Cardiovascular calcification in patients with chronic renal failure: are we on target with this risk factor?

End-stage renal disease (ESRD) is comprised of conditions associated with metabolic disorders associated with soft tissue and coronary artery calcification (CAC). The most consistent determinants of CAC in these patients are extent and duration of renal dysfunction and older age. The majority of published studies have not found a causal relationship between measures of calcium-phosphorus balance and CAC. When taken into consideration, the lipid profile [primarily low high-density lipoprotein cholesterol, elevated triglycerides, elevated low-density lipoprotein (LDL-C), and elevated total cholesterol] are important factors in the calcification process. Recent data seems to indicate that CAC is regulated both positively and negatively by a wide variety of mechanisms affecting patients with renal disease. The progression of CAC can be reduced from a 25% to 30% to 0% to 6% annual increase with LDL-C reduction caused by statins or possibly sevelamer. It is currently unclear whether the calcium-phosphorus balance and its related treatments are involved in CAC progression in ESRD patients. Further research into the determinants and potential treatments for CAC in association with ESRD is warranted.     

Thirty-month follow-up of coronary artery calcification in hemodialysis patients: different roles for inflammation and abnormal calcium-phosphorous metabolism?

BACKGROUND: Cardiovascular disease is the leading cause of death in hemodialysis (HD) patients. Coronary artery calcification (CAC) is considered a marker of atherosclerosis and coronary artery disease (CAD). The CAC progression and factors that influence it were evaluated during a 30-month period. METHODS: Forty HD patients without a history of CAD were enrolled into the study. CAC score was assessed with conventional CT repeated every six months. The circulating factors of phosphorous, calcium, calcium-phosphorous product, intact parathyroid hormone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, lipoprotein-alpha, albumin, high sensitivity C-reactive protein, and fibrinogen were measured monthly. Hypertension and calcium intake during the study period were taken into account as well. RESULTS: At baseline, CAC score was correlated with age and duration of HD therapy. From all evaluated factors, CAC initiation was influenced only by older age and C-reactive protein. CAC, when it was started, was aggravated continuously and was influenced only by elevated serum phosphorous and calcium-phosphorous product. Hypertension, lipid profile, and calcium intake did not affect CAC initiation or progression. CONCLUSIONS: Once CAC progression starts, it is an uninterrupted process. The roles of inflammation and abnormal calcium-phosphorous metabolism in CAC differ. Inflammation is the major factor that contributes in CAC initiation. Elevated serum phosphorous and calcium-phosphorous product accelerates CAC progression.     

Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study

The objective of this is study was to examine whether estimated insulin resistance and insulin resistance-related factors are associated with coronary artery calcification (CAC) in 1,420 asymptomatic participants in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. A total of 656 patients with type 1 diabetes and 764 control subjects aged 20-55 years were examined. CAC was assessed by electron-beam computed tomography. Insulin resistance was computed with linear regression based on an equation previously validated in clamp studies on type 1 diabetic adults. Insulin resistance was associated with CAC (OR 1.6 in type 1 diabetes and 1.4 in control subjects, P < 0.001), independent of coronary artery disease risk factors. There was a male excess of CAC in control subjects (OR 2.7, adjusted for age, smoking, and LDL and HDL cholesterol levels) and in type 1 diabetic patients (OR 2.2, adjusted for the same factors and diabetes duration). After adjusting for insulin resistance, the CAC male excess in diabetic patients decreased from OR 2.2 (P < 0.001) to 1.8 (P = 0.04). After adjustment for waist-to-hip ratio, waist circumference, or visceral fat, the gender difference in CAC was not significant in diabetic subjects. In conclusion, gender differences in insulin resistance-associated fat distribution may explain why type 1 diabetes increases coronary calcification in women relatively more than in men.     

冠状动脉钙化对维持性血液透析患者心脏结构和功能的影响及其相关因素评估

目的 观察冠状动脉钙化（CAC）对维持性血液透析（MHD）患者心脏结构和功能的影响，探讨引起CAC的相关危险因素。 方法 40例MHD患者经螺旋CT扫描，了解合并CAC的患者比例，并计算其钙化积分以评估CAC程度。应用心脏彩超和颈动脉超声检查心脏形态、功能及颈动脉斑块，进一步分析MHD患者各项临床指标与CAC的关系。 结果 25例MHD患者（62.5%）合并不同程度的CAC，平均钙化积分为672.3。钙化组（CAC组）与无钙化组（NCAC组）心脏形态及左室顺应性、颈动脉内膜中层厚度（IMT）、斑块发生率、斑块积分差异均有统计学意义。缺血性心脏病和心衰竭发生率均以CAC组为高。4例死于心脏疾病患者均存在CAC。颈动脉斑块阳性组IMT平均为（0.86±0.15） mm，钙化发生率为81%，冠状动脉钙化积分为867±198，均明显高于斑块阴性组[分别为（0.73±0.14） mm,42%,437±176,P < 0.05]。CAC组年龄、糖尿病或肥胖患者比例、透析时间、血磷、C反应蛋白（CRP）、胆固醇和低密度脂蛋白水平、钙磷乘积、颈动脉IMT、斑块积分均高于NCAC组。多元逐步回归分析显示，年龄、透析时间与CAC密切相关。 结论 MHD患者普遍存在CAC。CAC与心脏结构、功能的变化及颈动脉粥样硬化相关。糖尿病及肥胖患者比例、钙磷代谢及脂代谢异常、透析时间、CRP、动脉粥样硬化是CAC的相关因素。年龄和透析时间是CAC的独立危险因素。     

The association of bone density and calcified atherosclerosis is stronger in women without dyslipidemia: The multi‐ethnic study of atherosclerosis

We tested whether the association between bone mineral density (BMD) and coronary artery calcification (CAC) varies according to dyslipidemia in community‐living individuals. Between 2002 and 2005, 305 women and 631 men (mean age of 64 years), who were not taking lipid‐lowering medications or estrogen were assessed for spine BMD, CAC, and total (TC), HDL‐ and LDL‐cholesterol and triglycerides. Participants were a random sample from the Multi‐Ethnic Study of Atherosclerosis (MESA) without clinical cardiovascular disease. Spine BMD at the L3 vertebrate was performed by computer tomography (CT). CAC prevalence was measured by CT. The total cholesterol to HDL ratio (TC:HDL) ≥ 5.0 was used as the primary marker of hyperlipidemia. The association of BMD with CAC differed in women with TC:HDL < 5.0 versus higher (p‐interaction = 0.01). In age‐ and race‐adjusted models, among women with TC:HDL < 5.0, each SD (43.4 mg/cc) greater BMD was associated with a 25% lower prevalence of CAC (prevalence ratio [PR] 0.75, 95% confidence interval [CI] 0.63–0.89), whereas among women with higher TC:HDL, higher BMD was not significantly associated with CAC (PR 1.22, 95% CI 0.82–1.82). Results were similar using other definitions of hyperlipidemia. In contrast, no consistent association was observed between BMD and CAC in men, irrespective of the TC:HDL ratio (p interaction 0.54). The inverse association of BMD with CAC is stronger in women without dyslipidemia. These data argue against the hypothesis that dyslipidemia is the key factor responsible for the inverse association of BMD with atherosclerosis. © 2011 American Society for Bone and Mineral Research     

Are the Anticardiolipin Antibodies a Risk Factor for Coronary Artery Disease in Chronic Renal Failure Patients?

Objective. It has been proposed that anticardiolipin (aCL) antibodies are a risk factor for coronary artery disease (CAD) in recently studies. In this study, we aimed to investigate the existence of coronary artery disease in dialysis patients who were aCL positive and undergoing hemodialysis and peritoneal dialysis due to end stage renal failure and also to determine its relationship with risk factors in patients with coronary artery disease. Methods. This study has been conducted in the end stage renal failure in 140 hemodialysis patients, 18 peritoneal dialysis patients, and 38 healthy controls. The urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin values are obtained. In all cases, aCL levels are investigated with ELISA method. Results. In the HD and CAPD patients, no significant relationship could be found between the age, gender, dialysis time, total cholesterol, HDL cholesterol, LDL cholesterol, total protein, and albumin values (p > 0.05). HD and CAPD vs. controls (aCL), 9.2% (13/140), 11.1% (2/18) vs. 2.6% (1/38), p = 0.002. No significant difference was noted between aCL-positive and -negative patients in serum urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin levels. The coronary artery disease was determined in three patients out of 16 patients with aCL positivity. Conclusion. The prevalence of aCL antibodies positivity in our study was similar to the prevalence of aCL positivity in other studies. Therefore, we do not think aCL antibodies positivity is a risk factor for coronary artery disease.     

Early Subclinical Coronary Artery Calcification in Young Adults Who Were Pediatric Kidney Transplant Recipients

Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality.     

Abnormal glucose tolerance and lipid abnormalities in Indian myocardial infarct survivors

Glucose tolerance and lipid levels in a random sample of 103 Indian patients (96 males and 7 females) with coronary artery disease (CAD) aged between 20 and 55 years were compared with those in a healthy Indian control group matched as regards age and sex. Previous episodes of myocardial infarction were taken as evidence of CAD. Of the patients 44% were overweight. Glucose tolerance was abnormal in 55% of the patients. Both cholesterol and triglyceride values in the patients with CAD were significantly higher than those in the control group. Serum cholesterol levels were over 6,5 mmol/l in 62% of the patients with CAD and serum triglyceride levels were over 2,0 mmol/l in .53%. Males with CAD tended to have lower plasma high-density lipoprotein (HDL) cholesterol levels than the control group (P less than 0,01). There was a significant negative correlation between body mass index and HDL cholesterol, and no correlation was demonstrated between body mass index and total cholesterol or triglyceride levels. Furthermore, when the patients were sub-grouped according to their glucose tolerances it was found that only the triglyceride levels were significantly different (values were higher in those with abnormal glucose tolerance). Our data suggest that abnormal glucose tolerance and lipid aberrations are significant risk factors in Indian patients with CAD.     

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

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

Apolipoprotein B but not LDL Cholesterol Is Associated With Coronary Artery Calcification in Type 2 Diabetic Whites

OBJECTIVE

Evidence favors apolipoprotein B (apoB) over LDL cholesterol as a predictor of cardiovascular events, but data are lacking on coronary artery calcification (CAC), especially in type 2 diabetes, where LDL cholesterol may underestimate atherosclerotic burden. We investigated the hypothesis that apoB is a superior marker of CAC relative to LDL cholesterol.

RESEARCH DESIGN AND METHODS

We performed cross-sectional analyses of white subjects in two community-based studies: the Penn Diabetes Heart Study (N = 611 type 2 diabetic subjects, 71.4% men) and the Study of Inherited Risk of Coronary Atherosclerosis (N = 803 nondiabetic subjects, 52.8% men) using multivariate analysis of apoB and LDL cholesterol stratified by diabetes status.

RESULTS

In type 2 diabetes, apoB was associated with CAC after adjusting for age, sex, and medications [Tobit regression ratio of increased CAC for 1-SD increase in apoB; 1.36 (95% CI 1.06–1.75), P = 0.016] whereas LDL cholesterol was not [1.09 (0.85–1.41)]. In nondiabetic subjects, both were associated with CAC [apoB 1.65 (1.38–1.96), P < 0.001; LDL cholesterol 1.56 (1.30–1.86), P < 0.001]. In combined analysis of diabetic and nondiabetic subjects, apoB provided value in predicting CAC scores beyond LDL cholesterol, total cholesterol, the total cholesterol/HDL cholesterol and triglyceride/HDL cholesterol ratios, and marginally beyond non-HDL cholesterol.

CONCLUSIONS

Plasma apoB, but not LDL cholesterol, levels were associated with CAC scores in type 2 diabetic whites. ApoB levels may be particularly useful in assessing atherosclerotic burden and cardiovascular risk in type 2 diabetes.Apolipoprotein B (apoB) may be more useful clinically than LDL cholesterol in coronary heart disease (CHD) because it captures greater information about atherogenic particles and is not influenced by heterogeneity of particle cholesterol content (1). Measurement of LDL cholesterol is relatively insensitive to the accumulation of small, dense LDL particles, which are believed to be highly atherogenic (1). This is reflected in the preponderance of evidence from prospective epidemiologic studies and statin trials favoring apoB over LDL cholesterol as a predictor of cardiovascular risk as well as residual risk on statin therapy (2–10).Heterogeneity of LDL particle cholesterol content is increased in type 2 diabetes because insulin resistance drives VLDL cholesterol production, leading to depletion of LDL cholesterol via the action of cholesterol ester transfer protein (CETP) (11). CETP exchanges triglycerides for cholesterol on LDL particles, which are remodeled by lipases to produce cholesterol-poor, small, dense LDL particles (11,12). Because there is one apoB per LDL particle, regardless of density, apoB detects the presence of these atherogenic particles, in contrast to LDL cholesterol, and thus may be better suited to guide lipid-lowering therapy, particularly in insulin resistance and type 2 diabetes.Data are lacking on the relationship of apoB to coronary artery calcification (CAC), a quantitative measure of sub-clinical atherosclerosis and predictor of CHD in diabetes (13) as well as in the general population (14,15). Therefore, we examined the relative association of plasma apoB and LDL cholesterol with CAC in two cross-sectional studies of individuals without known CHD, one recruited based on type 2 diabetes and the other based on family history of CHD. We hypothesized that apoB levels would be stronger predictors of CAC than LDL cholesterol levels, particularly in type 2 diabetic subjects. We also hypothesized that apoB might add incremental value to traditional cholesterol-based CHD risk parameters.     

Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women

We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.     

The value of computed tomography-derived coronary artery calcification score in coronary artery disease detection in asymptomatic hemodialysis patients

BACKGROUND: We evaluated the value of coronary artery calcification (CAC) score in coronary artery disease (CAD) detection in asymptomatic hemodialysis (HD) patients by evaluating the association among CAC score, exercise electrocardiography (EECG), and Thallium-201 dipyridamole scintigraphy. Correlation between aortic pulse wave velocity (PWV) and CAC score was also evaluated. METHODS: CAC score was assessed with conventional computed tomography in 40 patients. Thirty patients completed EECG and 25; those with a positive CAC score and/or a positive EECG performed Thallium dipyridamole scintigraphy. Carotid-femoral PWV was assessed in all patients. RESULTS: There was no association among CAC score and EECG or Thallium dipyridamole scintigraphy. In contrast, CAC score was correlated with aortic PWV. CONCLUSION: The previous results question the role of CAC score in the detection of CAD in asymptomatic HD patients. The correlation between CAC score and aortic PWV raises the possibility that CAC score represents more an indicator of coronary artery medial wall calcification than a marker of CAD.     

The Value of Computed Tomography-Derived Coronary Artery Calcification Score in Coronary Artery Disease Detection in Asymptomatic Hemodialysis Patients

Background. We evaluated the value of coronary artery calcification (CAC) score in coronary artery disease (CAD) detection in asymptomatic hemodialysis (HD) patients by evaluating the association among CAC score, exercise electrocardiography (EECG), and Thallium-201 dipyridamole scintigraphy. Correlation between aortic pulse wave velocity (PWV) and CAC score was also evaluated. Methods. CAC score was assessed with conventional computed tomography in 40 patients. Thirty patients completed EECG and 25; those with a positive CAC score and/or a positive EECG performed Thallium dipyridamole scintigraphy. Carotid-femoral PWV was assessed in all patients. Results. There was no association among CAC score and EECG or Thallium dipyridamole scintigraphy. In contrast, CAC score was correlated with aortic PWV. Conclusion. The previous results question the role of CAC score in the detection of CAD in asymptomatic HD patients. The correlation between CAC score and aortic PWV raises the possibility that CAC score represents more an indicator of coronary artery medial wall calcification than a marker of CAD.     

Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.     

A common promoter polymorphism in the hepatic lipase gene (LIPC-480C>T) is associated with an increase in coronary calcification in type 1 diabetes

Type 1 diabetes is associated with coronary heart disease (CHD) and coronary artery calcification (CAC), a measure of subclinical CHD. The hepatic lipase gene promoter polymorphism (LIPC-480C>T) is a common variant affecting lipid metabolism. This study examined the relation between the LIPC-480C>T and CAC in type 1 diabetes. In the type 1 diabetic patients studied, 56% had CAC >0 Agatston units (AU). These subjects had a longer duration of diabetes (26.2 +/- 1.3 vs. 17.8 +/- 1.4 years; P < 0.001), lower HDL cholesterol levels (55.7 +/- 2.4 vs. 61.0 +/- 2.5 mg/dl; P = 0.05), higher triglyceride levels (101 +/- 17.3 vs. 66 +/- 7.6 mg/dl; P < 0.05), and higher diastolic blood pressure (79.7 +/- 1.0 vs. 76.0 +/- 1.4 mmHg; P < 0.05). The LIPC-480 T allele was more common in subjects with CAC (frequency = 0.31 +/- 0.05 vs. 0.14 +/- 0.04; P = 0.006). The proportion with CAC was 44% in LIPC-480CC subjects, 71% in heterozygotes, and 83% in LIPC-480TT subjects (P < 0.01). LIPC-480 T allele frequency increased as the amount of CAC increased (P = 0.007). LIPC-480 genotype was independently associated with the CAC (odds ratio = 2.90, 95% CI 1.22-6.92, P < 0.05) after adjusting for duration of diabetes, age, sex, diastolic blood pressure, HDL cholesterol, and triglyceride levels. In conclusion, the LIPC-480C>T polymorphism was associated with subclinical CHD in type 1 diabetes. This genetic variant may identify subjects in which early intervention to prevent CHD may be appropriate.     

Serum malondialdehyde and coronary artery disease in hemodialysis patients

BACKGROUND/AIMS: It has been suggested that enhanced oxidative stress participates in the acceleration of coronary artery disease (CAD) in patients with end-stage renal disease (ESRD). The aim of this study was to investigate the relationship between the level of malondialdehyde (MDA), which is a marker of lipid peroxidation, and the severity of CAD in ESRD patients. METHODS: We conducted a study of 39 hemodialysis patients (median age 58 years; 27 males and 12 females; diabetics 44%). In these patients, the predialysis serum concentrations of MDA and C-reactive protein (CRP) were measured. We performed multirow spiral computed tomography to derive coronary artery calcification (CAC) scores, as a marker of CAD severity. RESULTS: Eleven of the 39 patients had minimal CAC (28%, CAC score <10), 10 patients had mild to moderate CAC (26%, 10-400), and 18 patients had severe CAC (46%, >400). The MDA levels increased (p < 0.05) with increasing CAC category and were correlated (r = 0.35, p < 0.05) with the CAC scores. The levels of MDA also correlated with the serum concentrations of CRP and albumin (r = 0.34, p < 0.05 and r = -0.32, p < 0.05, respectively). Patients in the highest tertile of MDA compared with the other patients were over four times as likely to have severe CAC, and the highest tertile of MDA was an independent predictor of severe CAC, along with a previous cardiovascular event. CONCLUSION: An increased level of MDA, which was associated with inflammatory markers, was a predictive factor for severe CAC in ESRD patients.     

Cardiovascular risk factors in predialysis patients: baseline data from the Chronic Renal Impairment in Birmingham (CRIB) study

BACKGROUND: Patients with end-stage kidney failure have a greatly increased risk of developing premature cardiac and vascular disease. However, little is known about the evolution of cardiovascular diseases in individuals with less severely impaired kidney function. METHODS: The prevalence of cardiovascular diseases and of suspected cardiovascular risk factors was studied in a group of 369 individuals (median age, 63 years, 67% male) with various degrees of impaired kidney function (calculated creatinine clearances 6 to 105 mL/min), in 103 patients with angiographically proven coronary artery disease, and in 103 apparently healthy individuals. These patients are being followed prospectively. RESULTS: Of those patients with kidney disease, 34% had a history of vascular disease and 21% had left ventricular hypertrophy on electrocardiogram at baseline. Traditional risk factors were prevalent, with a history of hypertension in 76% of kidney disease patients, diabetes in 15%, and dyslipidemia with reduced low-density lipoprotein (LDL) cholesterol, elevated serum triglycerides, and decreased high-density lipoprotein (HDL) levels. Other possible cardiovascular risk factors include elevated concentrations of plasma homocysteine, as well as low serum albumin and hemoglobin levels. Patients with more severely impaired renal function had lower diastolic blood pressures, lower LDL and HDL cholesterol levels, were more anemic, and had higher plasma homocysteine concentrations. CONCLUSIONS: Vascular disease and left ventricular hypertrophy are prevalent among patients with chronic kidney disease not requiring dialysis. In addition to traditional risk factors, other features of the uremic syndrome such as anemia, hyperhomocysteinemia, and inflammation (suggested by hypoalbuminemia) may contribute.     

Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes

We evaluated correlates of coronary atherosclerosis, measured by coronary artery calcium, in a racially diverse group of male and female subjects with type 2 diabetes. Age, systolic blood pressure, sex, and race/ethnicity were significant determinants of coronary artery calcium. Among lipoproteins, cholesterol level contained in a particle excluded from direct measures of LDL and HDL cholesterol (designated triglyceride-rich lipoprotein cholesterol) was most strongly linked to coronary artery calcium. Neither inflammatory markers nor metabolic factors correlated with coronary artery calcium in models adjusted for age and sex, but measures of adipose distribution did. Waist-to-hip ratio and the ratio of visceral to total abdominal tissue were positively associated with coronary artery calcium. In fully adjusted multivariate models, the relationship of adiposity measures to coronary artery calcium was no longer significant after inclusion of apolipoprotein B or triglyceride-rich lipoprotein cholesterol. Traditional risk factors and race/ethnicity remain important correlates of coronary artery calcium in a cohort at elevated risk of cardiovascular disease because of type 2 diabetes. Adiposity measures are significantly associated with coronary artery calcium score, but their importance may be largely explained by apolipoprotein B or triglyceride-rich lipoprotein cholesterol.     

Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: Causes of Dysregulation of Lipid Metabolism in Chronic Renal Failure

End‐stage renal disease (ESRD) is associated with accelerated atherosclerosis and premature death from cardiovascular disease. These events are driven by oxidative stress inflammation and lipid disorders. ESRD‐induced lipid abnormalities primarily stem from dysregulation of high‐density lipoprotein (HDL), triglyceride‐rich lipoprotein metabolism, and oxidative modification of lipoproteins. In this context, production and plasma concentration of Apo‐I and Apo‐II are reduced, HDL maturation is impaired, HDL composition is altered, HDL antioxidant and anti‐inflammatory functions are depressed, clearance of triglyceride‐rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentration is elevated in ESRD. The associated defect in HDL maturation is largely caused by acquired lecithin‐cholesterol acyltransferase deficiency while its triglyceride enrichment is due to hepatic lipase deficiency. Hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride‐rich lipoproteins and their remnants are mediated by down‐regulation of lipoprotein lipase, hepatic lipase, very low‐density lipoprotein (VLDL) receptor, and LDL receptor‐related protein, relative reduction in ApoC‐II/ApoC‐III ratio, up‐regulation of acyl‐CoA cholesterol acyltransferase, and elevated plasma level of cholesterol ester‐poor prebeta HDL. Impaired clearance and accumulation of oxidation‐prone VLDL and chylomicron remnants and abnormal LDL composition in the face of oxidative stress and inflammation favors their uptake by macrophages and resident cells in the artery wall. The effect of heightened influx of lipids is compounded by impaired HDL‐mediated reverse cholesterol transport leading to foam cell formation which is the central event in atherosclerosis plaque formation and subsequent plaque rupture, thrombosis, and tissue damage.     

Low-density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end-stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low-density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n = 30) and peritoneal dialysis patients (PD; n = 17), and compared them to 40 asymptomatic, non-uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.