Kidney function, cholesterol absorption and remnant lipoprotein accumulation in patients with diabetes mellitus.

AIM: Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. METHODS: The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. RESULTS: The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) µg/mL and 2.3 (1.7-3.0) µg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. CONCLUSIONS: The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.

Antialbuminuric advantage of cilnidipine compared with L-type calcium channel blockers in type 2 diabetic patients with normoalbuminuria and microalbuminuria.

We evaluated the antialbuminuric advantage of cilnidipine, an N/L-type calcium channel blocker (CCB), compared with L-type CCBs in diabetic patients with normoalbuminuria and microalbuminuria. The study was a multicenter, non-randomized crossover trial. Participants were 90 type 2 diabetic patients exhibiting either normo- or microalbuminuria, and undergoing CCB treatment for ≥6 months prior to study entry. The CCB at the time of entry was continued for the first 6 months (Period 1). Treatment was subsequently switched from cilnidipine to an L-type CCB, or vice versa, for the second 6-month observation period (Period 2). During Period 1, the L-type CCB group showed a significant increase of urinary albumin excretion (UAE) over time, while the cilnidipine group showed no significant elevation. During Period 2, switching of the treatment from the L-type CCB to cilnidipine resulted in significant reduction of the UAE, whereas switching from cilnidipine to the L-type CCB resulted in no significant change in the UAE. This study demonstrated that the antialbuminuric effect of Cilnidipine, but not the L-type CCBs, was sustained even in patients treated for a long time. In addition, the antialbuminuric effect can be anticipated after switching from an L-type CCB to cilnidipine, but not vice versa.

Brachial-ankle pulse wave velocity as an index of central arterial stiffness.

AIM: Stiffness of the central arteries plays an important role in the pathophysiology of cardiovascular disease, and pulse wave velocity (PWV) of the aorta has been used as the standard measure of central arterial stiffness. An automated device for brachial-ankle (ba) PWV is available, although information is limited whether baPWV reflects the stiffness of central or peripheral arteries. We therefore addressed this question in the present study. METHODS: The subjects were 2,806 consecutive participants in our non-invasive vascular laboratory, excluding those with an ankle-brachial index (ABI) lower than 0.95. PWV measurements were simultaneously performed using an automated device for the ba, heart-femoral (hf, aorta), heart-carotid (hc), heart-brachial (hb), and femoral-ankle (fa) segments. Correlational analyses were performed (1) among these PWV values, (2) between PWV and individual risk factors, and (3) between PWV and the Framingham risk score (FRS), a surrogate index for integrated cardiovascular risk. RESULTS: The correlation of baPWV was the highest with hfPWV (r=0.796) and the lowest with hcPWV (r=0.541). Among the known factors preferentially affecting central arterial stiffness, higher age, diabetes mellitus, and chronic kidney disease (CKD) were also closely associated with increased baPWV. Finally, FRS was more closely correlated with hfPWV (r=0.613) and baPWV (r=0.609) than with hbPWV (r=0.523), hcPWV (r=0.509), and faPWV (r=0.393). CONCLUSION: These results indicate that baPWV is an index of arterial stiffness showing similar characteristics to those of aortic PWV.

Central versus peripheral arterial stiffness in association with coronary, cerebral and peripheral arterial disease.

BACKGROUND: Although stiffness of central arteries is more preferentially associated with coronary artery disease (CAD) than that of peripheral arteries, less is known for cerebrovascular disease (CVD) and peripheral artery disease (PAD). We measured pulse wave velocity (PWV) in four arterial segments, and examined the relative changes in the four regional PWVs in patients with CAD, CVD or PAD. METHODS: The 2798 subjects were selected from 3300 consecutive participants of our non-invasive vascular lab. 342 subjects had one or more pre-existing atherosclerotic diseases including 128 CAD (N=128), CVD (N=195) and PAD (N=83). PWVs were simultaneously measured using an automated pulse wave analyzer (model BP-203RPE, Colin) in the heart-femoral (hf, aorta), heart-carotid (hc), heart-brachial (hb), and femoral-ankle (fa) segments. RESULTS: As compared to the subjects without atheroscletoric disease, those with CAD, CVD, or PAD showed higher levels of PWV in the four arterial segments, particularly in hfPWV. The relative increase in hfPWV remained significant after adjustment for age, sex, hypertension, pulse rate, smoking, diabetes mellistus, dyslipidemia, and chronic kidney disease. CONCLUSION: This study indicates that the preferential increase in central arterial stiffness is found not only in CAD but CVD and PAD as well.

Plasma angiopoietin-like protein 3 (ANGPTL3) concentration is associated with uremic dyslipidemia.

OBJECTIVE: Angiopoietin-like protein 3, a liver-derived plasma protein, increases plasma triglycerides (TG) in mice by suppressing the activity of lipoprotein lipase, a key enzyme in plasma TG clearance. Uremic dyslipidemia is characterized by increased TG-rich lipoproteins such as very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), lowered high-density lipoprotein (HDL), and TG-enrichment of low-density lipoprotein (LDL) and HDL. Since the role of angiopoietin-like protein 3 (ANGPTL3) in uremic dyslipidemia is unknown, we examined its possible association with the lipoprotein abnormalities in patients with chronic renal failure (CRF). METHODS: The subjects were 202 hemodialysis patients, 44 predialysis patients with CRF and 148 healthy control subjects comparable in age and sex. Fasting plasma ANGPTL3 was measured by enzyme-linked immunoassay, and lipoproteins were fractioned by ultracentrifugation. RESULTS: Median (25th-75th percentile range) ANGPTL3 levels were 523 (409-645) and 393 (308-511)ng/mL in hemodialysis and predialysis patients, respectively, which were significantly lower than the control level of 700 (570-875)ng/mL. In the total subjects, ANGPTL3 was inversely correlated with VLDL- and IDL-cholesterol levels, and positively with HDL-cholesterol. ANGPTL3 correlated inversely with TG/cholesterol ratios of both LDL and HDL. In multiple regression models, these associations, excluding TG/cholesterol ratio of LDL, remained significant and independent of possible confounders including age, sex, body mass index, insulin resistance index (HOMA-IR), and adiponectin, whereas the associations of ANGPTL3 with the lipoprotein parameters were less significant when apoC-II/C-III ratio was included in the models. CONCLUSION: The reduced ANGPTL3 level in hemodialysis patients was consistently associated with the major components of uremic dyslipidemia. ANGPTL3 may be a novel factor contributing to uremic dyslipidemia.

Small dense low-density lipoprotein cholesterol concentration and carotid atherosclerosis.

Low-density lipoprotein cholesterol (LDL-C) and the small dense LDL (SdLDL) phenotype are both predictors for ischemic heart disease. We examined whether cholesterol of SdLDL (SdLDL-C) is more closely associated with carotid artery intima-media thickness (CA-IMT), a surrogate measure of atherosclerosis, than LDL-C and other lipid parameters. The subjects were 326 consecutive participants including those with dyslipidemia, diabetes mellitus, hypertension, chronic kidney disease, and smokers. SdLDL-C was quantified by a newly developed precipitation method, and CA-IMT by high-resolution B-mode ultrasound. In univariate analysis, CA-IMT was most strongly correlated with SdLDL-C (Spearman's r=0.441, P<0.001), followed by apolipoprotein (apo) B, LDL-C, non-high-density lipoprotein cholesterol (Non-HDL-C), and plasma triglycerides (TG). HDL-C and apo A-I correlated inversely with CA-IMT. Non-lipid variables that were associated with CA-IMT were age, sex, presence of diabetes mellitus, presence of hypertension, estimate glomerular filtration rate (eGFR), and C-reactive protein (CRP). Even after adjustment for age, sex, diabetes mellitus, hypertension, smoking, eGFR and CRP, the positive association of CA-IMT with SdLDL-C remained significant, and again stronger than the associations with others lipid parameters. Further analyses revealed that the level of SdLDL-C was elevated in subgroups of the subjects including men, older subjects, smokers, those with higher CRP levels, those with diabetes mellitus, and hypertensive patients. These results indicate that SdLDL-C was the best marker of carotid atherosclerosis among the lipid parameters tested, and suggest that quantitative measurement of SdLDL-C gives useful information in the risk assessment for atherosclerotic disease.

Association between plasma angiopoietin-like protein 3 and arterial wall thickness in healthy subjects.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a liver-derived plasma protein that modulates plasma triglyceride clearance, angiogenesis and atherosclerosis in experimental models. So far, no study has examined its role in atherosclerosis in human subjects. We evaluated the possible association between plasma ANGPTL3 level and carotid artery intima-media thickness (CA-IMT) and femoral artery intima-media thickness (FA-IMT) in healthy human subjects. METHODS: The subjects were 381 healthy volunteers. Plasma ANGPTL3 was determined by a specific ELISA. CA-IMT and FA-IMT were measured by high-resolution B-mode ultrasonography. RESULTS: The plasma ANGPTL3 level was 764 +/- 291 ng/ml (mean +/- SD). CA-IMT showed a significant positive correlation with plasma ANGPTL3 and other classical risk factors such as age, blood pressure, and plasma glucose and lipid levels. The positive association between ANGPTL3 and CA-IMT remained significant after adjustment for age, sex, smoking, body mass index, systolic blood pressure, plasma glucose, insulin resistance index, triglyceride, and high-density and low-density lipoprotein cholesterol levels. ANGPTL3 also showed a positive association with FA-IMT independent of these factors. CONCLUSIONS: These results demonstrate for the first time that ANGPTL3 is closely associated with arterial wall thickness in human subjects.

Regional arterial stiffness in patients with type 2 diabetes and chronic kidney disease.

Increased arterial stiffness is an independent predictor of death from cardiovascular disease, and aortic stiffness is more predictive than stiffness of other arterial regions. Because little is known about the effect of chronic kidney disease (CKD) on regional arterial stiffness, pulse wave velocity (PWV) of four different arterial segments was measured in patients who had type 2 diabetes with and without various stages of CKD. A total of 434 patients had type 2 diabetes, and there were 192 healthy control subjects who were comparable in age and gender. GFR was estimated by the abbreviated Modification of Diet in Renal Disease equation. The patients with diabetes were classified into CKD stages by the definition of the Kidney Disease Outcomes Quality Initiative guidelines. PWV was measured in the heart-femoral, heart-carotid, heart-brachial, and femoral-ankle segments simultaneously using an automatic pulse wave analyzer. PWV of each arterial region was increased in patients who had diabetes without kidney damage and was increased further in a stepwise manner with the advanced stages of CKD. The increase in PWV was greater in the heart-femoral and heart-carotid regions than in the heart-brachial and femoral-ankle segments. However, after adjustment for age, BP, and other confounding factors using a multiple regression model, decreased GFR was independently associated with increased PWV of the heart-femoral region but not with PWV of other arterial segments. In type 2 diabetes, CKD was associated with increased stiffness of arteries, particularly of the aorta. The cross-sectional result may explain the increased risk for cardiovascular disease in CKD, although longitudinal studies are needed to confirm it.

Regional arterial stiffness associated with ischemic heart disease in type 2 diabetes mellitus.

Arterial stiffness is increased in type 2 diabetes mellitus, and diabetes preferentially affects arterial stiffness of the central (elastic, capacitive) over peripheral (muscular, conduit) arteries. We hypothesized that arterial stiffness of the central artery may be more closely associated with ischemic heart disease (IHD) than stiffness of peripheral arteries in type 2 diabetes mellitus. The subjects were 595 type 2 diabetes patients including 70 with IHD. Arterial stiffness was measured as pulse wave velocity (PWV) in the heart-carotid, heart-femoral, heart-brachial, and femoral-ankle regions. The PWV values of the four segments correlated with each other in patients without IHD. However, the correlations were less impressive in those with IHD, suggesting unequal stiffening of regional arteries in IHD. As compared with patients without IHD, the IHD group showed significantly higher PWV values of the four arterial segments, particularly of the heart-femoral region. The presence of IHD was significantly associated with higher heart-femoral PWV, and this association remained significant and independent of other factors in a multiple logistic regression analysis. Pulse pressure was more strongly correlated with PWV of the heart-femoral than other arterial regions. Thus, diabetic patients with IHD have increased stiffness of arteries, particularly of the aorta, supporting the concept that central arterial stiffness plays an important role in the development of IHD.

Effect of atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus.

OBJECTIVE: A statin, a potent lipid-lowering drug, improves pain-free walking distance in patients with peripheral arterial disease (PAD) without increasing the ankle-brachial pressure index (ABI). Arterial stiffness affects the blood flow of peripheral arteries. The purpose of this study was to evaluate the effect of cholesterol-lowering with atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus. METHODS: The subjects were 22 type 2 diabetic patients with hypercholesterolemia, who received atorvastatin at a daily dose of 10 mg for 6 months. Before and after the treatment with atorvastatin, we measured pulse wave velocity (PWV) in the heart-brachial, heart-carotid, heart-femoral and femoral-ankle segments. RESULTS: Following treatment with atorvastatin, femoral-ankle PWV showed a significant reduction. The PWV of other arterial segments tended to decrease, although the changes were not statistically significant. We found no significant changes in blood pressure, heart rate, ABI, or plasma concentrations of glucose, L-arginine and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial function. CONCLUSIONS: Atorvastatin treatment was associated with an improvement in the stiffness of leg arteries in type 2 diabetes mellitus. This may partly explain the statin-mediated improvement of walking performance in those with PAD.

Altered relationship between body fat and plasma adiponectin in end-stage renal disease.

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.

Arterial stiffness in predialysis patients with uremia.

BACKGROUND: Hemodialysis patients have advanced arterial wall stiffening as shown by increased aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. We compared aortic PWV of uremic patients before starting hemodialysis treatment with that of patients on maintenance hemodialysis. METHODS: The subjects were 71 patients with end-stage renal disease (ESRD) before starting hemodialysis (predialysis group), 144 patients on maintenance hemodialysis, and 140 healthy control subjects. These three groups were all nondiabetic and comparable in age and gender. RESULTS: The hemodialysis group had greater aortic PWV than the healthy subjects, and the predialysis patients showed a still higher value than the hemodialysis group. Multiple regression analysis in the total subjects revealed that the presence of renal failure was significantly associated with increased aortic PWV independent of age, gender, blood pressure, body mass index, smoking, high-density lipoprotein (HDL) and nonhigh-density lipoprotein (non-HDL) cholesterol levels. In contrast, hemodialysis was associated with decreased aortic PWV independent of renal failure and the other factors. Further analyses in the combined uremic patients again indicated the favorable impact of hemodialysis on aortic PWV independent of the classical risk factors, use of antihypertensive medications, including angiotensin-converting enzyme inhibitors and calcium channel blockers, hematocrit, serum calcium, phosphorus, parathyroid hormone levels, and the use of calcium carbonate. Insulin resistance using homeostasis model assessment (HOMA-IR) was associated with increased aortic PWV. CONCLUSION: Aortic stiffening was present in uremic patients before starting hemodialysis treatment and no adverse effect of hemodialysis was observed, suggesting the important roles of renal failure and/or metabolic alterations secondary to renal failure in arterial stiffness in patients with uremia.

Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population.

BACKGROUND: Renal failure results in deficiency of active vitamin D3 that has diverse effects on metabolism and organ functions. Treatment with active forms of vitamin D(3) ameliorates abnormalities in bone and mineral metabolism, cardiac function, immune response and others. We hypothesized that treatment with vitamin D(3) may be beneficial for survival in patients with end-stage renal disease (ESRD). METHODS: We compared the risk of death between regular users (n = 162) and non-users (n = 80) of oral 1alpha-hydroxyvitamin D3 (alfacalcidol) in a cohort of ESRD patients undergoing haemodialysis for a follow-up of 61 +/- 23 months. The daily dose of alfacalcidol ranged from 0.25 to 1.5 microg, with a median of 0.5 microg. RESULTS: The alfacalcidol users showed a lower risk of death from cardiovascular disease than the non-users in a univariate Cox model [hazards ratio (HR) 0.287, 95% confidence interval (CI) 0.127-0.649, P = 0.003], whereas the risk for death from non-cardiovascular disease was not different between the two groups. Stepwise multivariate Cox analysis showed that cardiovascular mortality was significantly associated with age, presence of diabetes mellitus and treatment with alfacalcidol (HR 0.377, 95% CI 0.246-0.578, P = 0.022). CONCLUSIONS: These results indicate that use of oral alfacalcidol was associated with reduced risk for cardiovascular death in this cohort of ESRD patients. The result of this observational study warrants further randomized controlled trials with 1alpha-hydroxy vitamin D3 to confirm the possibility that such medication improves survival of ESRD patients.

Pulse wave velocity in lower-limb arteries among diabetic patients with peripheral arterial disease.

OBJECTIVE: Patients with type 2 diabetes mellitus are at an increased risk of atherosclerosis including peripheral arterial disease (PAD). The purpose of this study was to examine the possible alteration in pulse wave velocity (PWV) in lower-limb arteries among diabetic patients with PAD. METHODS: We measured brachial-ankle PWV (baPWV) using an automatic device in 101 healthy control subjects and 102 type 2 diabetic patients including those with PAD. RESULTS: Diabetic patients without PAD showed a higher baPWV than the healthy control subjects. There was no significant difference in baPWV between the right and left legs in these groups. In contrast, among diabetic patients with PAD, baPWV was significantly lower in the affected legs than in the non-affected legs, and the reduction in baPWV was greater in those with lower ankle-brachial pressure index (ABI). In the patients with PAD who received percutaneous transluminal angioplasty, both baPWV and ABI were increased following successful vessel dilatation. CONCLUSIONS: These results suggest that baPWV is increased in diabetic patients, whereas it is decreased in the affected legs in diabetic patients with PAD. Widening of the right-left difference in baPWV may be a novel marker of PAD.

The association of antibodies against oxidized low-density lipoprotein with atherosclerosis in hemodialysis patients.

BACKGROUND: Immune response to oxidized low-density lipoprotein (oxLDL) may modulate atherogenesis. We recently reported that a high titer of serum anti-oxLDL antibody was an independent predictor of a low risk for cardiovascular death in patients with end-stage renal disease (ESRD). In the present study, we examined a possible association between anti-oxLDL antibody titer and arterial wall thickness in ESRD patients. METHODS: The subjects were 103 ESRD patients treated with hemodialysis. A high resolution B-mode ultrasound method was used to measure intima-media thickness of carotid (CA-IMT) and femoral arteries (FA-IMT). RESULTS: In univariate analysis, anti-oxLDL antibody showed a significant negative correlation with FA-IMT. The inverse association between anti-oxLDL antibody and FA-IMT remained significant in multiple regression analysis, including age, gender, blood pressure, plasma lipids, smoking, C-reactive protein, calcium-phosphate product, serum albumin, body mass index, and duration of dialysis as covariates. The antibody titer showed an inverse trend with CA-IMT without statistical significance. CONCLUSION: These results show for the first time that titer of anti-oxLDL antibody is an independent factor inversely associated with arterial thickness in ESRD, supporting the concept that immunity against oxLDL plays an anti-atherogenic role.

Preferential stiffening of central over peripheral arteries in type 2 diabetes.

Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arterial stiffness was evaluated by measuring pulse wave velocity (PWV) in the heart-carotid, heart-brachial, heart-femoral, and femoral-ankle segments using an automatic device. The diabetic patients had greater PWV than the healthy subjects in the four arterial regions, and the effect of diabetes on PWV was greater in the heart-carotid and heart-femoral segments (central) than in the heart-brachial and femoral-ankle regions (peripheral). PWV increased with age in the four arterial regions, and the effect of age on PWV was greater in the central than in peripheral arteries. In multiple regression analysis, age and systolic blood pressure had significant impacts on PWV of the four regions, whereas diabetes was significantly associated only with PWV of the central arteries. In contrast, sex was associated with PWV of the peripheral arteries. Thus, type 2 diabetes had greater impact on PWV of the central arteries, and different factors were involved in PWV among different arterial regions.

Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease.

BACKGROUND: Immune response to oxidized low-density lipoprotein (oxLDL) may modulate the process of atherogenesis and cardiovascular disease. METHODS: We performed a prospective, observational cohort study in 249 patients with end-stage renal disease (ESRD) to examine whether the serum titer of anti-oxLDL antibody can predict cardiovascular mortality. RESULTS: The median anti-oxLDL antibody titer was 320 mU/mL at baseline. During the follow-up (63 +/- 23 months), 72 deaths including 34 cardiovascular deaths occurred. When the subjects were divided into two groups by the median titer, the high titer group showed a lower risk for cardiovascular mortality (P = 0.040 by Kaplan-Meier analysis and log-rank test). Multivariate Cox proportional hazards model indicated that the lower risk of cardiovascular death in the high titer group remained significant (hazard ratio of 0.46, 95%CI 0.23-0.95, P = 0.037) and independent of age, presence of vascular complications, presence of diabetes mellitus, and elevated C-reactive protein. In contrast, anti-oxLDL antibody titer was not associated with non-cardiovascular mortality. CONCLUSIONS: These results demonstrate, to our knowledge for the first time, that serum anti-oxLDL antibody titer is an independent predictor of cardiovascular mortality in a cohort of patients with ESRD.

Advanced atherosclerosis in predialysis patients with chronic renal failure.

BACKGROUND: Atherosclerosis is advanced in hemodialysis patients as shown by increased intima-media thickness of carotid arteries (CA-IMT), although it is not established whether the advanced atherosclerosis results from hemodialysis treatment or from chronic renal failure. The purpose of this study was to evaluate the effects of hemodialysis and renal failure on CA-IMT in patients with chronic renal failure. METHODS: CA-IMT was measured by high-resolution B-mode ultrasonography in 110 patients with chronic renal failure before starting dialysis (CRF group), and compared with CA-IMT of 345 hemodialysis patients (HD group) and 302 healthy control subjects. They were all nondiabetic and the three groups were comparable in age and gender. RESULTS: As compared with the healthy control subjects, the CRF and HD groups had greater CA-IMTs, whereas CA-IMTs of the CRF and HD groups were not statistically different. There was no significant correlation between duration of hemodialysis and CA-IMT in the HD group. Multiple regression analysis in the total subjects indicated that presence of renal failure, but not being treated with hemodialysis, was a significant factor associated with increased CA-IMT independent of age, gender, blood pressure, smoking, high-density lipoprotein (HDL) and non-HDL cholesterol levels. CONCLUSIONS: These results demonstrate that thickening of arterial wall is present in patients with chronic renal failure before starting hemodialysis treatment, and support the concept that advanced atherosclerosis in hemodialysis patients is due not to hemodialysis treatment, but to renal failure and/or metabolic abnormalities secondary to renal failure.

Effect of diabetes on uremic dyslipidemia.

Elevated intermediate-density lipoprotein (IDL), a remnant lipoprotein, is an independent risk factor for atherosclerosis in patients with end-stage renal disease (ESRD). Since the presence of diabetes mellitus further increases the risk of cardiovascular mortality in ESRD, we examined the effect of diabetes on IDL among ESRD patients. The subjects were 330 healthy control subjects and 287 patients with end-stage renal disease including 80 patients with type 2 diabetes. As compared with the healthy subjects, the nondiabetic ESRD patients had increased plasma triglyceride and IDL cholesterol. Diabetic patients with ESRD showed a further increase in plasma triglyceride and IDL cholesterol compared with the nondiabetic group. However, the difference in IDL levels between the ESRD groups was no longer significant when subjects were stratified by plasma triglyceride. Plasma triglyceride was correlated with IDL cholesterol. Increased hemoglobin A(1c) was significantly associated with IDL cholesterol in a multiple regression model including age, gender, and the presence of ESRD. Such an association was no longer significant in another model including plasma triglyceride as an additional covariate. Further analysis indicated the positive effects of diabetes and hyperglycemia on plasma triglyceride. These results indicate that increased IDL in ESRD is further deteriorated in the presence of diabetes, and that the adverse effect is accounted for at least partly by hypertriglyceridemia associated with chronic hyperglycemia.