetic controls. CONCLUSION: This first such study of nondialyzed individuals with DN suggests that, unlike ESRD patients, the high CAC burden seen at earlier stages of diabetic chronic kidney disease is probably unrelated to disordered mineral metabolism. The relationship between the severity of hypertension and CAC burden provides a probable target for intervention in the predialysis phase of DN.     

Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: the Framingham Heart Study

BACKGROUND: Among patients with end-stage renal disease (ESRD), the risk of cardiovascular disease is 10 to 20 times higher than the general population. Adults with ESRD have increased coronary-artery calcification (CAC) detected by electron-beam computed tomography (EBCT). Because the risk of coronary heart disease is increased even at moderate declines in kidney function, we sought to test whether high CAC scores are seen among those with mild reductions in kidney function. METHODS: Men and women free of symptomatic cardiovascular disease underwent EBCT. Coronary calcium was quantified using the method described by Agatston. Renal function was estimated by glomerular filtration rate (GFR). Spearman correlation coefficients were used to test the association between GFR and CAC. RESULTS: Three hundred nineteen subjects (162 men/157 women), mean age 60, were included. Mean GFR was 86 +/- 23 mL/min/1.73 m2 (range 31-169; 10% with GFR <60 mL/min/1.73 m2). The median CAC scores by quartile of GFR were 85.9, 48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28 (P < 0.0001). This remained significant after adjustment for age and sex (-0.11, P < 0.05), and additionally after adjustment for body mass index (-0.11, P < 0.05), hypertension (-0.11, P < 0.05), or total cholesterol (-0.12, P= 0.04). A similar correlation was noted after multivariable adjustment (-0.10, P < 0.08). CONCLUSION: Mild declines in kidney function are associated with subclinical coronary artery calcification in a sample of subjects free of clinically apparent cardiovascular disease. This might help explain the increased risk of cardiovascular disease among individuals with renal dysfunction. Larger ongoing studies are needed to better quantify this finding.     

终末期肾病患者心血管事件与血清胎球蛋白A及冠脉钙化的关系

目的探讨终末期肾病（ESRD）患者心血管事件发生与血清胎球蛋白A及冠脉钙化的关系。方法对38例ESRD初始血液透析患者进行血清胎球蛋白A及相关因素检测，对其中的29例患者进行冠状动脉多层螺旋CT钙化评价研究。所有38例患者随访时间为18个月。22例非ESRD慢性肾脏病（CKDⅡ～Ⅲ期）患者人选对照组。结果38例ESRD初始透析患者在18个月随访期内出现心血管事件30例次，因心血管事件死亡者6例，占15．79％，而非ESRD患者心血管事件仅3例次（P〈0．01）且无一例死亡（P〈0．05）。ESRD血清低胎球蛋白A组心血管事件显著高于ESRD血清高胎球蛋白A组（P〈0．01）。多元逐步回归分析显示，心血管事件与血清胎球蛋白A（P〈0．01）、C反应蛋白（CRP）（P=0．0014）及低密度脂蛋白C（LDL-C）（P=0．008）密切相关。18／29例（62．07％）有冠状动脉钙化。冠状动脉钙化患者心血管事件比无冠状动脉钙化患者显著增多（P〈0．01）。冠脉钙化的ESRD患者血清胎球蛋白A水平较无冠脉钙化的ESRD患者明显下降（P〈0．01）。冠脉钙化与胎球蛋白A下降及高血磷有关（P〈0．01，P〈0．01）。结论ESRD透析患者心血管事件和（或）心血管事件死亡可能与血清胎球蛋白A下降及冠状动脉钙化有关。     

Angiographic progression of coronary artery disease in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have an increased risk of developing coronary artery disease (CAD). The cardiovascular mortality of dialysis patients is 10-15 times higher compared with the general population. The aim of our study was to evaluate the morphological progression of coronary arteriosclerosis in this cardiovascular high-risk group by visual assessment and quantitative coronary angiography. Methods and results. In 26 patients with chronic renal failure (age, 47+/-11 years; 15 male; duration of dialysis, 23+/-25 months) the severity of CAD and degree of coronary stenoses were assessed in two coronary angiograms after a mean follow-up interval of 30+/-15 months (12-60). Baseline angiography revealed CAD in 13/22 patients (59%). The second angiography was performed as screening procedure prior to renal transplantation (n=20) and/or as follow-up angiography after coronary angioplasty (n=10). Visual assessment showed a progression defined by the development of haemodynamically relevant stenosis of >50% luminal diameter in 13 patients. Quantitative angiographic evaluation was performed in a total of 45 segments showing >25% narrowing at the second angiogram. A progression (>15% luminal reduction) was found in 17 of 45 segments, a new lesion (initial luminal diameter <20%) was detected in nine segments, resulting in progression or new lesion in 16 patients (62%). Patients with or without progression did not differ in age, duration of dialysis treatment, number of cardiovascular risk factors, or serum total cholesterol and fibrinogen levels. After percutaneous transluminal coronary angioplasty (PTCA) a restenosis was seen in seven of 16 primarily successfully dilated segments. After the second angiography, myocardial revascularization was performed in eight patients (1 PTCA, 7 coronary artery bypass graft). CONCLUSIONS: Patients with end-stage renal disease have a high prevalence of CAD. In line with the clinical course, CAD patients on maintenance dialysis undergo rapid angiographic progression of CAD, which results in a high rate of subsequent myocardial revascularizations.     

终末期肾脏病透析患者骨密度与冠脉钙化的相关性分析

目的探讨终末期肾脏病(end stage renal disease,ESRD)透析患者骨密度与冠状动脉钙化(coronary artery colcification,CAC)之间的相关性。方法本研究为横断面研究。纳入115例ESRD患者,收集相关人口学特征、原发病、实验室检查等资料,双能X射线评估腰椎、股骨颈及髋部骨密度,多层螺旋计算机断层扫描(MSCT)检查患者CAC发生情况。以钙化积分100为界,将患者分为高钙化组和低钙化组。结果高钙化组56例,占维持性透析患者48%,其中男性36例,占高钙化组人数64.3%。高钙化组年龄、透析龄及血清甲状旁腺激素、碱性磷酸酶、25(OH) D水平均明显高于低钙化组,而股骨颈骨密度、髋部骨密度、血清胆固醇水平明显低于低钙化组(P0.05);男性高钙化组股骨颈骨密度及髋部骨密度明显低于低钙化组,且其冠脉钙化积分与股骨颈骨密度(r=-0.34,P0.05)、髋部骨密度(r=-0.65,P0.01)呈负相关。多元线性回归分析校正了年龄、透析龄等因素后仍显示男性髋部骨密度与冠脉钙化积分呈负相关(β=-1870.47,P0.05)。但在女性患者中,高钙化组与低钙化组骨密度无明显差异。结论骨密度降低可能是男性维持性透析患者冠脉钙化风险增高的危险因素。     

Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients

BACKGROUND: Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). METHODS AND RESULTS: 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding the percentage luminal reduction of the most severe lesion in each artery. Patients with normal angiograms had significantly less arterial stiffness (as reflected by both a lower PWV=8.42+/-1.53 m/s and a lower AIx=17.9+/-5.55 %) compared with the 35 subjects with evidence of obstructive coronary disease at angiography (PWV=9.21+/-1.15 m/s and AIx=23.4+/-5.4 %, P<0.05 for both). Moreover, as more coronary vessels were affected, PWV and AIx increased proportionally. Based on receiver operating characteristics (ROC) curve analysis mean PWV levels showed an optimal cut-off point at 8.35 m/s (sensitivity=0.77; specificity=0.60), while mean AIx levels showed an optimal cut-off point at 17% (sensitivity=0.87; specificity=0.70). There was a statistically significant linear relationship between the atherosclerosis burden and both measures of arterial stiffness: PWV (r=0.31, p=0.007) and AIx (r=0.46, p=0.003). Independent predictors for the arterial stiffness parameters in this CKD population (multiple stepwise regression analysis) were age (r=0.69 for PWV and r=0.62 for AIx), and mean arterial pressure (MAP) (for AIx, p<0.0001). CONCLUSION: This study provides the first direct evidence in a cross-sectional investigation that PWV and AIx are related to the extent of coronary obstruction in CKD patients.     

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   

Pulse wave velocity--a useful tool for cardiovascular surveillance in pre-dialysis patients.

BACKGROUND: Cardiovascular mortality is high among patients with chronic kidney disease. Pulse wave velocity (PWV) is a simple method used for arterial distensibility evaluation. Few data are available concerning PWV in pre-dialysis patients. The aim of this study was to evaluate the association between PWV and cardiovascular disease in pre-dialysis. METHODS: One hundred and four patients were submitted to PWV analysis, coronary artery calcium (CAC) determination with a multi-slice CT scan of the coronary arteries, echocardiogram and a carotid intima-media thickness (IMT) evaluation, with a high resolution ultrasound. The demographic characteristics and laboratory tests results were studied. RESULTS: The mean age of those studied was 54.4 +/- 11.5 years, 60% were males and the mean creatinine clearance was 40 ml/min/1.73 m(2). The mean PWV was 12.2 +/- 3.4 m/s and it was significantly higher in males, diabetics, those with creatinine clearance <60 ml/min and proteinuria > or =1 g/24 h. PWV was correlated with systolic blood pressure, age, triglycerides, total cholesterol and 24 h proteinuria. In the multiple regression analysis, PWV was significantly associated with diabetes, age, systolic blood pressure and cholesterol. Fifty-eight patients (56%) presented coronary calcification and PWV correlated with coronary calcium score (R = 0.48; P < 0.001) and calcium volume (R = 0.50; P < 0.001). Moreover, PWV was higher in patients with coronary calcification (13.4 +/- 3.6 m/s vs 10.7 +/- 2.4 m/s; P < 0.001). The mean left ventricular mass index (LVMI) was 106 +/- 31 g/m(2) and 24% of patients had left ventricular hypertrophy, while 19 (18.3%) patients had left ventricular dysfunction. PVW was correlated with LVMI (R = 0.25; P = 0.01) while no association could be seen between PWV and the ejection fraction or left ventricular dysfunction. A correlation between the IMT and PWV was observed (R = 0.27; P = 0.005). In addition, those with a thicker IMT had a higher PWV (13.2 +/- 3.4 m/s vs 11. 2 +/- 3.2 m/s; P = 0.003). CONCLUSION: PWV is associated with cardiovascular disease in pre-dialysis patients and can be a useful tool to identify patients with increased cardiovascular risk.     

Assessment of vascular calcification in ESRD patients using spiral CT.

BACKGROUND: Dialysis patients have increased vascular calcification of the coronary arteries and aorta by electron beam CT scan. The purpose of the present study was to utilize an alternative machine, spiral CT, to assess calcification in end-stage renal disease (ESRD) patients. METHODS: Two groups of patients with ESRD were evaluated: group 1, those receiving a renal transplant (n=38); and group 2, those remaining on dialysis (n=33). All patients underwent quad-slice spiral CT with retrospective gating to evaluate coronary artery and aorta calcification scores. Both area (Agatston method) and volume calculations were utilized, with retrospective gating in all but 16 subjects. Laboratory tests, medications and clinical characteristics were analysed. RESULTS: Using spiral CT, the intra-reader variability for coronary artery calcification (after correction for very low scores) was 0.9% mean / 0% median using the area (Agatston method) and 2.9% mean / 0% median using volume calculations. Group 1 patients were younger, more likely to be Caucasian and on peritoneal dialysis, had lower serum calcium and higher C-reactive protein levels than group 2. In patients without vs those with coronary artery calcification, only longer duration of dialysis (34+/-64 vs 55+/-50 months, P=0.004; r=0.39, P=0.005) and increasing age (39+/-13 vs 54+/-10 years, P<0.001; r=0.29, P=0.039) were associated, whereas only increasing age was associated with aorta calcification. CONCLUSION: In ESRD patients, the factors correlating with coronary calcification were duration of dialysis and advancing age, whereas only age correlated with aorta calcification. Spiral CT offers an alternative technique for the assessment of these changes.     

Relationship between serum magnesium level and coronary artery calcification in maintenance hemodialysis patients

Objective To evaluate the relationship between serum magnesium and coronary artery calcification (CAC) and their associated factors. Methods 131 patients with chronic kidney disease on regular hemodialysis (HD) were recruited into this study from December 2014 to December 2015 in our center. Demographic and clinical data of selected patients were collected. Serum fibroblast growth factor 23 (FGF-23) level was quantified by enzyme linked immunosorbent assay(ELISA). Quantification of coronary artery calcification score (CACs) was determined by multi-slice spiral computed tomography (MSCT). The relationships between serum magnesium and FGF-23 level, CACs, demographic and clinical data were investigated. Results Patients were divided into low serum magnesium group, normal serum magnesium group and high serum magnesium group according to their serum magnesium levels. There were significant differences in the distribution of diabetes history, serum phosphorus, serum albumin, serum pre albumin, serum uric acid among these three groups(P＜0.05). A significant positive correlation was confirmed between serum magnesium level and serum albumin, serum pre albumin, serum phosphorus and serum uric acid by Pearson correlation analysis and Spearman correlation analysis (r=0.389, 0.234, 0.200, 0.234, P=0.000, 0.007, 0.022, 0.007, respectively). According to the degree of CAC, all maintenance hemodialysis (MHD) patients were divided into non-calcification group, low calcification group, moderate calcification group and high calcification group, and there were significant differences in the distribution of the age, serum phosphorus, serum magnesium, FGF-23 levels among these groups (P＜0.05) . Spearman correlation analysis showed that CACs was positively correlated with age, FGF-23, serum phosphorus (r=0.309, 0.277, 0.180, P=0.000, 0.001, 0.040, respectively), while negatively correlated with serum magnesium level (r=-0.238, P=0.006) in patients with MHD. The independent risk factors of CACs were aging, high level of FGF-23 in MHD patients by using ordinal logistic regression. However, Hypermagnesemia was a protective factor. Conclusions The history of diabetes, low serum albumin, phosphorus metabolism disorder and CAC are associated with hypomagnesemia in MHD patients. In MHD patients, aging as well as high level of FGF-23 are the risk factors of CAC, and hypermagnesemia is a protective factor of CAC.     

Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis

Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6-388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes.     

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.     

Familial aggregation of coronary artery calcium in families with type 2 diabetes

Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P = 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.     

Increased incidence of radial artery calcification in patients with diabetes mellitus.

BACKGROUND: The radial artery (RA) has become a popular conduit for coronary artery bypass (CAB). Preoperative RA evaluation in CAB patients has focused on ulnar collateral circulation to the hand and not on the conduit itself, yet the RA is prone to atherosclerosis and perhaps calcification, particularly in patients with diabetes mellitus (DM). We sought to determine the incidence of RA calcific disease in diabetic vs nondiabetic patients using ultrasonography to establish its role in preoperative evaluation of CAB patients. METHODS: Ultrasound images of the RA were obtained in 102 men (49 with DM) referred to a vascular laboratory. For each patient, a RA calcification index (CI; 0-4) was derived from separate scores accounting for calcification density, longitudinal vessel involvement, and bilaterality. Differences between diabetic and nondiabetic patients were determined by unpaired t test. RESULTS: Mean (+/-SEM) CI was greater in diabetic patients vs nondiabetics (2.32 +/- 0.21 vs 1.17 +/- 0.20; P < 0.0001), due mainly to an increase in dense calcification, which was observed in 17 (34%) diabetics vs 5 (9.6%) nondiabetics (P = 0.007). Calcifications were completely absent in 27 (52%) nondiabetics vs 9 (18%) diabetics (P = 0.000). CONCLUSIONS: These data indicate that both the incidence and the severity of RA calcific disease are increased by DM. Preoperative imaging of the RA should be considered in diabetic CAB candidates and perhaps in nondiabetics with multiple risk factors to avoid unnecessary forearm exploration or inadvertent use of a diseased conduit.     

Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis.

BACKGROUND: Coronary artery calcification (CAC) is an extensive and common complication in patients with end-stage renal disease (ESRD). The aim of this study was to assess prospectively the change in CAC over a 2-year period and to identify the factors that may be associated with CAC progression in ESRD patients. METHODS: The final analysis was performed on 40 of 43 stable haemodialysis patients who initially entered into the study. The study population underwent multirow spiral computed tomography to derive CAC scores at baseline and after a minimum of 12 months (24 months in 30 patients, 18 months in four, and 12 months in the remaining six patients). To provide a stable estimate that was unbiased with respect to the baseline CAC, square root-transformed CAC scores were used for the analyses of the changes in CAC. RESULTS: The median CAC score was 191 (range, 0-2403) mm3 at baseline and increased to 253 (range, 0-2745) mm3 at follow-up (P < 0.001) and the median annualized change in square root-transformed CAC score was 1.48 (range, -0.95-8.64) mm3/year. The annualized change of the square root-transformed CAC score positively correlated with the time-integrated levels of C-reactive protein (R = 0.521, P = 0.001), phosphorus (R = 0.433, P = 0.005) and calcium x phosphorus product (R = 0.394, P = 0.012), but did not correlate with the levels of fetuin-A or lipid parameters. Even after adjusting for age, gender and baseline CAC score, C-reactive protein levels were independently associated with CAC progression. CONCLUSION: These data suggest that chronic inflammation as well as altered mineral metabolism contributes to a rapid progression of CAC in ESRD patients. Additional, larger scale studies are required to confirm our findings.