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.     

Progression of coronary artery calcification in diabetics with and without chronic kidney disease

BACKGROUND: Rapid progression of coronary artery calcification (CAC) has been reported among individuals with end-stage renal disease (ESRD). There is limited information on the progression of CAC during earlier stages of diabetic chronic kidney disease (CKD). METHODS: In a prospective, cohort study of type 2 diabetic individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an average interval of 19 months. All scan images were acquired at end-systole to minimize interscan variability. In order to eliminate the dependence of the residual error from interscan variability on baseline CAC scores, square root transformed CAC scores were used for analyses of progression of coronary calcification. RESULTS: Repeat EBCT scans were completed in 68 subjects (diabetic controls: 23; DN: 45). There was a highly significant relationship between the proportion of subjects with progressive CAC and renal disease-DN who progressed to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P < 0.001). Similarly, the magnitude of change was significantly related to renal disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic controls, P < 0.001). Using logistic regression and controlling for non-dialyzed DN, ESRD and inter-scan interval, advanced age was the only significant variable associated with progression of CAC. Finally, serum creatinine and baseline CAC score emerged as independent predictors for the magnitude of increase in CAC. CONCLUSION: Progression of CAC is apparent among individuals with DN both before and after ESRD. However, the risk factors associated with progression of CAC may differ at different stages of CKD.     

Prevalence, severity and predictors of HOMA-estimated insulin resistance in diabetic and nondiabetic patients with end-stage renal disease

BACKGROUND: Prevalence of insulin resistance (IR) is increased in type 2 diabetes and in end-stage renal disease (ESRD). IR is associated with advanced atherosclerosis and is an independent predictor for cardiovascular disease in diabetes and ESRD patients. We investigated prevalence, severity, predictors and relation to vascular diseases by the homeostasis model assessment (HOMA-IR) in diabetic and nondiabetic ESRD patients. METHODS: ESRD patients with type 2 diabetes (n = 27) and nondiabetic ESRD patients (n = 35) were included in the study. IR was assessed with the HOMA-IR using fasting glucose and insulin levels. Additionally, serum levels of C-peptide, HbA1c, triglycerides, cholesterol and C-reactive protein and blood pressure were assessed. RESULTS: Median HOMA-IR was significantly higher in the diabetic ESRD patients than in the nondiabetic ESRD patients (6.3 [range 0.7-61.7] vs. 2.4 [range 0.3-5.7]; p < 0.001). Systolic blood pressure and triglycerides were significantly higher in patients with higher HOMA-IR, whereas HDL cholesterol was significantly lower in those patients. Only nondiabetic patients with increased HOMA-IR had significantly higher C-peptide levels than those with lower HOMA-IR (14.9 + 5.7 vs. 9.0 + 4.3, p = 0.004). Vascular disease prevalence was significantly higher in diabetic patients with higher HOMA-IR than in those with lower HOMA-IR. CONCLUSIONS: Prevalence and severity of HOMA-IR was greater in diabetic ESRD patients than in those without diabetes. In diabetic patients low HDL cholesterol was the only predictor for higher HOMA-IR, whereas in nondiabetic patients a high C-peptide level was the only predictor for higher HOMA-IR. The prevalence of vascular diseases is associated with higher HOMA-IR in ESRD patients.     

Cardiovascular calcification in Hispanic Americans (HA) with chronic kidney disease (CKD) due to type 2 diabetes

BACKGROUND: Cardiovascular calcification (CVC) is common and severe in patients with end-stage renal disease on dialysis. However, the prevalence and severity of CVC is less well documented in patients with chronic kidney disease (CKD) not yet on dialysis. METHODS: Fifty-eight nondialyzed HA with type 2 diabetes and CKD were enrolled. They comprise 29 patients with stages 1 and 2 CKD (early CKD group) and 26 patients with stages 4 and 5 CKD (advanced CKD group). Coronary artery calcification (CAC) was measured by ultrafast spiral computed tomography, while peripheral artery calcification (PAC) was evaluated by plain x-ray of the chest, pelvis, thighs, and lower extremities. RESULTS: The prevalence of CAC and PAC were significantly higher in the advanced CKD group compared to the early CKD group (73% vs. 38%; P < 0.01 and 85% vs. 35%; P < 0.0001, respectively). The median CAC scores were 18-fold greater in the advanced CKD group (138.9 vs. 7.8, respectively). By linear regression analysis, a strong association was found between the level of renal function and ln total volume of CAC. CONCLUSION: Our data indicate that CAC and PAC are common and severe in HA diabetic patients with CKD not previously treated with dialysis, calcium-based phosphate binders, or vitamin D analogues. Lower level of renal function is associated with increased burden of vascular calcification in predialysis patients with CKD.     

Epicardial Adipose Tissue and Coronary Artery Calcification in Diabetic and Nondiabetic End-Stage Renal Disease Patients

Background/aims: Atherosclerosis, coronary artery calcification, diabetes mellitus, inflammation, endothelial dysfunction, and left ventricular hypertrophy are the most commonly encountered risk factors in the pathogenesis of cardiovascular disease in end-stage renal disease (ESRD) patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between coronary artery disease (CAD) and EAT was shown in healthy subjects and patients with high risk of CAD. To date, there is not enough data about EAT in diabetic and nondiabetic ESRD patients. Therefore, we aimed to investigate the EAT and coronary artery calcification score (CACS) in diabetic and nondiabetic ESRD patients and healthy subjects. Methods: Sixty ESRD patients (17 diabetic, 43 nondiabetic ESRD patients) and 20 healthy subjects were enrolled in the study. EAT and CACS were performed by a 64-slice multidetector computed tomography scanner. Results: There were no differences in age, gender, body mass index, predialysis systolic and diastolic blood pressure levels, biochemical parameters including serum low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, and C-reactive protein between healthy subjects, diabetic, and nondiabetic ESRD patients. Total CACSs and EAT measurements were significantly higher in diabetic ESRD patients when compared with nondiabetic ESRD patients and healthy subjects. There was statistically significant relationship between EAT and CACS in ESRD patients (p < 0.0001, r = 0.48). Conclusion: In conclusion, we found a significant increase in terms of EAT and CACS in diabetic ESRD patients when compared with nondiabetic ESRD patients and healthy subjects.     

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.     

Different risk factors for vascular calcification in end-stage renal disease between diabetics and nondiabetics: the respective importance of glycemic and phosphate control

Vascular calcification is highly prevalent in dialysis patients, and significantly increases cardiovascular mortality. The presence and progression of vascular calcification is significantly associated with chronic inflammation and malnutrition. Disorders of mineral metabolism, particularly hyperphosphatemia, have been emphasized as risk factors for vascular calcification. Although vascular calcification has been reported to be highly prevalent in diabetic patients with end-stage renal disease (ESRD), the risk factors for vascular calcification in these patients have not been fully explored. Through a review of the literature and our recent studies examining vascular calcification in ESRD patients, hyperphosphatemia is significantly associated with vascular calcification in nondiabetic ESRD patients, while it may not be a significant risk factor for vascular calcification in diabetic ESRD patients. In diabetic patients, vascular calcification occurs long before the initiation of dialysis therapy, and the factors associated with vascular calcification in non-uremic diabetics appear to be hyperglycemia and related metabolic disorders, such as increased glycation and oxidative stress. In diabetic ESRD patients, hyperglycemia is also suggested to be a significant factor associated with the progression of vascular calcification. Thus, the importance of glycemic and phosphate control is suggested to be emphasized in diabetic and nondiabetic ESRD patients, respectively, for prevention of the progression of vascular calcification.     

Cardiovascular calcification in nondialyzed patients with chronic kidney disease

Chronic kidney disease (CKD) has become a major health-care problem of global proportions. Progression to end-stage renal disease (ESRD), the need for renal replacement therapy, and the high annual death rate of dialysis patients are the most noticeable outcomes of CKD. Less appreciated, however, is the fact that most patients with CKD actually die mainly from cardiovascular disease, rather than progress to ESRD. Coronary artery calcification (CAC), a surrogate marker of atherosclerosis, is common in dialysis and CKD patients. Coronary artery calcium scores, as measured by ultrafast computed tomography, is an independent predictor of future cardiac events. Using this technique, several studies have documented extensive calcification in dialysis patients, a subject of several exhaustive reviews. Unfortunately, much less attention has been paid to calcification in nondialyzed patients with CKD. In this review, I will emphasize the fact that CVC is common in patients with CKD not yet on dialysis, develops early in the course of CKD, and worsens with the decline in renal function particularly among diabetics who progressed to ESRD. I will also discuss the pathogenesis of CVC in CKD patients and highlight the lack of a major role for abnormalities of mineral metabolism in the pathogenesis of calcification in CKD patients. In addition to the high prevalence of traditional risk factors for CAD, the presence of proteinuria, reduced renal function, diabetic nephropathy, and the rate of progression to ESRD may represent the main uremia-related factors that increase the risk for calcification in CKD. Finally, I will review the protective role of inhibitors of calcification in CKD.     

Coronary artery disease among diabetic and non-diabetic patients with end stage renal disease.

Cardiovascular disease is the major cause of death among patients with end stage renal disease and accounts for about half the deaths among the dialysis population. Several researchers have reported a high prevalence of coronary artery disease among diabetic patients with renal failure and coronary arteriography is often considered an integral part of the pre-transplant evaluation of diabetic patients with end stage renal disease. However, very few reports have addressed the question of coronary disease in non-diabetic patients, and the pattern and prevalence of coronary artery disease in non-diabetic patients with end stage renal disease are not well defined. We evaluated the clinical and coronary angiographic findings in 158 consecutive patients (84 diabetic and 74 non-diabetic) with end stage renal disease. The coronary arteries were divided into 16 segments and each segment was analyzed for the presence of coronary disease, which was defined as the presence of > or = 50% luminal diameter stenosis. Diabetic patients had more adverse risk factors for coronary artery disease, yet there was no significant difference in the prevalence of coronary artery disease between the diabetic and non-diabetic patients (67% vs. 55%, p = 0.15), or in the number of affected coronary artery segments (2.0 vs. 1.4, p = 0.05). Triple vessel coronary artery disease was however, significantly more common among the diabetic subjects (27% vs. 12%, p = 0.005). Non-diabetic patients with end stage renal disease also have a high prevalence of coronary artery disease and may merit as careful investigation of their coronary status as their diabetic counterparts.     

CORONARY ARTERY DISEASE AMONG DIABETIC AND NON-DIABETIC PATIENTS WITH END STAGE RENAL DISEASE

Cardiovascular disease is the major cause of death among patients with end stage renal disease and accounts for about half the deaths among the dialysis population. Several researchers have reported a high prevalence of coronary artery disease among diabetic patients with renal failure and coronary arteriography is often considered an integral part of the pretransplant evaluation of diabetic patients with end stage renal disease. However, very few reports have addressed the question of coronary disease in non-diabetic patients, and the pattern and prevalence of coronary artery disease in non-diabetic patients with end stage renal disease are not well defined. We evaluated the clinical and coronary angiographic findings in 158 consecutive patients (84 diabetic and 74 non-diabetic) with end stage renal disease. The coronary arteries were divided into 16 segments and each segment was analyzed for the presence of coronary disease, which was defined as the presence of ≥ 50% luminal diameter stenosis. Diabetic patients had more adverse risk factors for coronary artery disease, yet there was no significant difference in the prevalence of coronary artery disease between the diabetic and non-diabetic patients (67% vs. 55%, p = 0.15), or in the number of affected coronary artery segments (2.0 vs. 1.4, p = 0.05). Triple vessel coronary artery disease was however, significantly more common among the diabetic subjects (27% vs. 12%, p = 0.005). Non-diabetic patients with end stage renal disease also have a high prevalence of coronary artery disease and may merit as careful investigation of their coronary status as their diabetic counterparts.     

Propensity case-matched analysis of off-pump coronary artery bypass grafting in patients with atheromatous aortic disease

OBJECTIVE: Atheromatous aortic disease is a risk factor for excessive mortality and stroke in patients undergoing coronary artery bypass grafting. Outcomes of off-pump coronary artery bypass grafting and coronary artery bypass grafting with cardiopulmonary bypass in patients with severe atheromatous aortic disease were compared by propensity case-match methods. METHODS: Routine intraoperative transesophageal echocardiography identified 985 patients undergoing isolated coronary artery bypass grafting with severe atheromatous disease in the aortic arch or ascending aorta. Off-pump coronary artery bypass grafting was performed in 281 patients (28.5%). Propensity matched-pairs analysis was used to match patients undergoing off-pump coronary artery bypass grafting (n = 245) with patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. RESULTS: Univariate analysis revealed decreased hospital mortality (16/245, 6.5% vs 28/245, 11.4%; P =.058) and stroke prevalence (4/245, 1.6% vs 14/245, 5.7%; P =.03) in off-pump coronary artery bypass grafting compared with coronary artery bypass grafting with cardiopulmonary bypass. Freedom from any postoperative complication was higher in off-pump coronary artery bypass grafting compared with coronary artery bypass grafting with cardiopulmonary bypass (226/245, 92.2% vs 196/245, 80.0%; P <.001). Multivariable analysis of preoperative risk factors showed that increased hospital mortality was associated with coronary artery bypass grafting with cardiopulmonary bypass (odds ratio = 2.7; P =.01), fewer grafts (P =.05), acute myocardial infarction (odds ratio = 11.5; P <.001), chronic obstructive pulmonary disease (odds ratio = 2.4; P =.03), previous cardiac surgery (odds ratio = 10.2, P =.05), and peripheral vascular disease (odds ratio = 2.1; P =.05). Cardiopulmonary bypass was the only independent risk factor for stroke (odds ratio = 3.6, P =.03). At 36 months' follow-up, comparable survival was observed in the off-pump coronary artery bypass grafting and coronary artery bypass grafting with cardiopulmonary bypass groups (74% vs 72%). Multivariable analysis revealed that renal disease (P <.001), advanced age (P <.001), previous myocardial infarction (P =.03), and lower number of grafts (P =.02) were independent risks for late mortality. CONCLUSIONS: Patients with severe atherosclerotic aortic disease who undergo off-pump coronary artery bypass grafting have a significantly lower prevalence of hospital mortality, perioperative stroke, and overall complications than matched patients who underwent coronary artery bypass grafting with cardiopulmonary bypass. Routine intraoperative transesophageal echocardiography identifies severe atheromatous aortic disease and directs the choice of surgical technique.     

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.     

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.     

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.     

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.     

Lipid transfer protein activities in type 1 diabetic patients without renal failure and nondiabetic control subjects and their association with coronary artery calcification

This study examined the role of cholesteryl ester transfer (CET), cholesteryl ester transfer protein (CETP) activity, and phospholipid transfer protein (PLTP) activity in the increased prevalence of coronary artery calcification (CAC) in diabetic subjects compared with nondiabetic subjects and in the loss of the sex difference in CAC in diabetes. CETP activity, PLTP activity, and CET were measured in 195 type 1 diabetic subjects without renal failure and 194 nondiabetic control subjects of similar age (30-55 years) and sex distribution (50% female). CAC was quantified with electron beam computed tomography. CETP activity was higher in diabetic subjects (mean 84 arbitrary units [AU]) than in nondiabetic subjects (80 AU, P = 0.028). PLTP activity was also higher in diabetic subjects (96 AU) than in nondiabetic subjects (81 AU, P < 0.001). However, CET was lower in diabetic men (geometric mean 32 nmol. ml(-1).h(-1)) than nondiabetic men (37 nmol.ml(-1).h(-1), P = 0.004) and did not differ between diabetic (30 nmol. ml(-1).h(-1)) and nondiabetic (32 nmol.ml(-1).h(-1), P = 0.3) women. CETP and PLTP activities were not associated with CAC. CET was positively associated with CAC in both diabetic and nondiabetic subjects (odds ratio per 10 nmol.ml(-1).h(-1) increase in CET in all subjects = 1.4, P = 0.001). The prevalence of CAC was similar in diabetic (51%) and nondiabetic (54%, P = 0.7) men but was much higher in diabetic (47%) than nondiabetic (21%, odds ratio 3.6, P < 0.001) women so that there was no sex difference in CAC in diabetic subjects. The odds of CAC in diabetic women compared with nondiabetic women was altered little by adjustment for CETP activity, PLTP activity, or CET (odds ratio on adjustment 3.7, P < 0.001). The greater effect of diabetes on CAC in women than in men, i.e., the loss of the sex difference in CAC, was independent of CETP and PLTP activity and CET. In conclusion, among both diabetic and nondiabetic subjects, higher cholesteryl ester transfer is a risk factor for CAC. However, abnormalities in cholesteryl ester transfer or lipid transfer protein activities do not underlie the increased CAC risk in diabetic women compared with nondiabetic women or the loss of the sex difference in CAC in diabetes.     

Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study

Valvular calcification is common in the setting of end-stage kidney disease and is associated with increased risks for cardiovascular disease events. It is unknown whether the prevalence of valvular calcification is increased in milder kidney disease after accounting for cardiovascular risk factors. Participants who attended the sixth examination of the Framingham Offspring Study (1995 to 1998) were eligible. Kidney function was estimated by GFR using the simplified Modification of Diet in Renal Disease Study equation. Mitral annular calcification (MAC), aortic sclerosis, and aortic annular calcification were assessed by two-dimensional echocardiography. Logistic regression was used to examine the odds of valvular calcification among participants with chronic kidney disease (CKD; GFR < 60 ml/min per 1.73 m(2)). A total of 3047 participants (52% women; mean age 59 +/- 10 yr) were available for analysis. CKD was present in 8.6% (n = 262) of the sample. Among participants with valve/annular calcification (n = 284; 9.3%), 20% had CKD, compared with 7% in patients without valvular calcification. After adjustment for age, gender, systolic and diastolic BP, hypertension treatment, total/HDL cholesterol, body mass index, diabetes, smoking status, and cardiovascular disease, participants with CKD had a 60% increased odds of MAC (odds ratio 1.6; 95% confidence interval 1.03 to 2.5). There was no significant association between CKD and either aortic sclerosis or aortic annular calcification (odds ratio 1.1 and 1.1, respectively). After age and gender adjustment, the combination of both CKD and MAC was associated with a three-fold increased risk for death compared with those with neither condition (P = 0.0004). In the community, CKD is associated with presence of MAC before the onset of ESRD. Further research is warranted to understand whether traditional and novel vascular risk factor burden, as well as metabolic derangements found in early kidney disease, can account for the CKD-MAC association.     

Cardiovascular disease in patients with end-stage renal disease on hemodialysis in a developing country

Cardiovascular disease is the main cause of death among patients with end-stage renal disease (ESRD). The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on hemodialysis (HD) in Brazil. Their mean age was 47 ± 39 years. The main risk factors for cardiovascular diseases were arterial hypertension (89.4%), dyslipidemia (78.3%), low high-density lipoprotein levels (84.2%) and low physical activity (64.1%). Family history of coronary insufficiency and high low-density lipoprotein levels were significantly associated with coronary artery disease (P = 0.005 and P = 0.029, respectively). Sedentary life style, diabetes mellitus, secondary hyperparathyroidism and hyperglycemia also showed a significant association with the underlying vascular disease (P = 0.017, P = 0.039, P = 0.037 and P = 0.030, respectively). Hypercalcemia, hypertension and black race were factors significantly associated with left ventricular systolic dysfunction (P = 0.01, P = 0.0013 and P = 0.024, respectively). Our study shows that the most prevalent cardiovascular diseases in patients with ESRD were left ventricular hypertrophy, atherosclerotic disease, valvular disease and coronary artery disease. Hypertension and dyslipidemia were the common risk factors associated with cardiovascular diseases. The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on HD in a single center in Brazil.     

Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease

Cardiovascular mortality is elevated in patients with end-stage renal disease (ESRD), especially in those with diabetes mellitus. Although the higher cardiovascular death rate in diabetic ESRD patients may be the result of more advanced atherosclerotic changes of the arterial wall, this has not been documented previously. Aortic stiffness was compared between ESRD patients with and without diabetes, and the impact of aortic stiffness on cardiovascular mortality was examined in a prospective, observational cohort study. The cohort consisted of 265 ESRD patients on hemodialysis, including 50 diabetic patients studied between June 1992 and December 1998. At baseline, the diabetic ESRD patients had significantly higher aortic pulse wave velocity (PWV), a noninvasive measure of aortic stiffness, than the nondiabetic patients. During a mean follow-up period of 63 mo, 81 deaths, including 36 cardiovascular deaths, were recorded. Kaplan-Meier analysis revealed higher all-cause or cardiovascular mortality rates in the diabetic as compared with the nondiabetic patients and also in those with higher aortic PWV than those with lower aortic PWV. The effect of diabetes on cardiovascular death was significant in the Cox model, including age, years on hemodialysis, gender, smoking, C-reactive protein, hematocrit, and body mass index as covariates. However, when aortic PWV was included as a covariate, the impact of diabetes was no longer significant, whereas aortic PWV was a significant predictor. In a model including 13 covariates, aortic PWV remained a significant predictor for cardiovascular and overall mortality but not for non-cardiovascular death. These results demonstrate that the increased aortic stiffness of the ESRD patients with diabetes mellitus contributed to the higher all-cause and cardiovascular mortality rates.     

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.